#sen2geneID pmid senID geneID hgncID approvedSymbol matchString actualString startPos score flankingText matchCodeID tag SciMinerVersion SciMinerMethod inExClude inExCludeCond phenotypeOnly conflictCode hgncIDbyNR NRText editTag editUser oldGeneID oldHgncID oldApprovedSymbol oldInExClude oldInExCludeCond 302977 1853774 437050 20996 11179 SOD1 ALS ALS 2 0.0 Autoimmunity and ALS a comparison of animal models of immune-mediated motor neuron destruction 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00105796358040523<>ScoreDetail__5468|IGFALS|0__11179|SOD1|0.00105796358040523__ 0 0 0 0 0 302978 1853774 437050 20996 11179 SOD1 ALS ALS 15 0.0 of animal models of immune-mediated motor neuron destruction and human ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00105796358040523<>ScoreDetail__5468|IGFALS|0__11179|SOD1|0.00105796358040523__ 0 0 0 0 0 303364 2241118 438230 9353 4931 HLA-A MHC MHC 10 1.5 expression of class I and II major histocompatibility complex (MHC) MHC antigens was seen in the affected areas of spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 303365 2241118 438231 9353 4931 HLA-A MHC MHC 1 1.5 New MHC expression was concentrated in phagocytes particularly in degenerating white matter 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 303366 2241118 438232 9353 4931 HLA-A MHC MHC 0 1.5 MHC antigen was not revealed in motor neurons or skeletal muscle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 303367 2241118 438235 9353 4931 HLA-A MHC MHC-restricted 16 1.5 cell-mediated activity in the affected areas rather than an ongoing MHC-restricted T-cell response 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 303408 2263315 438324 20996 11179 SOD1 ALS ALS 20 0.0 a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), ALS the cellular composition of the spinal cord inflammatory infiltrate was 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000967484540195492<>ScoreDetail__5468|IGFALS|0.00016220600162206__11179|SOD1|0.000967484540195492__ 0 0 0 0 0 303409 2263315 438324 20996 11179 SOD1 ALS ALS 37 0.0 cord inflammatory infiltrate was analysed in eight cases of sporadic ALS by a panel of monoclonal antibodies 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000967484540195492<>ScoreDetail__5468|IGFALS|0.00016220600162206__11179|SOD1|0.000967484540195492__ 0 0 0 0 0 303410 2263315 438327 9353 4931 HLA-A MHC MHC 12 1.5 ALS specimens exhibited an increase in major histocompatibility complex (MHC) MHC products or human leucocyte antigens (HLA) HLA in the corticospinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 303411 2263315 438327 20996 11179 SOD1 ALS ALS 3 0.0 Compared to controls ALS specimens exhibited an increase in major histocompatibility complex (MHC) MHC 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000967484540195492<>ScoreDetail__5468|IGFALS|0.00016220600162206__11179|SOD1|0.000967484540195492__ 0 0 0 0 0 303412 2263315 438330 20996 11179 SOD1 ALS ALS 15 0.0 autoimmune process or infectious agent may play a role in ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000967484540195492<>ScoreDetail__5468|IGFALS|0.00016220600162206__11179|SOD1|0.000967484540195492__ 0 0 0 0 0 305218 3719465 443416 20996 11179 SOD1 ALS ALS 15 0.0 with clinical and pathological resemblance to amyotrophic lateral sclerosis (ALS) ALS in a woman who was severely bitten on the ankle 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000712567808872135<>ScoreDetail__5468|IGFALS|0.000413166230546757__11179|SOD1|0.000712567808872135__ 0 0 0 0 0 305219 3719465 443418 20996 11179 SOD1 ALS ALS 9 0.0 A number of unusual features that are uncharacteristic of ALS were found that included a markedly elevated antinuclear antibody titre 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000712567808872135<>ScoreDetail__5468|IGFALS|0.000413166230546757__11179|SOD1|0.000712567808872135__ 0 0 0 0 0 305220 3719465 443419 20996 11179 SOD1 ALS ALS 16 0.0 anterior horn cells and pyramidal degeneration that are characteristic of ALS but an extraordinary finding was the presence of transmural granulomatous 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000712567808872135<>ScoreDetail__5468|IGFALS|0.000413166230546757__11179|SOD1|0.000712567808872135__ 0 0 0 0 0 305242 3772394 443573 3893 1682 CD47 IAP IAP 6 0.0 Significant increase in immunosuppressive acidic protein (IAP) IAP in serum of patients with multiple sclerosis and other inflammatory 1 JUMiner_v2.2 1 0 0 2 5329 TotalCon:4<>1682|CD47|961|Complete__5329|IAPP|3375|Complete__28880|MAGT1|84061|Complete__437|ALPI|248|Complete__<>AvaiableGeneRif=4<>BEST:5329|IAPP|0.000490780818649671<>ScoreDetail__437|ALPI|0.000436800436800437__1682|CD47|0.000449349104605828__5329|IAPP|0.000490780818649671__28880|MAGT1|0.000235017626321974__ 0 0 0 0 0 305243 3772394 443574 3893 1682 CD47 IAP IAP 0 0.0 IAP a type of alpha 1-acid glycoprotein is mainly produced by 1 JUMiner_v2.2 1 0 0 2 5329 TotalCon:4<>1682|CD47|961|Complete__5329|IAPP|3375|Complete__28880|MAGT1|84061|Complete__437|ALPI|248|Complete__<>AvaiableGeneRif=4<>BEST:5329|IAPP|0.000490780818649671<>ScoreDetail__437|ALPI|0.000436800436800437__1682|CD47|0.000449349104605828__5329|IAPP|0.000490780818649671__28880|MAGT1|0.000235017626321974__ 0 0 0 0 0 305244 3772394 443575 3893 1682 CD47 IAP IAP 6 0.0 We assayed the serum levels of IAP by a single radial immunodiffusion method 1 JUMiner_v2.2 1 0 0 2 5329 TotalCon:4<>1682|CD47|961|Complete__5329|IAPP|3375|Complete__28880|MAGT1|84061|Complete__437|ALPI|248|Complete__<>AvaiableGeneRif=4<>BEST:5329|IAPP|0.000490780818649671<>ScoreDetail__437|ALPI|0.000436800436800437__1682|CD47|0.000449349104605828__5329|IAPP|0.000490780818649671__28880|MAGT1|0.000235017626321974__ 0 0 0 0 0 305245 3772394 443576 3893 1682 CD47 IAP IAP 4 0.0 The normal level of IAP is below 500 micrograms/ml micrograms ml (385 385 -73 . 1 JUMiner_v2.2 1 0 0 2 5329 TotalCon:4<>1682|CD47|961|Complete__5329|IAPP|3375|Complete__28880|MAGT1|84061|Complete__437|ALPI|248|Complete__<>AvaiableGeneRif=4<>BEST:5329|IAPP|0.000490780818649671<>ScoreDetail__437|ALPI|0.000436800436800437__1682|CD47|0.000449349104605828__5329|IAPP|0.000490780818649671__28880|MAGT1|0.000235017626321974__ 0 0 0 0 0 305246 3772394 443577 3893 1682 CD47 IAP IAP 5 0.0 In multiple sclerosis patients however IAP increased during exacerbation (630 630 -191 and decreased during the 1 JUMiner_v2.2 1 0 0 2 5329 TotalCon:4<>1682|CD47|961|Complete__5329|IAPP|3375|Complete__28880|MAGT1|84061|Complete__437|ALPI|248|Complete__<>AvaiableGeneRif=4<>BEST:5329|IAPP|0.000490780818649671<>ScoreDetail__437|ALPI|0.000436800436800437__1682|CD47|0.000449349104605828__5329|IAPP|0.000490780818649671__28880|MAGT1|0.000235017626321974__ 0 0 0 0 0 305247 3772394 443578 3893 1682 CD47 IAP IAP 12 0.0 of patients with neuro-Behcet's disease also had high levels of IAP correlating well with disease activity 1 JUMiner_v2.2 1 0 0 2 5329 TotalCon:4<>1682|CD47|961|Complete__5329|IAPP|3375|Complete__28880|MAGT1|84061|Complete__437|ALPI|248|Complete__<>AvaiableGeneRif=4<>BEST:5329|IAPP|0.000490780818649671<>ScoreDetail__437|ALPI|0.000436800436800437__1682|CD47|0.000449349104605828__5329|IAPP|0.000490780818649671__28880|MAGT1|0.000235017626321974__ 0 0 0 0 0 305248 3772394 443579 3893 1682 CD47 IAP IAP 10 0.0 In some patients with Guillain-Barre syndrome or Miller Fisher syndrome IAP increased during the acute phase 1 JUMiner_v2.2 1 0 0 2 5329 TotalCon:4<>1682|CD47|961|Complete__5329|IAPP|3375|Complete__28880|MAGT1|84061|Complete__437|ALPI|248|Complete__<>AvaiableGeneRif=4<>BEST:5329|IAPP|0.000490780818649671<>ScoreDetail__437|ALPI|0.000436800436800437__1682|CD47|0.000449349104605828__5329|IAPP|0.000490780818649671__28880|MAGT1|0.000235017626321974__ 0 0 0 0 0 305249 3772394 443580 3893 1682 CD47 IAP IAP 6 0.0 In patients with herpes simplex encephalitis IAP levels remained abnormally high for more than 60 days after 1 JUMiner_v2.2 1 0 0 2 5329 TotalCon:4<>1682|CD47|961|Complete__5329|IAPP|3375|Complete__28880|MAGT1|84061|Complete__437|ALPI|248|Complete__<>AvaiableGeneRif=4<>BEST:5329|IAPP|0.000490780818649671<>ScoreDetail__437|ALPI|0.000436800436800437__1682|CD47|0.000449349104605828__5329|IAPP|0.000490780818649671__28880|MAGT1|0.000235017626321974__ 0 0 0 0 0 305250 3772394 443581 3893 1682 CD47 IAP IAP 4 0.0 The mean value of IAP in patients with amyotrophic lateral sclerosis did not differ from 1 JUMiner_v2.2 1 0 0 2 5329 TotalCon:4<>1682|CD47|961|Complete__5329|IAPP|3375|Complete__28880|MAGT1|84061|Complete__437|ALPI|248|Complete__<>AvaiableGeneRif=4<>BEST:5329|IAPP|0.000490780818649671<>ScoreDetail__437|ALPI|0.000436800436800437__1682|CD47|0.000449349104605828__5329|IAPP|0.000490780818649671__28880|MAGT1|0.000235017626321974__ 0 0 0 0 0 305251 3772394 443582 3893 1682 CD47 IAP IAP 3 0.0 An increase in IAP in the serum of patients seems to reflect the activity 1 JUMiner_v2.2 1 0 0 2 5329 TotalCon:4<>1682|CD47|961|Complete__5329|IAPP|3375|Complete__28880|MAGT1|84061|Complete__437|ALPI|248|Complete__<>AvaiableGeneRif=4<>BEST:5329|IAPP|0.000490780818649671<>ScoreDetail__437|ALPI|0.000436800436800437__1682|CD47|0.000449349104605828__5329|IAPP|0.000490780818649671__28880|MAGT1|0.000235017626321974__ 0 0 0 0 0 298691 7783760 427455 3930 7203 CD200 MRC MRC 12 0.0 side of these patients 26 movements were graded by the MRC scale and 20 muscles were assessed by CT imaging 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 299693 7836946 429575 10480 5962 IL10 IL-10 IL-10 4 2.3 Intrathecal synthesis of interleukin-10 (IL-10) IL-10 in viral and inflammatory diseases of the central nervous system 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 299694 7836946 429576 10480 5962 IL10 IL-10 IL-10 6 2.3 The intrathecal synthesis of interleukin 10 (IL-10) IL-10 was investigated in 120 paired cerebrospinal fluid (CSF) CSF and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 299695 7836946 429576 11629 6493 LAMC2 CSF CSF 14 0.0 (IL-10) IL-10 was investigated in 120 paired cerebrospinal fluid (CSF) CSF and serum specimens from patients with various inflammatory and non-inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 299696 7836946 429577 10480 5962 IL10 IL-10 IL-10 0 2.3 IL-10 was not demonstrated in the sera but detectable levels were 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 299697 7836946 429577 10480 5962 IL10 IL-10 IL-10 61 2.3 CNS and a patient with encephalomeningeal sarcoidosis (in in whom IL-10 was demonstrated in all CSF collected over a period of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 299698 7836946 429577 11629 6493 LAMC2 CSF CSF 14 0.0 in the sera but detectable levels were found in the CSF from patients with acute viral ("aseptic") aseptic meningitis but only 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 299699 7836946 429577 11629 6493 LAMC2 CSF CSF 66 0.0 encephalomeningeal sarcoidosis (in in whom IL-10 was demonstrated in all CSF collected over a period of 6-months 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 299700 7836946 429578 10480 5962 IL10 IL-10 IL-10 4 2.3 In chronic meningeal infections/inflammations, infections inflammations IL-10 seems to be continuously produced within the CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 299701 7836946 429578 11629 6493 LAMC2 CSF CSF 12 0.0 infections inflammations IL-10 seems to be continuously produced within the CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 299702 7836946 429579 10480 5962 IL10 IL-10 IL-10 4 2.3 Our findings suggest that IL-10 a cytokine which exerts many immunosuppressive actions may play different 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 301842 8493864 434066 10453 6008 IL2RA CD25 CD25 5 1.0 T cells were negative for CD25 CD54 and major histocompatibility complex (MHC)-class MHC -class II 1 JUMiner_v2.2 1 0 0 2 6008 TotalCon:2<>6008|IL2RA|3559|Complete__6130|ISG20|3669|Complete__<>AvaiableGeneRif=2<>BEST:6008|IL2RA|0.00208698340719365<>ScoreDetail__6130|ISG20|0__6008|IL2RA|0.00208698340719365__ 0 0 0 0 0 301843 8493864 434066 9808 5344 ICAM1 CD54 CD54 6 1.0 T cells were negative for CD25 CD54 and major histocompatibility complex (MHC)-class MHC -class II 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 301844 8493864 434066 9353 4931 HLA-A MHC MHC 11 1.5 were negative for CD25 CD54 and major histocompatibility complex (MHC)-class MHC -class II 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 301845 8493864 434069 9353 4931 HLA-A MHC MHC 1 1.5 Increased MHC class II expression was present on denervated Schwann cells and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 297398 8605177 424638 20997 11180 SOD2 MnSOD MnSOD 4 1.9 Human manganese superoxide dismutase (MnSOD) MnSOD is a homotetrameric enzyme which protects mitochondria against oxygen-mediated free 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 297399 8605177 424641 20997 11180 SOD2 MnSOD MnSOD 12 1.9 A crystallographic structure of the naturally occurring polymorphic variant Ile58Thr MnSOD reveals that the helical hairpin mutation Thr58 causes two packing 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 297400 8605177 424643 20997 11180 SOD2 MnSOD MnSOD 1 1.9 Ile58Thr MnSOD is primarily dimeric in solution and is significantly less thermostable 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 297401 8605177 424644 20997 11180 SOD2 MnSOD MnSOD 3 1.9 Consequently this mutant MnSOD is compromised at normal body temperatures thermal inactivation predicted from 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 297402 8605177 424644 20997 11180 SOD2 MnSOD MnSOD 44 1.9 at 41 degrees C compared with 3.1 years for native MnSOD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 297403 8605177 424645 20997 11180 SOD2 MnSOD MnSOD 23 1.9 3 h has no effect on the activity of native MnSOD but completely inactivates mutant MnSOD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 297404 8605177 424645 20997 11180 SOD2 MnSOD MnSOD 28 1.9 on the activity of native MnSOD but completely inactivates mutant MnSOD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 297405 8605177 424646 20997 11180 SOD2 MnSOD MnSOD 4 1.9 Rapid inactivation of Ile58Thr MnSOD at the elevated temperatures associated with fever and inflammation could 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 297548 8737921 424888 20996 11179 SOD1 ALS ALS 3 0.0 Amyotrophic lateral sclerosis (ALS) ALS resembles the spongiform encephalopathies in its dual pattern of inherited 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000975314771371629<>ScoreDetail__5468|IGFALS|0.000301346012187772__11179|SOD1|0.000975314771371629__ 0 0 0 0 0 297549 8737921 424890 20996 11179 SOD1 ALS ALS 22 0.0 fresh-frozen within three hours of death from a case of ALS or a control case 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000975314771371629<>ScoreDetail__5468|IGFALS|0.000301346012187772__11179|SOD1|0.000975314771371629__ 0 0 0 0 0 297550 8737921 424896 20996 11179 SOD1 ALS ALS 12 0.0 of our carefully-controlled experiment suggest that it is unlikely that ALS is caused by a scrapie-like agent capable of transmission to 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000975314771371629<>ScoreDetail__5468|IGFALS|0.000301346012187772__11179|SOD1|0.000975314771371629__ 0 0 0 0 0 296744 9086508 423597 14373 7808 NGF NGF NGF 8 1.2 Neurotrophic factors (NTFs) NTFs such as nerve growth factor (NGF), NGF brain-derived neurotrophic factor (BDNF) BDNF and ciliary neurotrophic factor (CNTF) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 296745 9086508 423597 1624 1033 BDNF BDNF BDNF 12 1.9 as nerve growth factor (NGF), NGF brain-derived neurotrophic factor (BDNF) BDNF and ciliary neurotrophic factor (CNTF) CNTF are currently being explored 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 296746 9086508 423597 4649 2169 CNTF CNTF CNTF 17 1.9 brain-derived neurotrophic factor (BDNF) BDNF and ciliary neurotrophic factor (CNTF) CNTF are currently being explored as novel therapeutics in a range 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 296747 9086508 423597 9947 5468 IGFALS ALS ALS 36 0.3 range of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) ALS and Alzheimer's disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0005967342053518<>ScoreDetail__5468|IGFALS|0.000510948905109489__11179|SOD1|0.0005967342053518__ 0 0 0 0 0 296748 9086508 423599 14373 7808 NGF NGF NGF 5 1.2 It is apparent that both NGF and BDNF induce a range of adverse effects for example 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 296749 9086508 423599 1624 1033 BDNF BDNF BDNF 7 1.9 It is apparent that both NGF and BDNF induce a range of adverse effects for example inflammation hyperalgesia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 296750 9086508 423600 14373 7808 NGF NGF NGF 5 1.2 It has been demonstrated that NGF induces release of biologically active mediators such as histamine from 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 296751 9086508 423603 1624 1033 BDNF BDNF BDNF 21 1.9 manner in response to NTFs with a rank order of BDNF > CNTF > NGF in contrast RPMC were refractory to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 296752 9086508 423603 4649 2169 CNTF CNTF CNTF 23 1.9 response to NTFs with a rank order of BDNF > CNTF > NGF in contrast RPMC were refractory to the effects 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 296753 9086508 423603 14373 7808 NGF NGF NGF 25 1.2 NTFs with a rank order of BDNF > CNTF > NGF in contrast RPMC were refractory to the effects of BDNF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 296754 9086508 423603 1624 1033 BDNF BDNF BDNF 35 1.9 NGF in contrast RPMC were refractory to the effects of BDNF and CNTF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 296755 9086508 423603 4649 2169 CNTF CNTF CNTF 37 1.9 contrast RPMC were refractory to the effects of BDNF and CNTF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 292700 9270568 415805 20996 11179 SOD1 ALS ALS 8 0.0 Chamorros suffer from two neurologic syndromes known as ALS and the parkinsonism-dementia complex (PDC) PDC of Guam 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00053555337403539<>ScoreDetail__5468|IGFALS|0.000279665520038035__11179|SOD1|0.00053555337403539__ 0 0 0 0 0 292701 9270568 415805 16271 8759 PDC PDC PDC 13 0.0 neurologic syndromes known as ALS and the parkinsonism-dementia complex (PDC) PDC of Guam 1 JUMiner_v2.2 1 0 0 2 9153 TotalCon:2<>8759|PDC|5132|Complete__9153|PNKD|25953|Complete__<>AvaiableGeneRif=2<>BEST:9153|PNKD|0.00106923282544774<>ScoreDetail__8759|PDC|0__9153|PNKD|0.00106923282544774__ 0 0 0 0 0 292702 9270568 415810 16271 8759 PDC PDC PDC 5 0.0 Twelve cases were diagnosed as PDC known locally as bodig and three as ALS known locally 1 JUMiner_v2.2 1 0 0 2 9153 TotalCon:2<>8759|PDC|5132|Complete__9153|PNKD|25953|Complete__<>AvaiableGeneRif=2<>BEST:9153|PNKD|0.00106923282544774<>ScoreDetail__8759|PDC|0__9153|PNKD|0.00106923282544774__ 0 0 0 0 0 292703 9270568 415810 20996 11179 SOD1 ALS ALS 13 0.0 diagnosed as PDC known locally as bodig and three as ALS known locally as lytico. 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00053555337403539<>ScoreDetail__5468|IGFALS|0.000279665520038035__11179|SOD1|0.00053555337403539__ 0 0 0 0 0 293253 9339959 416950 5010 2434 CSF2 GM-CSF GM-CSF 8 2.2 Haemopoietic growth factors like granulocyte-macrophage colony stimulating factor (GM-CSF) GM-CSF or interleukin-3 prevent apoptosis in target cells and modulation of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288339 9562310 408233 10463 6018 IL6 IL-6 IL-6 2 1.3 We assayed IL-6 in 105 cerebrospinal fluid (CSF) CSF samples from patients with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288340 9562310 408233 11629 6493 LAMC2 CSF CSF 7 1.0 We assayed IL-6 in 105 cerebrospinal fluid (CSF) CSF samples from patients with ALS MS HTLV-1 associated myelopathy (HAM), 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288341 9562310 408233 9947 5468 IGFALS ALS ALS 12 0.3 in 105 cerebrospinal fluid (CSF) CSF samples from patients with ALS MS HTLV-1 associated myelopathy (HAM), HAM and controls 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288342 9562310 408234 10463 6018 IL6 IL-6 IL-6 5 1.3 There was considerable overlap in IL-6 levels in all patient groups 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288343 9562310 408235 10463 6018 IL6 IL-6 IL-6 2 1.3 The mean IL-6 in 27 patients with ALS was significantly higher than in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288344 9562310 408235 9947 5468 IGFALS ALS ALS 7 0.3 The mean IL-6 in 27 patients with ALS was significantly higher than in 21 patients in the other 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288345 9562310 408237 11629 6493 LAMC2 CSF CSF 1 1.0 Overall CSF IL-6 correlated with protein concentration but not with percentage IgG 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288346 9562310 408237 10463 6018 IL6 IL-6 IL-6 2 1.3 Overall CSF IL-6 correlated with protein concentration but not with percentage IgG or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288347 9562310 408238 11629 6493 LAMC2 CSF CSF 2 1.0 Patients with CSF oligoclonal bands were no more likely to have detectable IL-6 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288348 9562310 408238 10463 6018 IL6 IL-6 IL-6 12 1.3 CSF oligoclonal bands were no more likely to have detectable IL-6 than patients without oligoclonal bands 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288349 9562310 408239 10463 6018 IL6 IL-6 IL-6 1 1.3 Similarly IL-6 did not correlate with clinical disease activity in MS when 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288350 9562310 408240 10463 6018 IL6 IL-6 IL-6 2 1.3 The elevated IL-6 in ALS may reflect an ongoing humoral immune response or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288351 9562310 408240 9947 5468 IGFALS ALS ALS 4 0.3 The elevated IL-6 in ALS may reflect an ongoing humoral immune response or IL-6 may 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288352 9562310 408240 10463 6018 IL6 IL-6 IL-6 13 1.3 in ALS may reflect an ongoing humoral immune response or IL-6 may be non-specifically expressed in these patients as a putative 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288353 9562310 408243 10463 6018 IL6 IL-6 IL-6 0 1.3 IL-6 is a B cell differentiation factor that was first described 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288354 9562310 408246 11629 6493 LAMC2 CSF CSF 2 1.0 Cerebrospinal fluid (CSF) CSF levels of IL-6 are consistently elevated in herpes simplex virus 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288355 9562310 408246 10463 6018 IL6 IL-6 IL-6 5 1.3 Cerebrospinal fluid (CSF) CSF levels of IL-6 are consistently elevated in herpes simplex virus encephalitis and other 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288356 9562310 408248 10463 6018 IL6 IL-6 IL-6 0 1.3 IL-6 was detected in experimental allergic encephalomyelitis CSF ( Gijbels et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288357 9562310 408248 11629 6493 LAMC2 CSF CSF 7 1.0 IL-6 was detected in experimental allergic encephalomyelitis CSF ( Gijbels et al. 1990 and systemic lupus erythematosus with 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288358 9562310 408248 10463 6018 IL6 IL-6 IL-6 30 1.3 central nervous system involvement ( Hirohata and Miyamoto 1990 but IL-6 was not detected in multiple sclerosis (MS) MS ( Houssiau 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288359 9562310 408249 10463 6018 IL6 IL-6 IL-6 2 1.3 Reports of IL-6 in non-inflammatory CNS disease prompted the present study of CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288360 9562310 408249 11629 6493 LAMC2 CSF CSF 12 1.0 IL-6 in non-inflammatory CNS disease prompted the present study of CSF in patients with amyotrophic lateral sclerosis (ALS) ALS 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288361 9562310 408249 9947 5468 IGFALS ALS ALS 19 0.3 study of CSF in patients with amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288362 9562310 408250 10463 6018 IL6 IL-6 IL-6 11 1.3 found a higher frequency of detection and higher levels of IL-6 in ALS than in the other neurological disease control group 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288363 9562310 408250 9947 5468 IGFALS ALS ALS 13 0.3 higher frequency of detection and higher levels of IL-6 in ALS than in the other neurological disease control group 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288364 9562310 408251 11629 6493 LAMC2 CSF CSF 8 1.0 In contrast there was no significant difference in CSF IL-6 in either MS or HAM patients compared to other 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288365 9562310 408251 10463 6018 IL6 IL-6 IL-6 9 1.3 In contrast there was no significant difference in CSF IL-6 in either MS or HAM patients compared to other neurological 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288366 9562310 408251 11629 6493 LAMC2 CSF CSF 28 1.0 other neurological disease controls and there was no correlation of CSF immune parameters and IL-6 levels 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288367 9562310 408251 10463 6018 IL6 IL-6 IL-6 32 1.3 and there was no correlation of CSF immune parameters and IL-6 levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288368 9562310 408252 11629 6493 LAMC2 CSF CSF 8 1.0 These results are consistent with the hypothesis that CSF IL-6 in ALS has an non-immune origin occurring as a 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288369 9562310 408252 10463 6018 IL6 IL-6 IL-6 9 1.3 These results are consistent with the hypothesis that CSF IL-6 in ALS has an non-immune origin occurring as a neurotrophic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288370 9562310 408252 9947 5468 IGFALS ALS ALS 11 0.3 results are consistent with the hypothesis that CSF IL-6 in ALS has an non-immune origin occurring as a neurotrophic response to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288371 9562310 408257 9947 5468 IGFALS ALS ALS 5 0.3 Diagnostic criteria used were for ALS ( Mulder 1982 MS ( Poser et al. 1983 and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288372 9562310 408258 9947 5468 IGFALS ALS ALS 2 0.3 All 19 ALS patients from Japan had progressive weakness without significant sensory disturbance 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288373 9562310 408259 11629 6493 LAMC2 CSF CSF 1 1.0 Eight CSF ALS samples and two non-neurological disease controls were obtained from 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288374 9562310 408259 9947 5468 IGFALS ALS ALS 2 0.3 Eight CSF ALS samples and two non-neurological disease controls were obtained from the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288375 9562310 408260 11629 6493 LAMC2 CSF CSF 28 1.0 HTLV-1 fluorescein antibody titers in serum (1:160-2560) 1 160-2560 and CSF (1:2-64) 1 2-64 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288376 9562310 408261 11629 6493 LAMC2 CSF CSF 1 1.0 Eleven CSF samples were from patients previously reported ( Ohbo et al. 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288377 9562310 408264 11629 6493 LAMC2 CSF CSF 0 1.0 CSF assays 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288378 9562310 408265 10463 6018 IL6 IL-6 IL-6 1 1.3 The IL-6 dependent hybridoma cell line MH6OBSF2 ( Matsuda et al. 1988 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288379 9562310 408268 10463 6018 IL6 IL-6 IL-6 1 1.3 Without IL-6 in the media no viable cells remained in this subclone 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288380 9562310 408272 10463 6018 IL6 IL-6 IL-6 0 1.3 IL-6 was quantitated by reference to a dose calibration curve of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288381 9562310 408272 10463 6018 IL6 IL-6 IL-6 13 1.3 by reference to a dose calibration curve of recombinant human IL-6 (kindly kindly supplied by Drs Hirano and Kishimoto assayed with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288382 9562310 408272 11629 6493 LAMC2 CSF CSF 31 1.0 assayed with MH6OBSF2 cells under the same conditions as the CSF samples 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288383 9562310 408273 11629 6493 LAMC2 CSF CSF 0 1.0 CSF samples were coded and assayed in a blinded fashion 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288384 9562310 408274 11629 6493 LAMC2 CSF CSF 0 1.0 CSF IL-6 values were expressed as log 1 0 pg/ml pg 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288385 9562310 408274 10463 6018 IL6 IL-6 IL-6 1 1.3 CSF IL-6 values were expressed as log 1 0 pg/ml pg ml 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288386 9562310 408275 10463 6018 IL6 IL-6 IL-6 3 1.3 The sensitivity of IL-6 detection was determined to be 1.6 pg/ml pg ml 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288387 9562310 408276 10437 5992 IL1B IL-1 IL-1 16 1.3 showing no mitogenic response with other recombinant human cytokines (IL-1 IL-1 IL-1_amp_#x3b2 IL-2 TNF and abrogating the IL-6 effect by anti-IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288388 9562310 408276 10452 6001 IL2 IL-2 IL-2 19 1.3 mitogenic response with other recombinant human cytokines (IL-1 IL-1 IL-1_amp_#x3b2 IL-2 TNF and abrogating the IL-6 effect by anti-IL-6 polyclonal antibody 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288389 9562310 408276 10463 6018 IL6 IL-6 IL-6 25 1.3 human cytokines (IL-1 IL-1 IL-1_amp_#x3b2 IL-2 TNF and abrogating the IL-6 effect by anti-IL-6 polyclonal antibody (Genzyme, Genzyme Boston MA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288390 9562310 408276 22551 11892 TNF TNF TNF 20 0.2 response with other recombinant human cytokines (IL-1 IL-1 IL-1_amp_#x3b2 IL-2 TNF and abrogating the IL-6 effect by anti-IL-6 polyclonal antibody (Genzyme, 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288391 9562310 408277 11629 6493 LAMC2 CSF CSF 6 1.0 IgG and albumin in sera and CSF were measured by electro-immunoassay ( Tibbling et al. 1977 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288392 9562310 408278 11629 6493 LAMC2 CSF CSF 7 1.0 IgG index was determined by the quotient CSF IgG/serum IgG serum IgG divided by the quotient CSF albumin/serum 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288393 9562310 408278 11629 6493 LAMC2 CSF CSF 14 1.0 quotient CSF IgG/serum IgG serum IgG divided by the quotient CSF albumin/serum albumin serum albumin 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288394 9562310 408283 11629 6493 LAMC2 CSF CSF 9 1.0 The Student t -test was used for comparison of CSF white blood cell count protein IgG %IgG and IgG index 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288395 9562310 408284 10463 6018 IL6 IL-6 IL-6 12 1.3 boundary of detectability of 1.6 pg/ml pg ml for the IL-6 assay (or or log 1 0 IL-6 of 0.2 non-parametric 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288396 9562310 408284 10463 6018 IL6 IL-6 IL-6 18 1.3 ml for the IL-6 assay (or or log 1 0 IL-6 of 0.2 non-parametric techniques were used 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288397 9562310 408289 11629 6493 LAMC2 CSF CSF 3 1.0 Table 1 shows CSF of patients in the ALS MS HAM and OND groups 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288398 9562310 408289 9947 5468 IGFALS ALS ALS 8 0.3 Table 1 shows CSF of patients in the ALS MS HAM and OND groups 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288399 9562310 408292 10463 6018 IL6 IL-6 IL-6 11 1.3 As shown in Fig 1 there was considerable overlap in IL-6 levels in all patient groups 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288400 9562310 408294 10463 6018 IL6 IL-6 IL-6 3 1.3 Table 2 shows IL-6 detection in 78% of 27 patients with ALS (median median 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288401 9562310 408294 9947 5468 IGFALS ALS ALS 11 0.3 2 shows IL-6 detection in 78% of 27 patients with ALS (median median log 1 0 IL-6 of 1.01 55% of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288402 9562310 408294 10463 6018 IL6 IL-6 IL-6 16 1.3 of 27 patients with ALS (median median log 1 0 IL-6 of 1.01 55% of 20 patients with MS (median median 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288403 9562310 408295 11629 6493 LAMC2 CSF CSF 12 1.0 the non-parametric Wilcoxon rank-sum test showed a significant difference in CSF IL-6 between the ALS and OND group ( P =0.0075 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288404 9562310 408295 10463 6018 IL6 IL-6 IL-6 13 1.3 non-parametric Wilcoxon rank-sum test showed a significant difference in CSF IL-6 between the ALS and OND group ( P =0.0075 but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288405 9562310 408295 9947 5468 IGFALS ALS ALS 16 0.3 test showed a significant difference in CSF IL-6 between the ALS and OND group ( P =0.0075 but no significant difference 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288406 9562310 408296 9947 5468 IGFALS ALS ALS 1 0.3 The ALS MS and HAM groups all had statistically significant higher mean 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288407 9562310 408296 10463 6018 IL6 IL-6 IL-6 12 1.3 MS and HAM groups all had statistically significant higher mean IL-6 levels than the non-neurological disease control P _amp_#x3c 0.0001 for 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288408 9562310 408296 9947 5468 IGFALS ALS ALS 23 0.3 than the non-neurological disease control P _amp_#x3c 0.0001 for the ALS group P =0.03 for the MS group and P =0.03 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288409 9562310 408297 11629 6493 LAMC2 CSF CSF 2 1.0 The greatest CSF IL-6 level in the ALS group (log log 1 0 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288410 9562310 408297 10463 6018 IL6 IL-6 IL-6 3 1.3 The greatest CSF IL-6 level in the ALS group (log log 1 0 IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288411 9562310 408297 9947 5468 IGFALS ALS ALS 7 0.3 The greatest CSF IL-6 level in the ALS group (log log 1 0 IL-6 of 2.55 was a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288412 9562310 408297 10463 6018 IL6 IL-6 IL-6 12 1.3 IL-6 level in the ALS group (log log 1 0 IL-6 of 2.55 was a sample from the National Neurological Research 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288413 9562310 408298 9947 5468 IGFALS ALS ALS 14 0.3 is arbitrarily omitted the Wilcoxon rank-sum test P value for ALS vs OND changes very little from P =0.0075 to 0.0118 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288414 9562310 408299 10463 6018 IL6 IL-6 IL-6 9 1.3 Although these results failed to show a higher mean IL-6 level in patients with recognized immune-mediated CNS disease (MS MS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288415 9562310 408300 10463 6018 IL6 IL-6 IL-6 3 1.3 To determine if IL-6 varies with the activity of immune-mediated disease data from the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288416 9562310 408301 11629 6493 LAMC2 CSF CSF 10 1.0 The results in Fig 2 show no significant difference in CSF IL-6 levels with 7 of 12 patients in relapse having 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288417 9562310 408301 10463 6018 IL6 IL-6 IL-6 11 1.3 results in Fig 2 show no significant difference in CSF IL-6 levels with 7 of 12 patients in relapse having detectable 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288418 9562310 408301 10463 6018 IL6 IL-6 IL-6 22 1.3 levels with 7 of 12 patients in relapse having detectable IL-6 compared to 4 of 8 patients with MS in remission 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288419 9562310 408303 11629 6493 LAMC2 CSF CSF 4 1.0 Fig 3 summarizes the CSF results 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288420 9562310 408304 11629 6493 LAMC2 CSF CSF 6 1.0 Oligoclonal bands were present in the CSF only during the relapses and there was an increase in 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288421 9562310 408305 11629 6493 LAMC2 CSF CSF 2 1.0 Despite these CSF changes consistent with fluctuating immune-mediated activity in the CNS the 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288422 9562310 408305 11629 6493 LAMC2 CSF CSF 13 1.0 changes consistent with fluctuating immune-mediated activity in the CNS the CSF IL-6 levels remained at undetectable levels in all four spinal 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288423 9562310 408305 10463 6018 IL6 IL-6 IL-6 14 1.3 consistent with fluctuating immune-mediated activity in the CNS the CSF IL-6 levels remained at undetectable levels in all four spinal taps 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288424 9562310 408306 11629 6493 LAMC2 CSF CSF 6 1.0 To evaluate further any correlation of CSF IL-6 with the extent of immune-mediated activity in the CNS 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288425 9562310 408306 10463 6018 IL6 IL-6 IL-6 7 1.3 To evaluate further any correlation of CSF IL-6 with the extent of immune-mediated activity in the CNS CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288426 9562310 408306 11629 6493 LAMC2 CSF CSF 17 1.0 IL-6 with the extent of immune-mediated activity in the CNS CSF parameters were compared in patients with and without detectable IL-6 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288427 9562310 408306 10463 6018 IL6 IL-6 IL-6 27 1.3 CSF parameters were compared in patients with and without detectable IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288428 9562310 408307 10463 6018 IL6 IL-6 IL-6 12 1.3 a significantly higher total IgG in MS patients with detectable IL-6 levels (not not shown but this correlation was not seen 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288429 9562310 408308 9947 5468 IGFALS ALS ALS 8 0.3 Similarly the percent IgG was higher in the ALS group with detectable IL-6 but not in the combined patient 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288430 9562310 408308 10463 6018 IL6 IL-6 IL-6 12 1.3 percent IgG was higher in the ALS group with detectable IL-6 but not in the combined patient group (not not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288431 9562310 408309 11629 6493 LAMC2 CSF CSF 6 1.0 Table 3 summarizes correlation studies of CSF parameters combining data from all four neurological disease groups (ALS, 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288432 9562310 408309 9947 5468 IGFALS ALS ALS 16 0.3 parameters combining data from all four neurological disease groups (ALS, ALS MS HAM and OND 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288433 9562310 408310 11629 6493 LAMC2 CSF CSF 2 1.0 Only total CSF protein was significantly higher in patients with detectable IL-6 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288434 9562310 408310 10463 6018 IL6 IL-6 IL-6 11 1.3 total CSF protein was significantly higher in patients with detectable IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288435 9562310 408311 11629 6493 LAMC2 CSF CSF 7 1.0 As shown in Table 3 mean CSF protein in patients with detectable IL-6 was 49.0_amp_#xb1 3.8 compared 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288436 9562310 408311 10463 6018 IL6 IL-6 IL-6 13 1.3 in Table 3 mean CSF protein in patients with detectable IL-6 was 49.0_amp_#xb1 3.8 compared to 33.2_amp_#xb1 3.0 in patients with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288437 9562310 408311 10463 6018 IL6 IL-6 IL-6 23 1.3 49.0_amp_#xb1 3.8 compared to 33.2_amp_#xb1 3.0 in patients with undetectable IL-6 ( P _amp_#x3c 0.01 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288438 9562310 408312 11629 6493 LAMC2 CSF CSF 3 1.0 Fig 4 shows CSF IL-6 levels in 35 patients with MS or HAM who 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288439 9562310 408312 10463 6018 IL6 IL-6 IL-6 4 1.3 Fig 4 shows CSF IL-6 levels in 35 patients with MS or HAM who had 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288440 9562310 408312 11629 6493 LAMC2 CSF CSF 20 1.0 MS or HAM who had either oligoclonal bands in the CSF (14 14 patients or did not have oligoclonal bands (21 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288441 9562310 408313 10463 6018 IL6 IL-6 IL-6 2 1.3 Although the IL-6 level was slightly higher in patients without oligoclonal bands and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288442 9562310 408313 10463 6018 IL6 IL-6 IL-6 17 1.3 in patients without oligoclonal bands and the percentage of detectable IL-6 was higher (67% 67% versus 43% these differences were not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288443 9562310 408316 11629 6493 LAMC2 CSF CSF 9 1.0 We found a modest but statistically significant elevation of CSF IL-6 in ALS patients ( Fig 1 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288444 9562310 408316 10463 6018 IL6 IL-6 IL-6 10 1.3 We found a modest but statistically significant elevation of CSF IL-6 in ALS patients ( Fig 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288445 9562310 408316 9947 5468 IGFALS ALS ALS 12 0.3 a modest but statistically significant elevation of CSF IL-6 in ALS patients ( Fig 1 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288446 9562310 408317 9947 5468 IGFALS ALS ALS 13 0.3 using this same assay technique found no difference between 15 ALS patient and 20 controls with psychiatric or neurodegenerative disease ( 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288447 9562310 408318 9947 5468 IGFALS ALS ALS 8 0.3 In comparing these studies a similar percentage of ALS patients had undetectable CSF IL-6 (6/27 6 27 versus 2/15); 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288448 9562310 408318 11629 6493 LAMC2 CSF CSF 12 1.0 these studies a similar percentage of ALS patients had undetectable CSF IL-6 (6/27 6 27 versus 2/15); 2 15 but 37% 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288449 9562310 408318 10463 6018 IL6 IL-6 IL-6 13 1.3 studies a similar percentage of ALS patients had undetectable CSF IL-6 (6/27 6 27 versus 2/15); 2 15 but 37% of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288450 9562310 408318 10463 6018 IL6 IL-6 IL-6 23 1.3 versus 2/15); 2 15 but 37% of our patients had IL-6 levels greater than 10 pg/ml pg ml compared to only 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288451 9562310 408319 10463 6018 IL6 IL-6 IL-6 1 1.3 The IL-6 levels in ALS CSF (less less than 0.96 log 10 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288452 9562310 408319 9947 5468 IGFALS ALS ALS 4 0.3 The IL-6 levels in ALS CSF (less less than 0.96 log 10 pg/ml) pg ml 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288453 9562310 408319 11629 6493 LAMC2 CSF CSF 5 1.0 The IL-6 levels in ALS CSF (less less than 0.96 log 10 pg/ml) pg ml were 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288454 9562310 408320 3890 11935 CD40LG IGM IgM 4 0.3 We did not measure IgM antibodies to GM1 or GDla gangliosides 14 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288455 9562310 408321 9947 5468 IGFALS ALS ALS 16 0.3 the serum of up to 78% of patients with classical ALS ( Pestronk et al. 1989 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288456 9562310 408322 9947 5468 IGFALS ALS ALS 13 0.3 no data to incriminate antiganglioside antibodies in the pathogenesis of ALS and empiric immunosuppressive treatment of patients with motor neuron syndromes 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288457 9562310 408323 10463 6018 IL6 IL-6 IL-6 3 1.3 Nevertheless the modest IL-6 elevation noted here may be related to an ongoing humoral 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288458 9562310 408323 9947 5468 IGFALS ALS ALS 20 0.3 to an ongoing humoral immune response in some patients with ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288459 9562310 408324 10463 6018 IL6 IL-6 IL-6 1 1.3 Serum IL-6 was not measured in ALS but prior studies have shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288460 9562310 408324 9947 5468 IGFALS ALS ALS 6 0.3 Serum IL-6 was not measured in ALS but prior studies have shown that IL-6 can concentrate in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288461 9562310 408324 10463 6018 IL6 IL-6 IL-6 13 1.3 not measured in ALS but prior studies have shown that IL-6 can concentrate in the CSF compartment (e.g e.g during active 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288462 9562310 408324 11629 6493 LAMC2 CSF CSF 18 1.0 prior studies have shown that IL-6 can concentrate in the CSF compartment (e.g e.g during active CNS systemic lupus erythematosus ( 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288463 9562310 408325 10463 6018 IL6 IL-6 IL-6 0 1.3 IL-6 along with TNF- has been reported to be highly expressed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288464 9562310 408325 22551 11892 TNF TNF TNF- 3 0.0 IL-6 along with TNF- has been reported to be highly expressed in perivascular inflammatory 1 JUMiner_v2.2 1 1 tnf; 0 0 0 0 0 0 0 0 288465 9562310 408326 10463 6018 IL6 IL-6 IL-6 14 1.3 expression we did not find a statistically significant elevation of IL-6 in MS CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288466 9562310 408326 11629 6493 LAMC2 CSF CSF 17 1.0 not find a statistically significant elevation of IL-6 in MS CSF 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288467 9562310 408327 10463 6018 IL6 IL-6 IL-6 9 1.3 Moreover we were unable to document an increase in IL-6 during active disease both within a group of MS patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288468 9562310 408330 10463 6018 IL6 IL-6 IL-6 34 1.3 et al. 1990 and Maimone et al. 1991 to correlate IL-6 and CSF parameters of immune mediated disease including percentage IgG 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288469 9562310 408330 11629 6493 LAMC2 CSF CSF 36 1.0 1990 and Maimone et al. 1991 to correlate IL-6 and CSF parameters of immune mediated disease including percentage IgG and elevated 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288470 9562310 408331 10463 6018 IL6 IL-6 IL-6 12 1.3 in the MS and HAM patients suggests either (I) I IL-6 does not play a major role in these disease or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288471 9562310 408331 10463 6018 IL6 IL-6 IL-6 26 1.3 major role in these disease or (II) II detection of IL-6 is unreliable in the CSF of immune-mediated CNS parenchymal disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288472 9562310 408331 11629 6493 LAMC2 CSF CSF 31 1.0 or (II) II detection of IL-6 is unreliable in the CSF of immune-mediated CNS parenchymal disease (because because of instability or 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288473 9562310 408331 10463 6018 IL6 IL-6 IL-6 42 1.3 immune-mediated CNS parenchymal disease (because because of instability or because IL-6 from brain in these disease does not enter the CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288474 9562310 408331 11629 6493 LAMC2 CSF CSF 52 1.0 IL-6 from brain in these disease does not enter the CSF compartment 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288475 9562310 408332 10463 6018 IL6 IL-6 IL-6 5 1.3 It is possible that the IL-6 elevation in ALS is of non-immune origin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288476 9562310 408332 9947 5468 IGFALS ALS ALS 8 0.3 It is possible that the IL-6 elevation in ALS is of non-immune origin 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288477 9562310 408333 10463 6018 IL6 IL-6 IL-6 0 1.3 IL-6 has been shown to induce neuronal differentiation ( Satoh et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288478 9562310 408334 10463 6018 IL6 IL-6 IL-6 1 1.3 Moreover IL-6 has been shown to increase in brain in response to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288479 9562310 408335 10463 6018 IL6 IL-6 IL-6 3 1.3 We speculate that IL-6 may be produced by astrocytes or microglial cells in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288480 9562310 408335 9947 5468 IGFALS ALS ALS 13 0.3 IL-6 may be produced by astrocytes or microglial cells in ALS as a non-specific response to degeneration of motor neurons or 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288481 9562310 408336 10463 6018 IL6 IL-6 IL-6 10 1.3 This non-specific effect may explain the slightly higher levels of IL-6 in OND controls compared to non-neurological disease controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288482 9562310 408337 9947 5468 IGFALS ALS ALS 7 0.3 Future studies of multiple cytokine expression in ALS and other neurological disease would be helpful to distinguish an 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288483 9562310 408337 10463 6018 IL6 IL-6 IL-6 24 1.3 helpful to distinguish an immune versus a non-immune origin of IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288484 9562310 408339 11629 6493 LAMC2 CSF CSF 0 1.0 CSF IL-6 levels in ALS MS (including including relapsing remitting and 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288485 9562310 408339 10463 6018 IL6 IL-6 IL-6 1 1.3 CSF IL-6 levels in ALS MS (including including relapsing remitting and stable 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288486 9562310 408339 9947 5468 IGFALS ALS ALS 4 0.3 CSF IL-6 levels in ALS MS (including including relapsing remitting and stable disease HAM OND 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288487 9562310 408340 11629 6493 LAMC2 CSF CSF 1 1.0 Eleven CSF samples were from patients previously reported ( Ohbo et al. 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288488 9562310 408341 9947 5468 IGFALS ALS ALS 6 0.3 Statistical test results include the following ALS vs OND P =0.0075 ALS vs control P _amp_#x3c 0.001 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288489 9562310 408341 9947 5468 IGFALS ALS ALS 11 0.3 test results include the following ALS vs OND P =0.0075 ALS vs control P _amp_#x3c 0.001 MS vs OND and MS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000688289727488252<>ScoreDetail__5468|IGFALS|0.000688289727488252__11179|SOD1|0.000572368485874859__ 0 0 0 0 0 288490 9562310 408343 11629 6493 LAMC2 CSF CSF 0 1.0 CSF IL-6 levels in MS patients with either relapsing or remitting/stable 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288491 9562310 408343 10463 6018 IL6 IL-6 IL-6 1 1.3 CSF IL-6 levels in MS patients with either relapsing or remitting/stable remitting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288492 9562310 408346 11629 6493 LAMC2 CSF CSF 0 1.0 CSF parameters in an MS patient followed for 15 months with 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288493 9562310 408348 11629 6493 LAMC2 CSF CSF 0 1.0 CSF IL-6 levels in MS or HAM patients that either have 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 288494 9562310 408348 10463 6018 IL6 IL-6 IL-6 1 1.3 CSF IL-6 levels in MS or HAM patients that either have (OCB+) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 288495 9562310 408348 11629 6493 LAMC2 CSF CSF 21 1.0 or do not have (OCB_amp_#x2212;) OCB_amp_#x2212 oligoclonal bands in the CSF 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 282619 9762518 398341 926 620 APP amyloid amyloid 2 2.3 Accumulations of amyloid and extracellular tangles apparently act as irritants causing the activation 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 282620 9762518 398357 2161 1323 C4A C4A C4a 12 1.1 cleaves multiple molecules of both C4 and C2 to generate C4a C4b C2a and C2b 2 JUMiner_v2.2 1 0 0 2 1323 TotalCon:2<>1323|C4A|720|Complete__1324|C4B|721|Complete__<>AvaiableGeneRif=2<>BEST:1323|C4A|0.000529218526542345<>ScoreDetail__1324|C4B|0.000521468863688228__1323|C4A|0.000529218526542345__ 0 0 0 0 0 282621 9762518 398357 2161 1323 C4A C4B C4b 13 1.1 multiple molecules of both C4 and C2 to generate C4a C4b C2a and C2b 2 JUMiner_v2.2 1 0 0 2 1323 TotalCon:2<>1324|C4B|721|Complete__1323|C4A|720|Complete__<>AvaiableGeneRif=2<>BEST:1323|C4A|0.0005433782195602<>ScoreDetail__1324|C4B|0.00048940748689727__1323|C4A|0.0005433782195602__ 0 0 0 0 0 282622 9762518 398358 2161 1323 C4A C4B C4b 1 1.1 The C4b and C2a fragments combine to form the C3 convertase which 2 JUMiner_v2.2 1 0 0 2 1323 TotalCon:2<>1324|C4B|721|Complete__1323|C4A|720|Complete__<>AvaiableGeneRif=2<>BEST:1323|C4A|0.0005433782195602<>ScoreDetail__1324|C4B|0.00048940748689727__1323|C4A|0.0005433782195602__ 0 0 0 0 0 282623 9762518 398359 2161 1323 C4A C4B C4b 3 1.1 Both C3b and C4b have thiol groups exposed that can form covalent bonds with 2 JUMiner_v2.2 1 0 0 2 1323 TotalCon:2<>1324|C4B|721|Complete__1323|C4A|720|Complete__<>AvaiableGeneRif=2<>BEST:1323|C4A|0.0005433782195602<>ScoreDetail__1324|C4B|0.00048940748689727__1323|C4A|0.0005433782195602__ 0 0 0 0 0 282624 9762518 398362 2200 1338 C5AR1 C5A C5a 15 0.3 C3 convertase yields the C5 convertase which cleaves C5 into C5a and C5b the latter combining with C6 C7 C8 and 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 282625 9762518 398365 2161 1323 C4A C4A C4a 4 1.1 The small diffusible fragments C4a C3a and C5a produced by complement activation are called anaphylatoxins 2 JUMiner_v2.2 1 0 0 2 1323 TotalCon:2<>1323|C4A|720|Complete__1324|C4B|721|Complete__<>AvaiableGeneRif=2<>BEST:1323|C4A|0.000529218526542345<>ScoreDetail__1324|C4B|0.000521468863688228__1323|C4A|0.000529218526542345__ 0 0 0 0 0 282626 9762518 398365 2200 1338 C5AR1 C5A C5a 7 0.3 The small diffusible fragments C4a C3a and C5a produced by complement activation are called anaphylatoxins because of their 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 282627 9762518 398369 926 620 APP amyloid amyloid 30 2.3 chromogranin A ( Taupenot et al . 1996 and _amp_#x3b2 -amyloid protein ( Klegeris et al . 1994 as well as 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 282628 9762518 398377 926 620 APP amyloid amyloid 13 2.3 activators of complement have for example been found in AD amyloid deposits 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 282629 9762518 398378 926 620 APP amyloid amyloid 4 2.3 The most prominent is _amp_#x3b2 -amyloid protein 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 282630 9762518 398379 926 620 APP amyloid amyloid 2 2.3 Others are amyloid P C-reactive protein and the Hageman factor ( McGeer and 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 282631 9762518 398384 926 620 APP amyloid amyloid 9 2.3 Subsequent immunohistochemical and other studies have revealed that the amyloid deposits in AD are also associated with many other extracellular 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 282632 9762518 398387 11629 6493 LAMC2 CSF CSF 34 0.0 cytokines and their receptors in brain tissue and/or and or CSF (for for review see McGeer and McGeer 1997b 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 282639 9769023 398468 20996 11179 SOD1 ALS ALS 31 0.0 AD Parkinson's disease (PD), PD and amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000692485252628879<>ScoreDetail__5468|IGFALS|0.000190415741034592__11179|SOD1|0.000692485252628879__ 0 0 0 0 0 282640 9769023 398473 926 620 APP amyloid amyloid 2 1.0 Accumulations of amyloid extracellular tangles or Lewy bodies apparently act as irritants causing 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 284043 9850924 401204 926 620 APP amyloid amyloid 2 1.0 Accumulations of amyloid and extracellular tangles apparently act as irritants causing the activation 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 276178 10225668 387926 11629 6493 LAMC2 CSF CSF 5 0.0 We determined the cerebrospinal fluid (CSF) CSF levels of adenosine a mediator of cerebral blood flow regulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 276179 10225668 387927 20996 11179 SOD1 ALS ALS 27 0.0 acute meningitis (n=10, n=10 p_lt_0.0001 or amyotrophic lateral sclerosis (ALS, ALS n=12 p_lt_0.05 (Mann-Whitney Mann-Whitney U-test 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000888270961263662<>ScoreDetail__5468|IGFALS|0.000888270961263662__11179|SOD1|0.000716504435406718__ 0 0 0 0 0 276180 10225668 387928 22104 11785 THBS1 TSP TSP 19 0.0 virus type I-associated myelopathy/tropical myelopathy tropical spastic paraparesis (HAM/TSP, HAM TSP p_lt_0.0001 acute meningitis (p_lt_0.0001), p_lt_0.0001 ALS (p_lt_0.05) p_lt_0.05 (Mann-Whitney Mann-Whitney 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 276181 10225668 387928 20996 11179 SOD1 ALS ALS 24 0.0 spastic paraparesis (HAM/TSP, HAM TSP p_lt_0.0001 acute meningitis (p_lt_0.0001), p_lt_0.0001 ALS (p_lt_0.05) p_lt_0.05 (Mann-Whitney Mann-Whitney U-test or acute-stage cerebral infarction (p_lt_0.005, 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000888270961263662<>ScoreDetail__5468|IGFALS|0.000888270961263662__11179|SOD1|0.000716504435406718__ 0 0 0 0 0 276182 10225668 387929 22104 11785 THBS1 TSP TSP 5 0.0 In the analysis of 41 HAM/TSP HAM TSP patients the neopterin levels were significantly correlated with the cell 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 276183 10225668 387929 11629 6493 LAMC2 CSF CSF 22 0.0 correlated with the cell number and glucose levels in the CSF and were a sensitive marker of inflammation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 276184 10225668 387930 22104 11785 THBS1 TSP TSP 3 0.0 Several of the HAM/TSP HAM TSP patients with increased adenosine levels were probably complicated with other 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 276185 10225668 387931 22104 11785 THBS1 TSP TSP 6 0.0 The increased neopterin levels in the HAM/TSP HAM TSP group persisted suggesting that the mononuclear cellular infiltration remained for 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 273829 10417811 383077 926 620 APP amyloid amyloid 49 1.3 amyotrophic lateral sclerosis and (5) 5 transgenic mice overexpressing mutant amyloid precursor protein which exhibits age-related amyloid deposition characteristic of Alzheimer's 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 273830 10417811 383077 926 620 APP amyloid amyloid 55 1.3 transgenic mice overexpressing mutant amyloid precursor protein which exhibits age-related amyloid deposition characteristic of Alzheimer's disease 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 275659 10525172 386981 20996 11179 SOD1 ALS ALS 29 1.4 (PD), PD multiple sclerosis (MS), MS amyotrophic lateral sclerosis (ALS) ALS and the parkinsonism dementia complex of Guam 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000775018816394618<>ScoreDetail__5468|IGFALS|0.000377891366176734__11179|SOD1|0.000775018816394618__ 0 0 0 0 0 275660 10525172 386984 926 620 APP amyloid amyloid 15 1.0 generated by microglial cells activated by pro-inflammatory cytokines or _amp_#x3b2 -amyloid peptide (_amp_#x3b2;-A) _amp_#x3b2 -A and by neurons in three different 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 275661 10525172 386988 20996 11179 SOD1 ALS ALS 35 1.4 (PD), PD multiple sclerosis (MS), MS amyotrophic lateral sclerosis (ALS) ALS and the parkinsonism dementia complex of Guam is consistent with 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000775018816394618<>ScoreDetail__5468|IGFALS|0.000377891366176734__11179|SOD1|0.000775018816394618__ 0 0 0 0 0 275662 10525172 387001 20996 11179 SOD1 SOD SOD 13 1.4 with O 2 _amp_#x2212 three-fold faster than superoxide dismutase (SOD) SOD ( k =2.3_amp_#xd7 10 9 M _amp_#x2212 1 s _amp_#x2212 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275663 10525172 387001 20996 11179 SOD1 SOD SOD 33 1.4 NO is the only known biomolecule capable of out competing SOD for available O 2 _amp_#x2212 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275664 10525172 387011 20996 11179 SOD1 SOD SOD 4 1.4 Because the concentrations of SOD and O 2 _amp_#x2212 in a given tissue are relatively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275665 10525172 387012 14533 7872 NOS1 NOS NOS 8 3.0 In the CNS three NO-synthase isoforms neuronal Type-I NOS inducible Type-II NOS and endothelial Type-III NOS can generate NO 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275666 10525172 387012 14533 7872 NOS1 NOS NOS 11 3.0 the CNS three NO-synthase isoforms neuronal Type-I NOS inducible Type-II NOS and endothelial Type-III NOS can generate NO 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275667 10525172 387012 14533 7872 NOS1 NOS NOS 15 3.0 isoforms neuronal Type-I NOS inducible Type-II NOS and endothelial Type-III NOS can generate NO 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275668 10525172 387014 14533 7872 NOS1 NOS NOSs 16 1.2 great deal of detail about the biochemistry and pharmacology of NOSs as there are many excellent review articles 53 78 80 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275669 10525172 387016 14533 7872 NOS1 NOS NOS 1 3.0 Type-I NOS has been detected in the cerebellum the hypothalamus the striatum 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275670 10525172 387017 14533 7872 NOS1 NOS NOS 1 3.0 Type-II NOS is located predominantly in microglia and astrocytes 43 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275671 10525172 387018 14533 7872 NOS1 NOS NOS 1 3.0 Type-III NOS has been detected in microvessels and motor neurons from rodents 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275672 10525172 387022 14533 7872 NOS1 NOS NOS 6 3.0 By reaction of NO from Type-I NOS with O 2 _amp_#x2212 from the mitochondrial respiratory chain 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275673 10525172 387023 20996 11179 SOD1 SOD SOD 20 1.4 be unlikely since Okabe et al 65 recently shown that SOD the enzyme which scavengers O 2 _amp_#x2212 colocalizes with NOS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275674 10525172 387023 14533 7872 NOS1 NOS NOS 31 3.0 SOD the enzyme which scavengers O 2 _amp_#x2212 colocalizes with NOS in the hippocampus and the cerebellum where NO plays an 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275675 10525172 387024 20996 11179 SOD1 ALS ALS 20 1.4 neurotransmission 61 and mitochondrial dysfunction including focal trauma epileptic seizure ALS PD and other neurodegenerative diseases the excessive intracellular calcium accumulation 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000775018816394618<>ScoreDetail__5468|IGFALS|0.000377891366176734__11179|SOD1|0.000775018816394618__ 0 0 0 0 0 275676 10525172 387024 14533 7872 NOS1 NOS NOS 44 3.0 abnormal activation of Ca 2 -dependent enzymes including the Type-I NOS 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275677 10525172 387036 10437 5992 IL1B IL-1 IL-1 8 1.0 Microglial cells can be activated by pro-inflammatory cytokines IL-1 IL-6 and TNF_amp_#x3b1 as well as by _amp_#x3b2 -amyloid peptide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275678 10525172 387036 10463 6018 IL6 IL-6 IL-6 9 1.0 Microglial cells can be activated by pro-inflammatory cytokines IL-1 IL-6 and TNF_amp_#x3b1 as well as by _amp_#x3b2 -amyloid peptide (_amp_#x3b2;-A) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275679 10525172 387036 926 620 APP amyloid amyloid 16 1.0 cytokines IL-1 IL-6 and TNF_amp_#x3b1 as well as by _amp_#x3b2 -amyloid peptide (_amp_#x3b2;-A) _amp_#x3b2 -A 82 90 the first 42 amino 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 275680 10525172 387036 926 620 APP amyloid amyloid 30 1.0 _amp_#x3b2 -A 82 90 the first 42 amino acids of amyloid precursor protein (APP) APP ( Fig 6 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 275681 10525172 387036 926 620 APP APP APP 33 0.3 the first 42 amino acids of amyloid precursor protein (APP) APP ( Fig 6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275682 10525172 387039 926 620 APP amyloid amyloid 32 1.0 and thus peroxynitrite the soluble _amp_#x3b2 -A monomer a diffuse amyloid deposit and mature filamentous amyloid plaques 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 275683 10525172 387039 926 620 APP amyloid amyloid 37 1.0 _amp_#x3b2 -A monomer a diffuse amyloid deposit and mature filamentous amyloid plaques 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 275684 10525172 387047 14533 7872 NOS1 NOS NOS 36 3.0 on microglia cultures Walker et al 89 by measuring Type-I NOS gene expression on human microglia cultures and Vodovotz et al 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275685 10525172 387054 14533 7872 NOS1 NOS NOS 15 3.0 the blood_amp_#x2013 brain barrier associated with enhanced expression of Type-III NOS in microvessels and the presence of numerous inducible Type-II NOS 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275686 10525172 387054 14533 7872 NOS1 NOS NOS 25 3.0 NOS in microvessels and the presence of numerous inducible Type-II NOS immunoreactive microglia 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275687 10525172 387056 926 620 APP amyloid amyloid 11 1.0 a pathway for peroxynitrite formation may be postulated in cerebral amyloid angiopathy which is frequently associated with AD 84 93 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 275688 10525172 387058 14533 7872 NOS1 NOS NOS 2 3.0 By Type-I NOS activity in arginine- or tetrahydrobiopterin-depleted conditions 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275689 10525172 387059 14533 7872 NOS1 NOS NOS 1 3.0 Type-I NOS and Type-II NOS catalyze electron transfer from NADPH to O 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275690 10525172 387059 14533 7872 NOS1 NOS NOS 4 3.0 Type-I NOS and Type-II NOS catalyze electron transfer from NADPH to O 2 in the 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275691 10525172 387060 14533 7872 NOS1 NOS NOS 11 3.0 At low arginine concentrations 62 67 however Type-II NOS strongly reduces the NADPH oxidation rate while Type-I NOS still 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275692 10525172 387060 14533 7872 NOS1 NOS NOS 20 3.0 Type-II NOS strongly reduces the NADPH oxidation rate while Type-I NOS still oxidizes NADPH with an unmodified rate and then reduces 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275693 10525172 387062 14533 7872 NOS1 NOS NOS-transfected 13 1.2 a 20-fold increase of O 2 _amp_#x2212 formation in Type-I NOS-transfected human kidney 293 cells as the cytosolic -arginine levels decreased 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275694 10525172 387063 14533 7872 NOS1 NOS NOS 1 3.0 The NOS inhibitor N -nitro--arginine methyl ester virtually abolished the O 2 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275695 10525172 387064 14533 7872 NOS1 NOS NOS 6 3.0 Therefore at low arginine concentrations Type-I NOS produces simultaneously O 2 _amp_#x2212 and NO at the same 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275696 10525172 387065 14533 7872 NOS1 NOS NOS 17 3.0 by Gorren and Mayer 32 in a study of Type-I NOS activity as a function of tetrahydrobiopterin (BH BH 4 concentration 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275697 10525172 387066 14533 7872 NOS1 NOS NOS 1 3.0 Type-I NOS is a dimeric enzyme which exhibits strong anti-cooperative binding of 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275698 10525172 387068 14533 7872 NOS1 NOS NOS 15 3.0 10 _amp_#x2212 9 M no BH 4 molecule binds Type-I NOS and O 2 _amp_#x2212 is produced whereas at high BH 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275699 10525172 387073 20996 11179 SOD1 ALS ALS 14 1.4 suggested to contribute to tissue damage in AD PD MS ALS and the parkinsonism dementia complex of Guam 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000775018816394618<>ScoreDetail__5468|IGFALS|0.000377891366176734__11179|SOD1|0.000775018816394618__ 0 0 0 0 0 275700 10525172 387076 20996 11179 SOD1 SOD SOD 15 1.4 1993 Beckman et al 8 pointed out that mutations in SOD associated with the autosomal dominant inheritance of familial ALS could 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275701 10525172 387076 20996 11179 SOD1 ALS ALS 24 1.4 in SOD associated with the autosomal dominant inheritance of familial ALS could both double the steady state concentration of O 2 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000775018816394618<>ScoreDetail__5468|IGFALS|0.000377891366176734__11179|SOD1|0.000775018816394618__ 0 0 0 0 0 275702 10525172 387076 20996 11179 SOD1 SOD SOD 38 1.4 the steady state concentration of O 2 _amp_#x2212 by decreasing SOD activity by 50% and increase nitration of critical cellular targets 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275703 10525172 387076 20996 11179 SOD1 SOD SOD 65 1.4 peroxynitrite to copper a strong tyrosyl nitration catalysis in the SOD active site 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275704 10525172 387078 20996 11179 SOD1 ALS ALS-associated 18 1.4 strengthened by the demonstration that the zinc affinity of four ALS-associated SOD mutants was decreased up to 30-fold compared with wild-type 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000775018816394618<>ScoreDetail__5468|IGFALS|0.000377891366176734__11179|SOD1|0.000775018816394618__ 0 0 0 0 0 275705 10525172 387078 20996 11179 SOD1 SOD SOD 19 1.4 by the demonstration that the zinc affinity of four ALS-associated SOD mutants was decreased up to 30-fold compared with wild-type SOD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275706 10525172 387078 20996 11179 SOD1 SOD SOD 29 1.4 SOD mutants was decreased up to 30-fold compared with wild-type SOD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275707 10525172 387079 14282 7739 NEFL NF-L NF-L 9 1.3 These investigators also showed that the motor neuron protein neurofilament- NF-L could bind zinc atoms with sufficient affinity to potentially remove 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275708 10525172 387079 20996 11179 SOD1 SOD SOD 23 1.4 zinc atoms with sufficient affinity to potentially remove zinc from SOD and that the loss of zinc from wild-type SOD almost 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275709 10525172 387079 20996 11179 SOD1 SOD SOD 32 1.4 from SOD and that the loss of zinc from wild-type SOD almost doubled the efficiency of this enzyme for catalyzing for 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275710 10525172 387080 20996 11179 SOD1 ALS ALS 26 1.4 al 13 14 detected more nitration in motor neurons of ALS than in controls 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000775018816394618<>ScoreDetail__5468|IGFALS|0.000377891366176734__11179|SOD1|0.000775018816394618__ 0 0 0 0 0 275711 10525172 387081 20996 11179 SOD1 ALS ALS 19 1.4 tyrosine residues in motor neurons of the spinal cord in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000775018816394618<>ScoreDetail__5468|IGFALS|0.000377891366176734__11179|SOD1|0.000775018816394618__ 0 0 0 0 0 275712 10525172 387082 14282 7739 NEFL NF-L NF-L 22 1.3 no significant qualitative or quantitative modifications in the nitrotyrosine-immunoreactivity of NF-L isolated from sporadic ALS cervical spinal cord tissue as compared 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275713 10525172 387082 20996 11179 SOD1 ALS ALS 26 1.4 quantitative modifications in the nitrotyrosine-immunoreactivity of NF-L isolated from sporadic ALS cervical spinal cord tissue as compared with age-matched non-ALS controls 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000775018816394618<>ScoreDetail__5468|IGFALS|0.000377891366176734__11179|SOD1|0.000775018816394618__ 0 0 0 0 0 275714 10525172 387087 14533 7872 NOS1 NOS NOS 23 3.0 of mice with EAE by Lin et al 51 Type-II NOS mRNA has been detected in EAE models by Cross et 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275715 10525172 387089 22551 11892 TNF TNF TNF 20 0.3 an overexpression of the proinflammatory cytokines IL1-_amp_#x3b2 IL2 IFN_amp_#x3b3 and TNF and a defective production of the anti-inflammatory cytokine TGF-_amp_#x3b2 associated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275716 10525172 387089 14533 7872 NOS1 NOS NOS 36 3.0 the anti-inflammatory cytokine TGF-_amp_#x3b2 associated with an increase in Type-II NOS mRNA expression and nitrite production in peripheral blood mononuclear cells 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275717 10525172 387089 10436 5991 IL1A IL1 IL1-_amp_#x3b2 16 0.0 et al 71 reported an overexpression of the proinflammatory cytokines IL1-_amp_#x3b2 IL2 IFN_amp_#x3b3 and TNF and a defective production of the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275718 10525172 387089 10452 6001 IL2 IL2 IL2 17 0.0 al 71 reported an overexpression of the proinflammatory cytokines IL1-_amp_#x3b2 IL2 IFN_amp_#x3b3 and TNF and a defective production of the anti-inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275719 10525172 387102 6054 2983 DNTT TDT TdT 31 0.0 strand breaking (detected detected by the deoxynucleotidyl transferase histochemical technique TdT and tyrosine-nitrated proteins (detected detected by immunocytochemistry using antibodies direct 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275720 10525172 387103 6054 2983 DNTT TDT TdT-labeled 6 0.0 They demonstrated that the majority of TdT-labeled nuclei are associated with neurons exhibiting an up-regulation of nitrotyrosine 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275721 10525172 387116 14533 7872 NOS1 NOS NOS 10 3.0 Beal 7 reported the protective effect of Type-I NOS inhibitors on the neurotoxicity of MPTP in both mice and 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275722 10525172 387123 20996 11179 SOD1 ALS ALS 22 1.4 brain of patients with neurodegenerative disorders such as AD PD ALS and MS has led Mc Geer and Mc Geer 56 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000775018816394618<>ScoreDetail__5468|IGFALS|0.000377891366176734__11179|SOD1|0.000775018816394618__ 0 0 0 0 0 275723 10525172 387126 14533 7872 NOS1 NOS NOS 8 3.0 Under normal conditions neurons produce NO via Type-I NOS as an intracellular messenger which has an important role in 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275724 10525172 387129 14533 7872 NOS1 NOS NOS 12 3.0 contrary under either -arginine- or BH 4 -depleted conditions Type-I NOS monomers can function independently of each other 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275725 10525172 387131 14533 7872 NOS1 NOS NOS 21 3.0 second step of the neurodegenerative process by induction of Type-II NOS which produces large amounts of NO and stimulation of NADPH-oxidase 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275726 10525172 387134 14533 7872 NOS1 NOS NOS 1 3.0 Type-III NOS expressed in microvessels and motor neurons can also generate NO 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275727 10525172 387136 14533 7872 NOS1 NOS NOS 7 3.0 These authors observed an expression of Type-III NOS but not of Type-I NOS by motor neurons cultured with 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275728 10525172 387136 14533 7872 NOS1 NOS NOS 12 3.0 observed an expression of Type-III NOS but not of Type-I NOS by motor neurons cultured with brain-derived neurotrophic factor (BDNF) BDNF 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275729 10525172 387136 1624 1033 BDNF BDNF BDNF 21 1.9 NOS by motor neurons cultured with brain-derived neurotrophic factor (BDNF) BDNF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275730 10525172 387138 14533 7872 NOS1 NOS NOS 8 3.0 On the contrary trophic factor deprivation promoted Type-I NOS expression and cell death by apoptosis 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275731 10525172 387139 14533 7872 NOS1 NOS NOS 11 3.0 motor neuron degeneration was promoted by NO produced by Type-I NOS and reversed by SOD suggesting that formation of peroxynitrite initiates 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275732 10525172 387139 20996 11179 SOD1 SOD SOD 15 1.4 promoted by NO produced by Type-I NOS and reversed by SOD suggesting that formation of peroxynitrite initiates apoptosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 275733 10525172 387142 14533 7872 NOS1 NOS NOS 28 3.0 mechanism we described previously for generation of peroxynitrite by Type-I NOS under -arginine- or BH 4 -depleted conditions 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275734 10525172 387149 14533 7872 NOS1 NOS NOS-catalyzed 3 1.2 Schematic representation of NOS-catalyzed reactions 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000675259191799155<>ScoreDetail__7873|NOS2A|0.00066509810098544__7872|NOS1|0.000675259191799155__ 0 0 0 0 0 275735 10525172 387158 17461 9508 PSEN1 FAD FAD 28 0.3 substrates -arginine NADPH and O 2 and require five cofactors FAD FMN calmodulin (CaM), CaM tetrahydrobiopterin (BH BH 4 and heme 1 JUMiner_v2.2 1 2 nadph 0 2 3585 TotalCon:3<>1101|BRCA2|675|Complete__3585|FANCD2|2177|Complete__9508|PSEN1|5663|Complete__<>AvaiableGeneRif=3<>BEST:3585|FANCD2|0.000565392205550834<>ScoreDetail__1101|BRCA2|0.000324533567436429__9508|PSEN1|0.000517984626120048__3585|FANCD2|0.000565392205550834__ 0 0 0 0 0 275736 10525172 387158 7638 3768 FMN1 FMN FMN 29 0.2 -arginine NADPH and O 2 and require five cofactors FAD FMN calmodulin (CaM), CaM tetrahydrobiopterin (BH BH 4 and heme 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252893 11173059 346404 8792 4574 GRIA4 GLUR4 GluR4 19 1.6 central nervous system and are made of four subunits GluR1_amp_#x2013 GluR4 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252894 11173059 346405 8790 4572 GRIA2 GLUR2 GluR2 4 1.9 The presence of the GluR2 subunit makes the AMPA receptor impermeable to Ca 2 preventing 14 JUMiner_v2.2 1 0 0 2 4572 TotalCon:2<>4572|GRIA2|2891|Complete__4594|GRM2|2912|Complete__<>AvaiableGeneRif=2<>BEST:4572|GRIA2|0.000724379713432762<>ScoreDetail__4594|GRM2|0.000620688682306141__4572|GRIA2|0.000724379713432762__ 0 0 0 0 0 252895 11173059 346406 8790 4572 GRIA2 GLUR2 GluR2 23 1.9 display low levels of mRNA and protein synthesis for the GluR2 AMPA receptor subunit ( Williams et al. 1997 14 JUMiner_v2.2 1 0 0 2 4572 TotalCon:2<>4572|GRIA2|2891|Complete__4594|GRM2|2912|Complete__<>AvaiableGeneRif=2<>BEST:4572|GRIA2|0.000724379713432762<>ScoreDetail__4594|GRM2|0.000620688682306141__4572|GRIA2|0.000724379713432762__ 0 0 0 0 0 252896 11173059 346447 20018 10941 SLC1A3 EAAT1 EAAT-1 10 0.3 Five human transporters have already been cloned the glial transporters EAAT-1 and EAAT-2 and the neuronal transporters EAAT-3 EAAT-4 and EAAT-5 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252897 11173059 346447 20017 10940 SLC1A2 EAAT2 EAAT-2 12 0.3 transporters have already been cloned the glial transporters EAAT-1 and EAAT-2 and the neuronal transporters EAAT-3 EAAT-4 and EAAT-5 (the the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252898 11173059 346447 20016 10939 SLC1A1 EAAT3 EAAT-3 17 0.3 the glial transporters EAAT-1 and EAAT-2 and the neuronal transporters EAAT-3 EAAT-4 and EAAT-5 (the the latter two also function as 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252899 11173059 346447 20021 10944 SLC1A6 EAAT4 EAAT-4 18 0.3 glial transporters EAAT-1 and EAAT-2 and the neuronal transporters EAAT-3 EAAT-4 and EAAT-5 (the the latter two also function as glutamate-gated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252900 11173059 346447 20022 10945 SLC1A7 EAAT5 EAAT-5 20 0.3 EAAT-1 and EAAT-2 and the neuronal transporters EAAT-3 EAAT-4 and EAAT-5 (the the latter two also function as glutamate-gated chloride channels 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252901 11173059 346455 20017 10940 SLC1A2 EAAT2 EAAT-2 12 0.3 originates from a decreased expression of the glial glutamate transporter EAAT-2 ( Rothstein et al. 1995 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252902 11173059 346456 20017 10940 SLC1A2 EAAT2 EAAT-2 3 0.3 The loss of EAAT-2 is not related to genomic mutations and selective EAAT 2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252903 11173059 346458 20017 10940 SLC1A2 EAAT2 EAAT-2 1 0.3 Alternatively EAAT-2 deficiency could derive from defective translational or post-translational mechanisms secondary 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252904 11173059 346466 8790 4572 GRIA2 GLUR2 GluR2 1 1.9 The GluR2 subunit of the AMPA glutamate receptor and/or and or the 14 JUMiner_v2.2 1 0 0 2 4572 TotalCon:2<>4572|GRIA2|2891|Complete__4594|GRM2|2912|Complete__<>AvaiableGeneRif=2<>BEST:4572|GRIA2|0.000724379713432762<>ScoreDetail__4594|GRM2|0.000620688682306141__4572|GRIA2|0.000724379713432762__ 0 0 0 0 0 252905 11173059 346482 1624 1033 BDNF BDNF BDNF 7 1.9 Neurotrophic factors such as brain-derived neurotrophic factor (BDNF), BDNF ciliary neurotrophic factor (CNTF), CNTF and insulin-like growth factor-1 (IGF-1) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252906 11173059 346482 4649 2169 CNTF CNTF CNTF 11 2.9 as brain-derived neurotrophic factor (BDNF), BDNF ciliary neurotrophic factor (CNTF), CNTF and insulin-like growth factor-1 (IGF-1) IGF-1 enhance motor neuron survival 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252907 11173059 346482 9939 5464 IGF1 IGF1 IGF-1 16 1.2 ciliary neurotrophic factor (CNTF), CNTF and insulin-like growth factor-1 (IGF-1) IGF-1 enhance motor neuron survival in vitro and can also exert 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252908 11173059 346489 4649 2169 CNTF CNTF CNTF 4 2.9 A mutation of the CNTF gene occurs in 2_amp_#x2013 3% of the human population leading 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252909 11173059 346490 4649 2169 CNTF CNTF CNTF 5 2.9 However the mutation of the CNTF gene may be deleterious when associated with mutations of other 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252910 11173059 346490 11824 6596 LIF LIF LIF 23 1.7 of other relevant genes such as leukemia inhibitory factor (LIF) LIF ( Sendtner et al. 1996 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252911 11173059 346491 11824 6596 LIF LIF LIF 0 1.7 LIF is another neurotrophic factor for motor neurons and a mutation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252912 11173059 346491 11824 6596 LIF LIF LIF 13 1.7 neurotrophic factor for motor neurons and a mutation of the LIF gene has been detected in a small minority of amyotrophic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252913 11173059 346496 1576 990 BCL2 Bcl-2 Bcl-2 18 1.0 biochemical marker of apoptosis the altered expression of mRNA for Bcl-2 and Bax (an an anti-apoptotic and a proapoptotic gene respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252914 11173059 346498 1576 990 BCL2 Bcl-2 Bcl-2 23 1.0 and Bad (proapoptotic) proapoptotic genes is increased whereas that of Bcl-2 and Bcl-xL (anti-apoptotic) anti-apoptotic is decreased ( Vukosavic et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252915 11173059 346499 1576 990 BCL2 Bcl-2 Bcl-2 11 1.0 double transgenic mice expressing human mutant superoxide dismutase and human Bcl-2 the overexpression of Bcl-2 is associated with a significant delay 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252916 11173059 346499 1576 990 BCL2 Bcl-2 Bcl-2 15 1.0 human mutant superoxide dismutase and human Bcl-2 the overexpression of Bcl-2 is associated with a significant delay in disease onset ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252917 11173059 346524 926 620 APP amyloid amyloid 20 17.4 the formation of Lewy bodies and its aggregation in insoluble amyloid fibrils seems to precede the accumulation of ubiquitin and neurofilaments 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252918 11173059 346536 23620 12513 UCHL1 UCHL1 UCH-L1 16 1.3 mutation in exon 4 of the ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) UCH-L1 gene has been detected on chromosome 4 indicating that abnormal 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252919 11173059 346554 13412 7214 MPHOSPH6 MPP MPP 11 0.0 converted by monoamino oxidase-B into the methyl phenylpyridinium ion (MPP MPP which is actively taken up by dopaminergic neurons and concentrated 1 JUMiner_v2.2 1 0 0 2 7225 TotalCon:2<>7214|MPHOSPH6|10200|Complete__7225|MPZ|4359|Complete__<>AvaiableGeneRif=2<>BEST:7225|MPZ|0.00108555412199137<>ScoreDetail__7214|MPHOSPH6|0.000567789078700504__7225|MPZ|0.00108555412199137__ 0 0 0 0 0 252920 11173059 346555 13412 7214 MPHOSPH6 MPP MPP 0 0.0 MPP inhibits mitochondrial complex I reductase resulting in a decrease in 1 JUMiner_v2.2 1 0 0 2 7225 TotalCon:2<>7214|MPHOSPH6|10200|Complete__7225|MPZ|4359|Complete__<>AvaiableGeneRif=2<>BEST:7225|MPZ|0.00108555412199137<>ScoreDetail__7214|MPHOSPH6|0.000567789078700504__7225|MPZ|0.00108555412199137__ 0 0 0 0 0 252921 11173059 346563 13744 7475 MT-TA TRNA tRNA 20 1.0 there to be a significant association between A4336G at the tRNA Glu gene and Parkinson's disease ( Tan et al. 2000 14 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 252922 11173059 346581 20070 11049 SLC6A3 DAT DAT 11 0.3 under scrutiny included those for tyrosine hydroxylase dopamine transporter (DAT), DAT dopamine receptor D2 D3 D4 and D5 monoamino oxidases A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252923 11173059 346582 20070 11049 SLC6A3 DAT DAT 10 0.3 A significant association between Parkinson's disease and specific polymorphisms of DAT dopamine receptor D2 and D4 monoamino oxidase-A monoamino oxidase-B and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252924 11173059 346594 5344 2595 CYP1A1 CYP CYP 6 0.6 The genes of cytochrome P 450 (CYP) CYP enzymes and particularly its CYP2D6 polymorphism are the most extensively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252925 11173059 346594 5359 2625 CYP2D6 CYP2D6 CYP2D6 11 0.6 of cytochrome P 450 (CYP) CYP enzymes and particularly its CYP2D6 polymorphism are the most extensively investigated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252926 11173059 346595 5359 2625 CYP2D6 CYP2D6 CYP2D6 13 0.6 showed a significant association of the poor metabolizer genotype of CYP2D6 with an increased risk of Parkinson's disease but opposite results 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252927 11173059 346598 8879 4641 GSTT1 GSTT1 GSTT1 17 0.3 of exogenous toxins and the frequency of deletions of its GSTT1 locus is higher in Parkinson's disease patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252928 11173059 346600 8877 4638 GSTP1 GSTP1 GSTP1 7 0.3 In one study the genotype distribution of GSTP1 (another another locus of glutathione transferase significantly differed between patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252929 11173059 346605 8240 4232 GDNF GDNF GDNF 19 1.7 neurons in vivo including glial cell line-derived neurotrophic factor (GDNF), GDNF basic fibroblast growth factor (bFGF), bFGF brain-derived neurotrophic factor neurotrophin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252930 11173059 346605 14766 8053 NUDT6 bFGF bFGF 24 1.0 line-derived neurotrophic factor (GDNF), GDNF basic fibroblast growth factor (bFGF), bFGF brain-derived neurotrophic factor neurotrophin 3 neurotrophin 4/5, 4 5 ciliary 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252931 11173059 346606 8240 4232 GDNF GDNF GDNF 7 1.7 Among these the most promising is the GDNF family of proteins and clinical trials with intraventricular administration of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252932 11173059 346606 8240 4232 GDNF GDNF GDNF 18 1.7 family of proteins and clinical trials with intraventricular administration of GDNF are currently underway 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252933 11173059 346607 8240 4232 GDNF GDNF GDNF 8 1.7 A polymorphism in the coding region of the GDNF gene was recently detected but its possible association with Parkinson's 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252934 11173059 346622 1576 990 BCL2 Bcl-2 Bcl-2 8 1.0 The apoptosis-effector molecule caspase-3 and the anti-apoptotic molecule Bcl-2 are overexpressed in the basal ganglia of patients with Parkinson's 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252935 11173059 346625 1576 990 BCL2 Bcl-2 Bcl-2 8 1.0 Gene polymorphisms of apoptosis-related factors (e.g., e.g. Bax and Bcl-2 or apoptosis-effector molecules (e.g., e.g. caspase enzymes have still to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252936 11173059 346632 926 620 APP amyloid amyloid 10 17.4 plaques are spherical multicellular lesions containing extracellular deposits of _amp_#x3b2 -amyloid protein which is mostly in a fibrillar form ( Selkoe 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252937 11173059 346635 12369 6893 MAPT tau tau 10 1.7 They are composed of hyperphosphorylated insoluble forms of microtubule-associated protein tau often conjugated with ubiquitin ( Selkoe 1999 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252938 11173059 346637 926 620 APP amyloid amyloid 3 17.4 Role of the _amp_#x3b2 -amyloid protein 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252939 11173059 346638 926 620 APP amyloid amyloid 9 17.4 It is a widely accepted concept that deposition of _amp_#x3b2 -amyloid protein is the key event in the pathogenesis of Alzheimer 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252940 11173059 346638 926 620 APP amyloid amyloid 28 17.4 Alzheimer disease _amp_#x3b2 -Amyloid protein derives from a precursor named amyloid precursor protein which in neurons consists of 695-amino acid residues 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252941 11173059 346639 926 620 APP amyloid amyloid 1 17.4 The amyloid precursor protein is a transmembrane molecule with a long extracellular 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252942 11173059 346640 926 620 APP amyloid amyloid 7 17.4 Under physiological conditions a small amount of amyloid precursor protein undergoes secretory cleavage of a long extracellular portion 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252943 11173059 346642 926 620 APP amyloid amyloid 6 17.4 In Alzheimer disease the processing of amyloid precursor protein is significantly altered 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252944 11173059 346643 926 620 APP amyloid amyloid 3 17.4 Increased amounts of amyloid precursor protein are cleaved by another endoprotease named _amp_#x3b2 -secretase 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252945 11173059 346644 926 620 APP amyloid amyloid 21 17.4 the putative intramembranous portion leads to the generation of _amp_#x3b2 -amyloid protein molecules of 40 or 42 amino acid residues _amp_#x3b2 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252946 11173059 346651 926 620 APP amyloid amyloid 25 17.4 of disease and are accounted for by mutations of the amyloid precursor protein presenilin-1 (PS-1), PS-1 or presenilin-2 gene (PS-2) PS-2 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252947 11173059 346651 17461 9508 PSEN1 PS1 PS-1 29 4.7 for by mutations of the amyloid precursor protein presenilin-1 (PS-1), PS-1 or presenilin-2 gene (PS-2) PS-2 ( Rosenberg 2000 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252948 11173059 346651 17462 9509 PSEN2 PS2 PS-2 33 3.4 amyloid precursor protein presenilin-1 (PS-1), PS-1 or presenilin-2 gene (PS-2) PS-2 ( Rosenberg 2000 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9509|PSEN2|5664|Complete__20642|TAS2R64P|338412|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252949 11173059 346652 926 620 APP amyloid amyloid 3 17.4 The gene of amyloid precursor protein maps on chromosome 21q21.2 and at least 7 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252950 11173059 346653 926 620 APP amyloid amyloid 22 17.4 _amp_#x3b3 -secretase cleavage sites altering the normal proteolysis of the amyloid precursor protein 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252951 11173059 346654 17461 9508 PSEN1 PS1 PS-1 1 4.7 The PS-1 gene locates on chromosome 14q24.3 and mutations in this gene 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252952 11173059 346655 17461 9508 PSEN1 PS1 PS-1 0 4.7 PS-1 codes for a 467-amino acid protein that is an integral 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252953 11173059 346656 17461 9508 PSEN1 PS1 PS-1 0 4.7 PS-1 function is not entirely known but it may be involved 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252954 11173059 346657 17461 9508 PSEN1 PS1 PS-1 6 4.7 More than 60 mutations of the PS-1 gene have been associated with early-onset familial Alzheimer disease and 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252955 11173059 346658 17462 9509 PSEN2 PS2 PS-2 1 3.4 The PS-2 gene maps on chromosome 1q31-q42 and codes for a 448-amino 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9509|PSEN2|5664|Complete__20642|TAS2R64P|338412|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252956 11173059 346658 17461 9508 PSEN1 PS1 PS-1 19 4.7 for a 448-amino acid protein sharing 67% sequence homology with PS-1 protein 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252957 11173059 346659 17462 9509 PSEN2 PS2 PS-2 5 3.4 Two missense mutations of the PS-2 gene have been identified to date and are associated with 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9509|PSEN2|5664|Complete__20642|TAS2R64P|338412|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252958 11173059 346660 17461 9508 PSEN1 PS1 PS-1 7 4.7 The high degree of sequence homology between PS-1 and PS-2 protein implies similar functions and indirect evidence suggests 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252959 11173059 346660 17462 9509 PSEN2 PS2 PS-2 9 3.4 The high degree of sequence homology between PS-1 and PS-2 protein implies similar functions and indirect evidence suggests that they 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9509|PSEN2|5664|Complete__20642|TAS2R64P|338412|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252960 11173059 346660 926 620 APP amyloid amyloid 28 17.4 they may act as or cooperate with _amp_#x3b3 -secretase in amyloid precursor protein processing ( Selkoe 1999 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252961 11173059 346661 926 620 APP amyloid amyloid 12 17.4 a wide consensus on the hypothesis that missense mutations of amyloid precursor protein PS-1 and PS-2 genes may share a common 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252962 11173059 346661 17461 9508 PSEN1 PS1 PS-1 15 4.7 on the hypothesis that missense mutations of amyloid precursor protein PS-1 and PS-2 genes may share a common pathogenetic mechanism finally 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252963 11173059 346661 17462 9509 PSEN2 PS2 PS-2 17 3.4 hypothesis that missense mutations of amyloid precursor protein PS-1 and PS-2 genes may share a common pathogenetic mechanism finally leading to 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9509|PSEN2|5664|Complete__20642|TAS2R64P|338412|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252964 11173059 346661 926 620 APP amyloid amyloid 31 17.4 common pathogenetic mechanism finally leading to the accumulation of _amp_#x3b2 -amyloid protein as a byproduct of abnormal amyloid precursor protein metabolism 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252965 11173059 346661 926 620 APP amyloid amyloid 38 17.4 accumulation of _amp_#x3b2 -amyloid protein as a byproduct of abnormal amyloid precursor protein metabolism ( Selkoe 1999 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252966 11173059 346663 17461 9508 PSEN1 PS1 PS-1 10 4.7 Homozygotic polymorphism at the level of intron 8 of the PS-1 gene was first reported to double the risk of late-onset 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252967 11173059 346664 17461 9508 PSEN1 PS1 PS-1 17 4.7 others did not and a meta-analysis concluded that such a PS-1 gene polymorphism is only slightly associated with Alzheimer disease ( 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252968 11173059 346665 17461 9508 PSEN1 PS1 PS-1 9 4.7 Other polymorphisms in the 5_amp_#x2032 regulatory region of the PS-1 gene have also been detected and are associated with a 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252969 11173059 346665 17461 9508 PSEN1 PS1 PS-1 35 4.7 Alzheimer disease probably mediated by an altered expression of the PS-1 protein ( van Duijn et al. 1999 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252970 11173059 346666 17462 9509 PSEN2 PS2 PS-2 5 3.4 To date polymorphisms of the PS-2 gene have not been associated with Alzheimer disease 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9509|PSEN2|5664|Complete__20642|TAS2R64P|338412|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252971 11173059 346668 926 620 APP amyloid amyloid 9 17.4 Experimental data for transgenic mice which overexpress mutant human amyloid precursor protein and develop Alzheimer-like pathology demonstrated that immunization with 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252972 11173059 346668 926 620 APP amyloid amyloid 20 17.4 protein and develop Alzheimer-like pathology demonstrated that immunization with _amp_#x3b2 -amyloid protein may prevent neuritic plaque formation and that peripheral administration 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252973 11173059 346668 926 620 APP amyloid amyloid 32 17.4 prevent neuritic plaque formation and that peripheral administration of anti-_amp_#x3b2 -amyloid protein antibodies reduces neuritic plaque burden ( Schenk and Bard 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252974 11173059 346669 926 620 APP amyloid amyloid 12 17.4 humans are currently underway and if safe immunization with _amp_#x3b2 -amyloid protein may become the first-line treatment for asymptomatic subjects with 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252975 11173059 346671 926 620 APP amyloid amyloid 24 17.4 treatment for patients with Alzheimer disease carrying mutations of the amyloid precursor protein PS1 or PS2 gene 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252976 11173059 346671 17461 9508 PSEN1 PS1 PS1 27 0.9 with Alzheimer disease carrying mutations of the amyloid precursor protein PS1 or PS2 gene 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252977 11173059 346671 17462 9509 PSEN2 PS2 PS2 29 1.4 disease carrying mutations of the amyloid precursor protein PS1 or PS2 gene 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9509|PSEN2|5664|Complete__20642|TAS2R64P|338412|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 252978 11173059 346674 912 613 APOE APOE ApoE 24 2.4 the analysis of allele polymorphism of the apolipoprotein E (ApoE) ApoE gene 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252979 11173059 346675 912 613 APOE APOE ApoE 1 2.4 The ApoE gene maps on chromosome 19q12-q13 and contains three common coding 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252980 11173059 346677 912 613 APOE APOE ApoE 0 2.4 ApoE 4 is neither necessary nor sufficient to cause Alzheimer disease 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252981 11173059 346678 912 613 APOE APOE ApoE 10 2.4 However the increased risk of developing Alzheimer disease provided by ApoE 4 may be due to its higher affinity for _amp_#x3b2 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252982 11173059 346678 926 620 APP amyloid amyloid 20 17.4 4 may be due to its higher affinity for _amp_#x3b2 -amyloid protein compared to other alleles and to its propensity to 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252983 11173059 346678 926 620 APP amyloid amyloid 39 17.4 to enhance the aggregation or reduce the clearance of _amp_#x3b2 -amyloid protein ( Selkoe 1999 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252984 11173059 346679 912 613 APOE APOE ApoE 12 2.4 at position _amp_#x2212 491 in the 5_amp_#x2032 -promoter region of ApoE has been reported to be associated with an increased risk 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252985 11173059 346680 912 613 APOE APOE ApoE 13 2.4 _amp_#x2212 491 polymorphism appears to be independent of that of ApoE 4 and is associated with a rise in ApoE plasma 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252986 11173059 346680 912 613 APOE APOE ApoE 22 2.4 of ApoE 4 and is associated with a rise in ApoE plasma levels ( Laws et al. 1999 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252987 11173059 346683 926 620 APP amyloid amyloid 10 17.4 of them code for proteins which may participate in _amp_#x3b2 -amyloid protein processing or aggregation in neuritic plaques -1-Antichymotrypsin is a 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252988 11173059 346683 926 620 APP amyloid amyloid 30 17.4 a protease inhibitor and an acute-phase protein also found in amyloid deposits in Alzheimer disease brains ( Abraham et al. 1988 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252989 11173059 346687 926 620 APP amyloid amyloid 31 17.4 ( Licastro et al. 2000a and contribute to enhance _amp_#x3b2 -amyloid protein aggregation ( Ma et al. 1994 or hamper its 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252990 11173059 346689 926 620 APP amyloid amyloid 7 17.4 -2-Macroglobulin another proteinase inhibitor is detected in amyloid plaques and interacts with the lipoprotein receptor related protein (LRP), 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252991 11173059 346689 11988 6692 LRP1 LRP LRP 17 1.7 plaques and interacts with the lipoprotein receptor related protein (LRP), LRP as do a number of other ligands including _amp_#x3b2 -amyloid 1 JUMiner_v2.2 1 0 0 2 6502 TotalCon:4<>6692|LRP1|4035|Complete__7531|MVP|9961|Complete__9664|PTPRA|5786|Complete__6502|RPSA|3921|Complete__<>AvaiableGeneRif=4<>BEST:6502|RPSA|0.00183927560837578<>ScoreDetail__6502|RPSA|0.00183927560837578__7531|MVP|0.00128821936535479__6692|LRP1|0.00127878629576422__9664|PTPRA|0.00102267414679757__ 0 0 0 0 0 252992 11173059 346689 926 620 APP amyloid amyloid 26 17.4 LRP as do a number of other ligands including _amp_#x3b2 -amyloid protein amyloid precursor protein ApoE and cholesterol ( Rosenberg 2000 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252993 11173059 346689 926 620 APP amyloid amyloid 28 17.4 do a number of other ligands including _amp_#x3b2 -amyloid protein amyloid precursor protein ApoE and cholesterol ( Rosenberg 2000 -2-Macroglobulin also 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252994 11173059 346689 912 613 APOE APOE ApoE 31 2.4 of other ligands including _amp_#x3b2 -amyloid protein amyloid precursor protein ApoE and cholesterol ( Rosenberg 2000 -2-Macroglobulin also binds to _amp_#x3b2 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 252995 11173059 346689 926 620 APP amyloid amyloid 42 17.4 and cholesterol ( Rosenberg 2000 -2-Macroglobulin also binds to _amp_#x3b2 -amyloid protein and such complexes may be cleared through binding to 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252996 11173059 346689 11988 6692 LRP1 LRP LRP 53 1.7 protein and such complexes may be cleared through binding to LRP or deposition in amyloid plaques 1 JUMiner_v2.2 1 0 0 2 6502 TotalCon:4<>6692|LRP1|4035|Complete__7531|MVP|9961|Complete__9664|PTPRA|5786|Complete__6502|RPSA|3921|Complete__<>AvaiableGeneRif=4<>BEST:6502|RPSA|0.00183927560837578<>ScoreDetail__6502|RPSA|0.00183927560837578__7531|MVP|0.00128821936535479__6692|LRP1|0.00127878629576422__9664|PTPRA|0.00102267414679757__ 0 0 0 0 0 252997 11173059 346689 926 620 APP amyloid amyloid 57 17.4 may be cleared through binding to LRP or deposition in amyloid plaques 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252998 11173059 346690 926 620 APP amyloid amyloid 36 17.4 may reflect a genetically-determined defective removal of -2-macroglobulin/_amp_#x3b2;-amyloid -2-macroglobulin _amp_#x3b2 -amyloid protein complexes 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 252999 11173059 346691 11988 6692 LRP1 LRP LRP 0 1.7 LRP is a member of the low-density lipoprotein receptor superfamily and 1 JUMiner_v2.2 1 0 0 2 6502 TotalCon:4<>6692|LRP1|4035|Complete__7531|MVP|9961|Complete__9664|PTPRA|5786|Complete__6502|RPSA|3921|Complete__<>AvaiableGeneRif=4<>BEST:6502|RPSA|0.00183927560837578<>ScoreDetail__6502|RPSA|0.00183927560837578__7531|MVP|0.00128821936535479__6692|LRP1|0.00127878629576422__9664|PTPRA|0.00102267414679757__ 0 0 0 0 0 253000 11173059 346691 912 613 APOE APOE ApoE 19 2.4 and is believed to contribute to the clearance of ApoE/_amp_#x3b2;-amyloid ApoE _amp_#x3b2 -amyloid protein and -2-macroglobulin/_amp_#x3b2;-amyloid -2-macroglobulin _amp_#x3b2 -amyloid protein complexes 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253001 11173059 346691 926 620 APP amyloid amyloid 19 17.4 believed to contribute to the clearance of ApoE/_amp_#x3b2;-amyloid ApoE _amp_#x3b2 -amyloid protein and -2-macroglobulin/_amp_#x3b2;-amyloid -2-macroglobulin _amp_#x3b2 -amyloid protein complexes ( Hyman 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253002 11173059 346691 926 620 APP amyloid amyloid 22 17.4 of ApoE/_amp_#x3b2;-amyloid ApoE _amp_#x3b2 -amyloid protein and -2-macroglobulin/_amp_#x3b2;-amyloid -2-macroglobulin _amp_#x3b2 -amyloid protein complexes ( Hyman et al. 2000 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253003 11173059 346692 11988 6692 LRP1 LRP LRP 8 1.7 As potential candidate gene in Alzheimer disease the LRP gene was examined for DNA variations and a tetranucleotide repeat 1 JUMiner_v2.2 1 0 0 2 6502 TotalCon:4<>6692|LRP1|4035|Complete__7531|MVP|9961|Complete__9664|PTPRA|5786|Complete__6502|RPSA|3921|Complete__<>AvaiableGeneRif=4<>BEST:6502|RPSA|0.00183927560837578<>ScoreDetail__6502|RPSA|0.00183927560837578__7531|MVP|0.00128821936535479__6692|LRP1|0.00127878629576422__9664|PTPRA|0.00102267414679757__ 0 0 0 0 0 253004 11173059 346694 11988 6692 LRP1 LRP LRP 0 1.7 LRP in fact is also a receptor for cholesterol and in 1 JUMiner_v2.2 1 0 0 2 6502 TotalCon:4<>6692|LRP1|4035|Complete__7531|MVP|9961|Complete__9664|PTPRA|5786|Complete__6502|RPSA|3921|Complete__<>AvaiableGeneRif=4<>BEST:6502|RPSA|0.00183927560837578<>ScoreDetail__6502|RPSA|0.00183927560837578__7531|MVP|0.00128821936535479__6692|LRP1|0.00127878629576422__9664|PTPRA|0.00102267414679757__ 0 0 0 0 0 253005 11173059 346694 926 620 APP amyloid amyloid 28 17.4 by lovastatin and methyl-_amp_#x3b2 -cyclodextrine inhibits the production of _amp_#x3b2 -amyloid protein by cultured hippocampal neurons ( Simons et al. 1998 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253006 11173059 346695 11988 6692 LRP1 LRP LRP 15 1.7 a potential treatment for patients with Alzheimer disease carrying certain LRP genotypes ( Table 4 1 JUMiner_v2.2 1 0 0 2 6502 TotalCon:4<>6692|LRP1|4035|Complete__7531|MVP|9961|Complete__9664|PTPRA|5786|Complete__6502|RPSA|3921|Complete__<>AvaiableGeneRif=4<>BEST:6502|RPSA|0.00183927560837578<>ScoreDetail__6502|RPSA|0.00183927560837578__7531|MVP|0.00128821936535479__6692|LRP1|0.00127878629576422__9664|PTPRA|0.00102267414679757__ 0 0 0 0 0 253007 11173059 346696 912 613 APOE APOE ApoE-containing 20 1.3 density lipoprotein (VLDL) VLDL receptor functions as a receptor for ApoE-containing lipoproteins and for this reason it has been hypothesized to 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253008 11173059 346699 12369 6893 MAPT tau tau 32 1.7 et al. 1999a angiotensin-converting enzyme ( Kehoe et al. 1999 tau protein ( Lilius et al. 1999 and bleomycin hydrolase ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253009 11173059 346704 14373 7808 NGF NGF NGF 7 1.2 The trophic activity of nerve growth factor (NGF) NGF on cholinergic basal forebrain neurons ( Scott and Crutcher 1994 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253010 11173059 346705 14373 7808 NGF NGF NGF 0 1.2 NGF levels are increased in cortical areas of brains from patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253011 11173059 346705 14373 7808 NGF NGF NGF 20 1.2 patients with established Alzheimer disease whereas the number of high-affinity NGF receptors is decreased in the basal forebrain ( Hock et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253012 11173059 346706 14738 8031 NTRK1 TRKA trkA 7 1.6 A reduction in the number of high-affinity trkA receptors might mediate the loss of NGF trophic activity through 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253013 11173059 346706 14373 7808 NGF NGF NGF 14 1.2 number of high-affinity trkA receptors might mediate the loss of NGF trophic activity through impaired retrograde axonal transport ( Mufson et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253014 11173059 346707 14373 7808 NGF NGF NGF 8 1.2 Furthermore indirect but compelling evidence in favor of NGF involvement in the pathogenesis of Alzheimer disease comes from a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253015 11173059 346707 926 620 APP amyloid amyloid 35 17.4 a neutralizing anti-NGF recombinant antibody developed an Alzheimer-like pathology including amyloid plaques and neurofibrillary tangles ( Capsoni et al. 2000 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253016 11173059 346708 14373 7808 NGF NGF NGF 5 1.2 Because of the inability of NGF to cross the blood_amp_#x2013 brain barrier NGF-mimetic drugs (e.g., e.g. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253017 11173059 346708 14373 7808 NGF NGF NGF-mimetic 11 1.2 the inability of NGF to cross the blood_amp_#x2013 brain barrier NGF-mimetic drugs (e.g., e.g. Neotrofin or AIT-082 have been engineered and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253018 11173059 346710 926 620 APP amyloid amyloid 24 17.4 1999 and insulin-like growth factor-1 shows protective effects against _amp_#x3b2 -amyloid protein neurotoxicity ( Dore et al. 1999 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253019 11173059 346711 926 620 APP amyloid amyloid 11 17.4 1 exhibits opposing activities because it protects neurons against _amp_#x3b2 -amyloid protein toxicity ( Prehn et al. 1996 but enhances _amp_#x3b2 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253020 11173059 346711 926 620 APP amyloid amyloid 22 17.4 protein toxicity ( Prehn et al. 1996 but enhances _amp_#x3b2 -amyloid protein deposition in amyloid precursor protein transgenic mice ( Wyss-Coray 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253021 11173059 346711 926 620 APP amyloid amyloid 26 17.4 et al. 1996 but enhances _amp_#x3b2 -amyloid protein deposition in amyloid precursor protein transgenic mice ( Wyss-Coray et al. 1997 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253022 11173059 346713 926 620 APP amyloid amyloid 23 17.4 in vitro ( Mattson et al. 1997 and reduces _amp_#x3b2 -amyloid protein production ( Xu et al. 1998 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253023 11173059 346721 926 620 APP amyloid amyloid 16 17.4 formation of Alzheimer disease plaques by upregulating the secretion of amyloid precursor protein ( Rogers et al. 1999 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253024 11173059 346722 926 620 APP amyloid amyloid 7 17.4 Therefore a self-amplifying circuit may occur between _amp_#x3b2 -amyloid protein and cytokines ultimately fostering the sustained formation of plaques 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253025 11173059 346728 912 613 APOE APOE ApoE 24 2.4 of Alzheimer disease (i.e., i.e. siblings of Alzheimer disease patients ApoE 4 carriers and bearing specific polymorphisms of cytokine genes 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253026 11173059 346738 912 613 APOE APOE ApoE 31 2.4 risk of Alzheimer disease ( Li and Li whereas the ApoE genotype seems to affect the response to acetylcholinesterase inhibitors ( 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253027 11173059 346743 926 620 APP amyloid amyloid 19 17.4 obscure but several data suggest that chronic deposition of _amp_#x3b2 -amyloid protein may be crucial _amp_#x3b2 -Amyloid protein up-regulates pro-apoptotic molecules 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253028 11173059 346743 1576 990 BCL2 Bcl-2 Bcl-2 37 1.0 pro-apoptotic molecules such as Bax down-regulates anti-apoptotic molecules such as Bcl-2 and induces caspase enzymes ( Paradis Harada and Troy 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253029 11173059 346744 926 620 APP amyloid amyloid 5 17.4 In turn caspases may support _amp_#x3b2 -amyloid protein synthesis by altering the normal proteolytic pathway of amyloid 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253030 11173059 346744 926 620 APP amyloid amyloid 15 17.4 -amyloid protein synthesis by altering the normal proteolytic pathway of amyloid precursor protein ( Wellington and Hayden 2000 contributing to the 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253031 11173059 346744 926 620 APP amyloid amyloid 43 17.4 to the accumulation and ultimately to the aggregation of _amp_#x3b2 -amyloid protein into fibrils 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253032 11173059 346745 17461 9508 PSEN1 PS1 PS-1 3 4.7 In addition mutated PS-1 may promote apoptosis independently of _amp_#x3b2 -amyloid protein intervention by 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 253033 11173059 346745 926 620 APP amyloid amyloid 9 17.4 In addition mutated PS-1 may promote apoptosis independently of _amp_#x3b2 -amyloid protein intervention by down-regulating neuronal survival factors ( Weihl et 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 253415 11220737 347228 20996 11179 SOD1 SOD1 mSOD1 6 1.4 Mutations in the copper/zinc copper zinc superoxide dismutase (mSOD1) mSOD1 gene are associated with a familial form of amyotrophic lateral 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253416 11220737 347228 20996 11179 SOD1 ALS ALS 18 1.4 associated with a familial form of amyotrophic lateral sclerosis (ALS), ALS and their expression in transgenic mice produces an ALS-like syndrome 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160441276767528<>ScoreDetail__5468|IGFALS|0.000785571667048542__11179|SOD1|0.00160441276767528__ 0 0 0 0 0 253417 11220737 347228 20996 11179 SOD1 ALS ALS-like 27 1.4 (ALS), ALS and their expression in transgenic mice produces an ALS-like syndrome 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160441276767528<>ScoreDetail__5468|IGFALS|0.000785571667048542__11179|SOD1|0.00160441276767528__ 0 0 0 0 0 253418 11220737 347229 20996 11179 SOD1 ALS ALS 18 1.4 in the progression and propagation of the neurodegenerative process in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160441276767528<>ScoreDetail__5468|IGFALS|0.000785571667048542__11179|SOD1|0.00160441276767528__ 0 0 0 0 0 253419 11220737 347230 17610 9605 PTGS2 COX-2 Cox-2 21 1.8 of the disease the expression of cyclooxygenase type 2 (Cox-2), Cox-2 a key enzyme in the synthesis of prostanoids which are 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253420 11220737 347231 20996 11179 SOD1 SOD1 mSOD1 7 1.4 In both early symptomatic and end-stage transgenic mSOD1 mice neurons and to a lesser extent glial cells in 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253421 11220737 347231 17610 9605 PTGS2 COX-2 Cox-2 27 1.8 in the anterior horn of the spinal cord exhibit robust Cox-2 immunoreactivity 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253422 11220737 347232 17610 9605 PTGS2 COX-2 Cox-2 0 1.8 Cox-2 mRNA and protein levels and catalytic activity are also significantly 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253423 11220737 347232 20996 11179 SOD1 SOD1 mSOD1 19 1.4 also significantly increased in the spinal cord of the transgenic mSOD1 mice 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253424 11220737 347233 17610 9605 PTGS2 COX-2 Cox-2 7 1.8 The time course of the spinal cord Cox-2 upregulation parallels that of motor neuronal loss in transgenic mSOD1 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253425 11220737 347233 20996 11179 SOD1 SOD1 mSOD1 17 1.4 Cox-2 upregulation parallels that of motor neuronal loss in transgenic mSOD1 mice 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253426 11220737 347234 17610 9605 PTGS2 COX-2 Cox-2 4 1.8 We also show that Cox-2 activity is dramatically increased in postmortem spinal cord samples from 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253427 11220737 347234 20996 11179 SOD1 ALS ALS 16 1.4 is dramatically increased in postmortem spinal cord samples from sporadic ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160441276767528<>ScoreDetail__5468|IGFALS|0.000785571667048542__11179|SOD1|0.00160441276767528__ 0 0 0 0 0 253428 11220737 347235 17610 9605 PTGS2 COX-2 Cox-2 3 1.8 We speculate that Cox-2 upregulation through its pivotal role in inflammation is instrumental in 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253429 11220737 347235 20996 11179 SOD1 ALS ALS 15 1.4 through its pivotal role in inflammation is instrumental in the ALS neurodegenerative process and that Cox-2 inhibition may be a valuable 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160441276767528<>ScoreDetail__5468|IGFALS|0.000785571667048542__11179|SOD1|0.00160441276767528__ 0 0 0 0 0 253430 11220737 347235 17610 9605 PTGS2 COX-2 Cox-2 20 1.8 inflammation is instrumental in the ALS neurodegenerative process and that Cox-2 inhibition may be a valuable therapeutic avenue for the treatment 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 253431 11220737 347235 20996 11179 SOD1 ALS ALS 32 1.4 may be a valuable therapeutic avenue for the treatment of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160441276767528<>ScoreDetail__5468|IGFALS|0.000785571667048542__11179|SOD1|0.00160441276767528__ 0 0 0 0 0 247362 11458198 336764 20996 11179 SOD1 ALS ALS 28 0.0 MS rheumatoid arthritis (RA) RA and amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000792414116827246<>ScoreDetail__5468|IGFALS|0.000516457788183446__11179|SOD1|0.000792414116827246__ 0 0 0 0 0 247363 11458198 336765 9590 5164 HPSE HPA HPA 11 0.0 discuss the role of inflammation-induced changes in the hypothalamus-pituitary-adrenal (HPA) HPA axis as a possible explanation of fatigue depression and other 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 234252 11796754 317529 20996 11179 SOD1 SOD1 SOD1 13 2.2 inflammation- and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 234253 11796754 317530 20996 11179 SOD1 SOD1 SOD1 10 2.2 sclerosis (FALS)-linked FALS -linked mutations in copper-zinc superoxide dismutase (SOD1) SOD1 cause motor neuron death through one or more acquired toxic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 234254 11796754 317531 20996 11179 SOD1 SOD1 SOD1 16 2.2 motor neuron degeneration in the transgenic mouse model expressing the SOD1 gene with G93A mutation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 234255 11796754 317532 22551 11892 TNF TNF-alpha TNF-alpha 47 2.7 an inflammatory process such as the tumor necrosis factor-alpha (TNF-alpha) TNF-alpha gene resulting from glial cell activation together with the change 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 234256 11796754 317535 20996 11179 SOD1 ALS ALS 1 1.7 Thus ALS has paralleled other neurodegenerative disorders such as Alzheimer's and prion 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00221178824730383<>ScoreDetail__5468|IGFALS|0.0005781600057816__11179|SOD1|0.00221178824730383__ 0 0 0 0 0 235270 11847479 319127 22551 11892 TNF TNF TNF 3 1.2 Tumor necrosis factor (TNF) TNF has been implicated in the pathogenesis of various central nervous 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 235271 11847479 319128 22551 11892 TNF TNF TNF 1 1.2 Elevated TNF levels were observed in animal models of motor neuron disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 235272 11847479 319128 22551 11892 TNF TNF TNF 17 1.2 of motor neuron disease (MND), MND and activation of the TNF system has been reported in patients with amyotrophic lateral sclerosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 235273 11847479 319128 20996 11179 SOD1 ALS ALS 28 0.9 has been reported in patients with amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000729766818348876<>ScoreDetail__5468|IGFALS|0.000714876965911656__11179|SOD1|0.000729766818348876__ 0 0 0 0 0 235274 11847479 319129 20996 11179 SOD1 ALS ALS 31 0.9 patients to ask whether anti-TNF therapy might be beneficial in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000729766818348876<>ScoreDetail__5468|IGFALS|0.000714876965911656__11179|SOD1|0.000729766818348876__ 0 0 0 0 0 235275 11847479 319130 22551 11892 TNF TNF TNF 7 1.2 This review discusses the possible role of TNF in motoneuronal degeneration 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 235276 11847479 319131 22551 11892 TNF TNF TNF 1 1.2 Although TNF is mostly regarded as neurotoxic cytokine there are reports of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 235277 11847479 319132 20996 11179 SOD1 ALS ALS 5 0.9 Studies with animal models of ALS are not sufficient to show whether TNF has a pathogenic 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000729766818348876<>ScoreDetail__5468|IGFALS|0.000714876965911656__11179|SOD1|0.000729766818348876__ 0 0 0 0 0 235278 11847479 319132 22551 11892 TNF TNF TNF 12 1.2 animal models of ALS are not sufficient to show whether TNF has a pathogenic or a protective role in MND though 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 235279 11847479 319133 22551 11892 TNF TNF TNF-deficient 5 1.2 On the other hand while TNF-deficient mice are protected from EAE anti-TNF antibodies worsen the disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 226652 12043837 303674 18230 17440 RFWD2 COP1 Cop-1 7 0.0 Candidate vaccines were the safe synthetic copolymer Cop-1 known to cross-react with self-antigens or altered myelin-derived peptides 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 227518 12060810 305721 20996 11179 SOD1 ALS ALS 18 1.7 of selective motor neuron death during amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227519 12060810 305722 20996 11179 SOD1 ALS ALS 23 1.7 this tetracycline derivative in the G93A mice model for familial ALS was tested 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227520 12060810 305725 20996 11179 SOD1 ALS ALS 14 1.7 interference with immuno-inflammatory responses has a beneficial effect in the ALS mice model suggesting this to be a potential new strategy 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227521 12060810 305725 20996 11179 SOD1 ALS ALS 27 1.7 suggesting this to be a potential new strategy to treat ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227522 12060810 305729 14535 7873 NOS2A iNOS iNOS 11 1.9 inhibits microglial activation caspase-1 and inducible nitric oxide synthetase (iNOS) iNOS up-regulation and decreases infarct size after experimental ischemia in rats 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 227523 12060810 305730 14535 7873 NOS2A iNOS iNOS 8 1.9 Second minocycline inhibits caspase-1 and caspase-3 expression decreases iNOS activity and delays mortality in a transgenic mouse model of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 227524 12060810 305732 14535 7873 NOS2A iNOS iNOS 3 1.9 Excitotoxicity microglial activation iNOS and caspase up-regulation have all been suggested to play a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 227525 12060810 305732 20996 11179 SOD1 ALS ALS 24 1.7 in the motor neuron degeneration during amyotrophic lateral sclerosis (ALS) ALS _amp_#91 7 _amp_#93 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227526 12060810 305734 20996 11179 SOD1 ALS ALS 1 1.7 Familial ALS accounts for 10_amp_#37 of all cases and mutations of the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227527 12060810 305734 20996 11179 SOD1 SOD1 SOD1 16 2.2 all cases and mutations of the superoxide dismutase 1 ( SOD1 gene have been identified in about 20_amp_#37 of the familial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 227528 12060810 305735 20996 11179 SOD1 SOD1 SOD1 5 2.2 Transgenic mice over-expressing the human SOD1 gene with a mutation identified in ALS patients develop an 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 227529 12060810 305735 20996 11179 SOD1 ALS ALS 12 1.7 over-expressing the human SOD1 gene with a mutation identified in ALS patients develop an adult-onset progressive motor deterioration _amp_#91 8 _amp_#93 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227530 12060810 305737 20996 11179 SOD1 ALS ALS 24 1.7 microglia in particular may contribute to the disease progression in ALS _amp_#91 9 10 _amp_#93 we tested the therapeutic efficacy of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227531 12060810 305737 20996 11179 SOD1 ALS ALS 41 1.7 therapeutic efficacy of minocycline on the G93A mice model for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227532 12060810 305738 20996 11179 SOD1 SOD1 SOD1 6 2.2 Transgenic mice with the G93A human SOD1 mutation TgN(SOD1-G93A)G1H, TgN SOD1-G93A G1H were obtained from The Jackson 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 227533 12060810 305738 22055 11764 TG TGN TgN 8 0.1 Transgenic mice with the G93A human SOD1 mutation TgN(SOD1-G93A)G1H, TgN SOD1-G93A G1H were obtained from The Jackson Laboratories (Bar Bar 6 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 227534 12060810 305759 20996 11179 SOD1 ALS ALS 10 1.7 In order to evaluate the potential benefit of minocycline in ALS G93A transgenic mice were treated from day 70 until death 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227535 12060810 305777 14535 7873 NOS2A iNOS iNOS 22 1.9 microglia as well as the concomitant induction of caspase-1 and iNOS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 227536 12060810 305778 14535 7873 NOS2A iNOS iNOS 35 1.9 related to an inhibition of caspases and a decrease in iNOS activity _amp_#91 5 _amp_#93 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 227537 12060810 305780 12337 6871 MAPK1 p38 p38 27 1.7 and proliferation of microglia induced by excitotoxicity by inhibiting the p38 mitogen-activated protein kinase (p38 p38 MAPK _amp_#91 6 _amp_#93 1 JUMiner_v2.2 1 0 0 2 6871 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6871|MAPK1|0.000532909628940679<>ScoreDetail__1189|AHSA1|0.000113378684807256__6878|MAPK4|0.000348234531908001__6871|MAPK1|0.000532909628940679__6876|MAPK14|0.000492391301403078__ 0 0 0 0 0 227538 12060810 305780 12337 6871 MAPK1 p38 p38 31 1.7 by excitotoxicity by inhibiting the p38 mitogen-activated protein kinase (p38 p38 MAPK _amp_#91 6 _amp_#93 1 JUMiner_v2.2 1 0 0 2 6871 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6871|MAPK1|0.000532909628940679<>ScoreDetail__1189|AHSA1|0.000113378684807256__6878|MAPK4|0.000348234531908001__6871|MAPK1|0.000532909628940679__6876|MAPK14|0.000492391301403078__ 0 0 0 0 0 227539 12060810 305780 12337 6871 MAPK1 MAPK MAPK 32 2.0 excitotoxicity by inhibiting the p38 mitogen-activated protein kinase (p38 p38 MAPK _amp_#91 6 _amp_#93 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 227540 12060810 305781 20996 11179 SOD1 ALS ALS 18 1.7 microglial activation might actively contribute to the disease progression during ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227541 12060810 305782 20996 11179 SOD1 ALS ALS 20 1.7 microglia both in patients _amp_#91 12 _amp_#93 and in mutant ALS mice _amp_#91 9 13 _amp_#93 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227542 12060810 305793 6869 3518 EXTL3 RPR RPR 1 0.0 For RPR 119990 _amp_#91 21 _amp_#93 and riluzole _amp_#91 22 _amp_#93 the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 227543 12060810 305795 20996 11179 SOD1 ALS ALS 18 1.7 and important protection in the transgenic mice model of familial ALS most likely by inhibition of the microglial activation that coincides 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 227544 12060810 305796 20996 11179 SOD1 ALS ALS 25 1.7 to test whether it could be an effective treatment for ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00161246018171857<>ScoreDetail__5468|IGFALS|0.000561482313307131__11179|SOD1|0.00161246018171857__ 0 0 0 0 0 229345 12124437 309219 20996 11179 SOD1 SOD1 SOD1 14 1.4 often caused by gain-of-function mutations in Cu Zn-superoxide dismutase (SOD1) SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 229346 12124437 309220 20996 11179 SOD1 SOD1 SOD1 26 1.4 genes in spinal cords of mice that ubiquitously express human SOD1 bearing a glycine (r) r alanine substitution at residue 93 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 229347 12124437 309220 18741 10289 RPA1 RPA RPAs 4 0.0 Multiprobe ribonuclease protection assays (RPAs) RPAs were used to investigate expression of 36 different cytokines and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 229348 12124437 309222 10437 5992 IL1B IL1B IL1beta 17 0.3 of macrophage-typical cytokines (monokines) monokines including interleukin (IL)1alpha, IL 1alpha IL1beta and IL1RA at 80 days increasing by 120 days 12 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 229349 12124437 309222 10444 5993 IL1R1 IL1RA IL1RA 19 1.3 cytokines (monokines) monokines including interleukin (IL)1alpha, IL 1alpha IL1beta and IL1RA at 80 days increasing by 120 days 1 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000282112714493562<>ScoreDetail__5993|IL1R1|0.000249396198676888__6000|IL1RN|0.000282112714493562__ 0 0 0 0 0 229350 12124437 309223 10452 6001 IL2 IL2 IL2 6 0.3 Contrastingly T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 were detected at low levels in non-transgenic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 229351 12124437 309223 10456 6011 IL3 IL3 IL3 7 0.3 Contrastingly T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 were detected at low levels in non-transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 229352 12124437 309223 10458 6014 IL4 IL4 IL4 7 0.3 Contrastingly T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 were detected at low levels in non-transgenic mice 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 229353 12124437 309223 10458 6014 IL4 IL4 IL4 9 0.3 Contrastingly T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 were detected at low levels in non-transgenic mice but these 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 229354 12124437 309224 6920 3573 FADD FADD FADD 24 1.6 components were up-regulated at 120 days the only exceptions being FADD and the tumor necrosis factor (TNF)alpha TNF alpha receptor p55 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 229355 12124437 309224 22551 11892 TNF TNF TNF 30 1.2 only exceptions being FADD and the tumor necrosis factor (TNF)alpha TNF alpha receptor p55 which was up-regulated at 80 days and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 229356 12124437 309224 22561 11916 TNFRSF1A p55 p55 32 1.2 FADD and the tumor necrosis factor (TNF)alpha TNF alpha receptor p55 which was up-regulated at 80 days and increased further at 1 JUMiner_v2.2 1 0 0 2 8981 TotalCon:5<>8981|PIK3R3|8503|Complete__9557|PSMD12|5718|No_GeneRif__3446|ERG|2078|Complete__11148|FSCN1|6624|Complete__11916|TNFRSF1A|7132|Complete__<>AvaiableGeneRif=4<>BEST:8981|PIK3R3|0.000819288389513109<>ScoreDetail__11916|TNFRSF1A|0.00078456639557487__3446|ERG|0.000646585904427283__11148|FSCN1|0.000542546116419896__8981|PIK3R3|0.000819288389513109__ 0 0 0 0 0 229357 12124437 309225 22551 11892 TNF TNFalpha TNFalpha 33 1.2 cytokine expression in FALS are likely minor and (iii) iii TNFalpha and its receptors may link inflammation to apoptosis in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 229358 12124437 309225 20996 11179 SOD1 ALS ALS 43 1.4 TNFalpha and its receptors may link inflammation to apoptosis in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00139476846555297<>ScoreDetail__5468|IGFALS|0.000546761803220427__11179|SOD1|0.00139476846555297__ 0 0 0 0 0 229973 12137643 310084 9947 5468 IGFALS ALS ALS 16 2.1 was change in disease progression as determined by the Appel ALS Rating Scale total score with 0.1 mg/kg/day mg kg day 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00199497735113948<>ScoreDetail__5468|IGFALS|0.00199497735113948__11179|SOD1|0.00112775227220435__ 0 0 0 0 0 223774 12194501 299400 20996 11179 SOD1 ALS ALS 32 1.4 disorders such as forms of familial amyotrophic lateral sclerosis (ALS) ALS and glutathione peroxidase-linked adolescent seizures Parkinson's disease and Alzheimer's dementia 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00111673933487219<>ScoreDetail__5468|IGFALS|0.000380170316301703__11179|SOD1|0.00111673933487219__ 0 0 0 0 0 223775 12194501 299401 20996 11179 SOD1 SOD SOD 25 1.7 expression/activity expression activity of its endogenous scavenger superoxide dismutase (SOD), SOD as a common denominator 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 223776 12194501 299402 20996 11179 SOD1 SOD SOD 6 1.7 This review summarizes the function of SOD under normal physiological conditions as well as its role in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 223777 12194501 299403 20996 11179 SOD1 SOD SOD 20 1.7 knockouts in antioxidant enzyme/protein enzyme protein levels and the genetic SOD mutations observed in some familial cases of ALS are also 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 223778 12194501 299403 20996 11179 SOD1 ALS ALS 28 1.4 the genetic SOD mutations observed in some familial cases of ALS are also discussed 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00111673933487219<>ScoreDetail__5468|IGFALS|0.000380170316301703__11179|SOD1|0.00111673933487219__ 0 0 0 0 0 224941 12270689 301344 20996 11179 SOD1 ALS ALS 11 1.7 currently no effective pharmacological treatment for amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00203055323719497<>ScoreDetail__5468|IGFALS|0.000443602048634916__11179|SOD1|0.00203055323719497__ 0 0 0 0 0 224942 12270689 301345 20996 11179 SOD1 ALS ALS 15 1.7 secondary inflammation and caspase activation may contribute to neurodegeneration in ALS we tested the effects of minocycline a second-generation tetracycline with 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00203055323719497<>ScoreDetail__5468|IGFALS|0.000443602048634916__11179|SOD1|0.00203055323719497__ 0 0 0 0 0 224943 12270689 301345 20996 11179 SOD1 SOD1 SOD1 35 1.7 anti-inflammatory properties in mice expressing a mutant superoxide dismutase (SOD1(G37R)) SOD1 G37R linked to human ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 224944 12270689 301345 20996 11179 SOD1 ALS ALS 39 1.7 a mutant superoxide dismutase (SOD1(G37R)) SOD1 G37R linked to human ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00203055323719497<>ScoreDetail__5468|IGFALS|0.000443602048634916__11179|SOD1|0.00203055323719497__ 0 0 0 0 0 224945 12270689 301346 20996 11179 SOD1 SOD1 SOD1 33 1.7 muscle strength decline and it increased the longevity of SOD1(G37R) SOD1 G37R mice by approximately 5 weeks for approximately 70% of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 224946 12270689 301347 20996 11179 SOD1 SOD1 SOD1 25 1.7 end stage of disease in the spinal cord of SOD1(G37R) SOD1 G37R mice treated with minocycline 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 224947 12270689 301348 20996 11179 SOD1 ALS ALS 20 1.7 may represent a novel and effective drug for treatment of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00203055323719497<>ScoreDetail__5468|IGFALS|0.000443602048634916__11179|SOD1|0.00203055323719497__ 0 0 0 0 0 226013 12362410 302429 20996 11179 SOD1 ALS ALS 15 0.0 the brainstem and spinal cord of amyotrophic lateral sclerosis (ALS) ALS cases and in mouse models of the disease 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00103312875457412<>ScoreDetail__5468|IGFALS|0.000205613241492752__11179|SOD1|0.00103312875457412__ 0 0 0 0 0 226014 12362410 302431 17610 9605 PTGS2 COX-2 COX-2 33 1.0 and a sharp upregulation of the enzyme cyclooxygenase 2 (COX-2) COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 226015 12362410 302432 20996 11179 SOD1 ALS ALS 10 0.0 Anti-inflammatory agents may have a role to play in treating ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00103312875457412<>ScoreDetail__5468|IGFALS|0.000205613241492752__11179|SOD1|0.00103312875457412__ 0 0 0 0 0 226016 12362410 302433 17610 9605 PTGS2 COX-2 COX-2 0 1.0 COX-2 is a particularly attractive target because of its marked increase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 226017 12362410 302433 20996 11179 SOD1 ALS ALS 12 0.0 a particularly attractive target because of its marked increase in ALS spinal cord 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00103312875457412<>ScoreDetail__5468|IGFALS|0.000205613241492752__11179|SOD1|0.00103312875457412__ 0 0 0 0 0 220317 12417341 294830 18435 13432 RNF19A dorfin dorfin 16 2.4 level of the following six genes was altered in SALS dorfin metallothionein-3 30 kDa TATA-binding protein-associated factor neugrin ubiquitin-like protein 5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220318 12417341 294834 20996 11179 SOD1 ALS ALS 3 3.9 Amyotrophic lateral sclerosis (ALS) ALS is one of the most common neurodegenerative disorders characterized by 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0012197662335473<>ScoreDetail__5468|IGFALS|0.000411226482985504__11179|SOD1|0.0012197662335473__ 0 0 0 0 0 220319 12417341 294835 20996 11179 SOD1 ALS ALS 3 3.9 Approximately 10% of ALS is familial and 10_amp_#x2013 20% of these familial ALS (FALS) 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0012197662335473<>ScoreDetail__5468|IGFALS|0.000411226482985504__11179|SOD1|0.0012197662335473__ 0 0 0 0 0 220320 12417341 294835 20996 11179 SOD1 ALS ALS 11 3.9 of ALS is familial and 10_amp_#x2013 20% of these familial ALS (FALS) FALS cases are caused by missense mutations in the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0012197662335473<>ScoreDetail__5468|IGFALS|0.000411226482985504__11179|SOD1|0.0012197662335473__ 0 0 0 0 0 220321 12417341 294835 20996 11179 SOD1 SOD1 SOD1 24 3.9 missense mutations in the Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 gene 1 while others are considered to be sporadic ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220322 12417341 294835 20996 11179 SOD1 ALS ALS 36 3.9 SOD1 gene 1 while others are considered to be sporadic ALS (SALS) SALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0012197662335473<>ScoreDetail__5468|IGFALS|0.000411226482985504__11179|SOD1|0.0012197662335473__ 0 0 0 0 0 220323 12417341 294851 20996 11179 SOD1 ALS ALS 3 3.9 Diagnostic criteria for ALS were based on the El Escorial criteria outlined by the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0012197662335473<>ScoreDetail__5468|IGFALS|0.000411226482985504__11179|SOD1|0.0012197662335473__ 0 0 0 0 0 220324 12417341 294853 20996 11179 SOD1 ALS1 ALS1 3 3.9 One SALS case (ALS1) ALS1 and a control (C1) C1 were used for the molecular 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220325 12417341 294860 20996 11179 SOD1 ALS1 ALS1 1 3.9 SALS (ALS1) ALS1 and control (C1) C1 spinal cords were used for molecular 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220326 12417341 294867 20996 11179 SOD1 ALS ALS 28 3.9 cDNA fragments with an apparent difference in peak between the ALS spinal cord and control were chosen as candidate gene fragments 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0012197662335473<>ScoreDetail__5468|IGFALS|0.000411226482985504__11179|SOD1|0.0012197662335473__ 0 0 0 0 0 220327 12417341 294875 8278 4250 GGT1 GTG GTG 31 0.5 ml T7-oligo-dT primer (5_amp_#x2032;-TCT 5_amp_#x2032 -TCT AGT CGA CGG CCA GTG AAT TGT AAT ACG ACT CAC TAT AGG GCG T 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220328 12417341 294875 23798 12612 USP14 TGT TGT 33 0.6 primer (5_amp_#x2032;-TCT 5_amp_#x2032 -TCT AGT CGA CGG CCA GTG AAT TGT AAT ACG ACT CAC TAT AGG GCG T 21 -3_amp_#x2032 1 JUMiner_v2.2 1 2 35 0 1 0 TotalCon:2<>23797|QTRT1|81890|No_GeneRif__12612|USP14|9097|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 220329 12417341 294875 7572 17371 FHL5 ACT ACT 36 0.3 -TCT AGT CGA CGG CCA GTG AAT TGT AAT ACG ACT CAC TAT AGG GCG T 21 -3_amp_#x2032 at 42_amp_#xb0 C 1 JUMiner_v2.2 1 2 35 0 2 145 TotalCon:6<>24157|ACOT7|11332|Complete__17371|FHL5|9457|Complete__16|SERPINA3|12|Complete__17780|ACTBL2|345651|No_GeneRif__144|ACTG1|71|Complete__145|ACTG2|72|Complete__<>AvaiableGeneRif=5<>BEST:145|ACTG2|0.000895372811881351<>ScoreDetail__17371|FHL5|0.000809922710232795__145|ACTG2|0.000895372811881351__24157|ACOT7|0.000565426561631495__144|ACTG1|0.000314582224765653__16|SERPINA3|0.000578228402579135__ 0 0 0 0 0 220330 12417341 294875 20237 1421 SLC25A20 CAC CAC 37 0.3 AGT CGA CGG CCA GTG AAT TGT AAT ACG ACT CAC TAT AGG GCG T 21 -3_amp_#x2032 at 42_amp_#xb0 C for 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220331 12417341 294875 452 333 AGT AGT AGT 27 0.0 of 0.5 mg/ml mg ml T7-oligo-dT primer (5_amp_#x2032;-TCT 5_amp_#x2032 -TCT AGT CGA CGG CCA GTG AAT TGT AAT ACG ACT CAC 1 JUMiner_v2.2 1 0 0 2 341 TotalCon:2<>333|AGT|183|Complete__341|AGXT|189|Complete__<>AvaiableGeneRif=2<>BEST:341|AGXT|0.000452679490518535<>ScoreDetail__333|AGT|0.000350759529288421__341|AGXT|0.000452679490518535__ 0 0 0 0 0 220332 12417341 294875 4265 1885 CGA CGA CGA 28 0.0 0.5 mg/ml mg ml T7-oligo-dT primer (5_amp_#x2032;-TCT 5_amp_#x2032 -TCT AGT CGA CGG CCA GTG AAT TGT AAT ACG ACT CAC TAT 1 JUMiner_v2.2 1 0 0 2 1929 TotalCon:2<>1885|CGA|1081|Complete__1929|CHGA|1113|Complete__<>AvaiableGeneRif=2<>BEST:1929|CHGA|0.000418791508538899<>ScoreDetail__1885|CGA|0.00034398566484308__1929|CHGA|0.000418791508538899__ 0 0 0 0 0 220333 12417341 294875 7357 3604 FBN2 CCA CCA 30 0.2 mg ml T7-oligo-dT primer (5_amp_#x2032;-TCT 5_amp_#x2032 -TCT AGT CGA CGG CCA GTG AAT TGT AAT ACG ACT CAC TAT AGG GCG 5 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220334 12417341 294875 19697 8941 SERPINA1 AAT AAT 32 0.4 T7-oligo-dT primer (5_amp_#x2032;-TCT 5_amp_#x2032 -TCT AGT CGA CGG CCA GTG AAT TGT AAT ACG ACT CAC TAT AGG GCG T 21 5 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220335 12417341 294875 19697 8941 SERPINA1 AAT AAT 34 0.3 (5_amp_#x2032;-TCT 5_amp_#x2032 -TCT AGT CGA CGG CCA GTG AAT TGT AAT ACG ACT CAC TAT AGG GCG T 21 -3_amp_#x2032 at 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220336 12417341 294875 6069 23483 DOCK11 ACG ACG 35 0.4 5_amp_#x2032 -TCT AGT CGA CGG CCA GTG AAT TGT AAT ACG ACT CAC TAT AGG GCG T 21 -3_amp_#x2032 at 42_amp_#xb0 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220337 12417341 294875 21790 11573 TAT TAT TAT 38 0.3 CGA CGG CCA GTG AAT TGT AAT ACG ACT CAC TAT AGG GCG T 21 -3_amp_#x2032 at 42_amp_#xb0 C for 1 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220338 12417341 294875 8198 4191 GCG GCG GCG 40 0.0 CCA GTG AAT TGT AAT ACG ACT CAC TAT AGG GCG T 21 -3_amp_#x2032 at 42_amp_#xb0 C for 1 h in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220339 12417341 294878 20218 10979 SLC25A1 CTP CTP 35 0.3 T7 buffer 1.5 _amp_#x3bc l each of 100 mM ATP CTP GTP and UTP 2 _amp_#x3bc l 0.1 M DTT and 1 JUMiner_v2.2 1 2 ctp 0 0 0 0 0 0 0 0 220340 12417341 294878 13812 32159 MTG1 GTP GTP 36 0.2 buffer 1.5 _amp_#x3bc l each of 100 mM ATP CTP GTP and UTP 2 _amp_#x3bc l 0.1 M DTT and 2 5 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 220341 12417341 294881 19573 10691 SDS SDS SDS 26 0.0 solution of 2_amp_#xd7 Denhardt_amp_#x2019 s solution 4_amp_#xd7 SSC and 0.2% SDS 1 JUMiner_v2.2 1 0 0 2 19440 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:19440|SBDS|0.000485519059963831<>ScoreDetail__10691|SDS|0.000263546278726544__19440|SBDS|0.000485519059963831__ 0 0 0 0 0 220342 12417341 294882 19573 10691 SDS SDS SDS 8 0.0 After hybridization the arrays were washed in 2_amp_#xd7 SSC_amp_#x2013 0.1% SDS and 0.2_amp_#xd7 SSC for 20 min respectively and then rinsed 1 JUMiner_v2.2 1 0 0 2 19440 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:19440|SBDS|0.000485519059963831<>ScoreDetail__10691|SDS|0.000263546278726544__19440|SBDS|0.000485519059963831__ 0 0 0 0 0 220343 12417341 294891 8118 4141 GAPDH GAPDH GAPDH 9 1.9 For internal standard control the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) GAPDH was quantified simultaneously 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220344 12417341 294892 8118 4141 GAPDH GAPDH GAPDH 11 1.9 probe sequences (forward forward primer reverse primer and TaqMan probe GAPDH 5_amp_#x2032 -CCT GGA GAA ACC TGC CAA GTA T-3_amp_#x2032 5_amp_#x2032 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220345 12417341 294892 3839 1614 CCT CCT CCT 12 0.3 (forward forward primer reverse primer and TaqMan probe GAPDH 5_amp_#x2032 -CCT GGA GAA ACC TGC CAA GTA T-3_amp_#x2032 5_amp_#x2032 -TGA AGT 11 JUMiner_v2.2 1 2 35 1 1 0 TotalCon:2<>1614|CCT|907|No_GeneRif__20105|FLVCR2|55640|No_GeneRif__<>AvaiableGeneRif=0<> 0 0 0 0 0 220346 12417341 294892 3839 1614 CCT CCT CCT-3_amp_#x2032 26 0.3 CAA GTA T-3_amp_#x2032 5_amp_#x2032 -TGA AGT CGC AGG AGA CAA CCT-3_amp_#x2032 5_amp_#x2032 -CAT CAA GAA GGT GGT GAA GCA GGC ATC-3_amp_#x2032 11 JUMiner_v2.2 1 2 35 1 1 0 TotalCon:2<>1614|CCT|907|No_GeneRif__20105|FLVCR2|55640|No_GeneRif__<>AvaiableGeneRif=0<> 0 0 0 0 0 220347 12417341 294892 8451 13734 GLYAT CAT CAT 27 0.5 T-3_amp_#x2032 5_amp_#x2032 -TGA AGT CGC AGG AGA CAA CCT-3_amp_#x2032 5_amp_#x2032 -CAT CAA GAA GGT GGT GAA GCA GGC ATC-3_amp_#x2032 clone 1 11 JUMiner_v2.2 1 2 35 0 1 0 TotalCon:2<>1516|CAT|847|Complete__13734|GLYAT|10249|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 220348 12417341 294892 8278 4250 GGT1 GGT GGT 30 0.5 AGT CGC AGG AGA CAA CCT-3_amp_#x2032 5_amp_#x2032 -CAT CAA GAA GGT GGT GAA GCA GGC ATC-3_amp_#x2032 clone 1 5_amp_#x2032 -CCG TCA 1 JUMiner_v2.2 1 2 35 0 1 0 TotalCon:6<>4250|GGT1|2678|Complete__4251|GGT2|728441|No_GeneRif__33426|GGTLC3|728226|No_GeneRif__33428|GGTLC4P|729838|No_GeneRif__33427|GGTLC5P|653590|No_GeneRif__4252|GGT3P|2679|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 220349 12417341 294892 8278 4250 GGT1 GGT GGT 31 0.5 CGC AGG AGA CAA CCT-3_amp_#x2032 5_amp_#x2032 -CAT CAA GAA GGT GGT GAA GCA GGC ATC-3_amp_#x2032 clone 1 5_amp_#x2032 -CCG TCA CTC 1 JUMiner_v2.2 1 2 35 0 1 0 TotalCon:6<>4250|GGT1|2678|Complete__4251|GGT2|728441|No_GeneRif__33426|GGTLC3|728226|No_GeneRif__33428|GGTLC4P|729838|No_GeneRif__33427|GGTLC5P|653590|No_GeneRif__4252|GGT3P|2679|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 220350 12417341 294892 1271 795 ATM ATC ATC-3_amp_#x2032 35 0.5 CCT-3_amp_#x2032 5_amp_#x2032 -CAT CAA GAA GGT GGT GAA GCA GGC ATC-3_amp_#x2032 clone 1 5_amp_#x2032 -CCG TCA CTC AAA AGG TTG AA-3_amp_#x2032 11 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220351 12417341 294892 8278 4250 GGT1 GTG GTG 47 0.5 -CCG TCA CTC AAA AGG TTG AA-3_amp_#x2032 5_amp_#x2032 -TGG CGT GTG AAG TGA CTT TT-3_amp_#x2032 5_amp_#x2032 -AGC ATG AAG AGA CCT 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220352 12417341 294892 3839 1614 CCT CCT CCT 56 0.3 GTG AAG TGA CTT TT-3_amp_#x2032 5_amp_#x2032 -AGC ATG AAG AGA CCT TTG AGG AGA AAC TAG TG-3_amp_#x2032 clone 2 5_amp_#x2032 -AAG 11 JUMiner_v2.2 1 2 35 1 1 0 TotalCon:2<>1614|CCT|907|No_GeneRif__20105|FLVCR2|55640|No_GeneRif__<>AvaiableGeneRif=0<> 0 0 0 0 0 220353 12417341 294892 1271 795 ATM ATC ATC 84 0.5 AGG TGA AGT AG-3_amp_#x2032 5_amp_#x2032 -CTC AGC GAG TAT GGC ATC AAT GTG AAG AAG-3_amp_#x2032 clone 3 5_amp_#x2032 -TAG GAG CCA 11 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220354 12417341 294892 8278 4250 GGT1 GTG GTG 86 0.5 AGT AG-3_amp_#x2032 5_amp_#x2032 -CTC AGC GAG TAT GGC ATC AAT GTG AAG AAG-3_amp_#x2032 clone 3 5_amp_#x2032 -TAG GAG CCA TCC GAG 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220355 12417341 294892 8451 13734 GLYAT CAT CAT 99 0.5 5_amp_#x2032 -TAG GAG CCA TCC GAG ACA AC-3_amp_#x2032 5_amp_#x2032 -TAC CAT GGC ACT TCC TGA CA-3_amp_#x2032 5_amp_#x2032 -CAC TAG CTG GAG 11 JUMiner_v2.2 1 2 35 0 1 0 TotalCon:2<>1516|CAT|847|Complete__13734|GLYAT|10249|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 220356 12417341 294892 7572 17371 FHL5 ACT ACT 101 0.3 GAG CCA TCC GAG ACA AC-3_amp_#x2032 5_amp_#x2032 -TAC CAT GGC ACT TCC TGA CA-3_amp_#x2032 5_amp_#x2032 -CAC TAG CTG GAG CCA GTA 1 JUMiner_v2.2 1 2 35 0 2 145 TotalCon:6<>24157|ACOT7|11332|Complete__17371|FHL5|9457|Complete__16|SERPINA3|12|Complete__17780|ACTBL2|345651|No_GeneRif__144|ACTG1|71|Complete__145|ACTG2|72|Complete__<>AvaiableGeneRif=5<>BEST:145|ACTG2|0.000895372811881351<>ScoreDetail__17371|FHL5|0.000809922710232795__145|ACTG2|0.000895372811881351__24157|ACOT7|0.000565426561631495__144|ACTG1|0.000314582224765653__16|SERPINA3|0.000578228402579135__ 0 0 0 0 0 220357 12417341 294892 20237 1421 SLC25A20 CAC CAC 105 0.3 AC-3_amp_#x2032 5_amp_#x2032 -TAC CAT GGC ACT TCC TGA CA-3_amp_#x2032 5_amp_#x2032 -CAC TAG CTG GAG CCA GTA TAA CGG GGA-3_amp_#x2032 clone 4 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220358 12417341 294892 3839 1614 CCT CCT CCT 128 0.3 GCA GGA TCA AA-3_amp_#x2032 5_amp_#x2032 -AGG GAG CAG CTT TCA CCT AT-3_amp_#x2032 5_amp_#x2032 -AAG TCC TTA AGA AAG CTG GGC TTG 11 JUMiner_v2.2 1 2 35 1 1 0 TotalCon:2<>1614|CCT|907|No_GeneRif__20105|FLVCR2|55640|No_GeneRif__<>AvaiableGeneRif=0<> 0 0 0 0 0 220359 12417341 294892 23798 12612 USP14 TGT TGT 143 0.6 AAG CTG GGC TTG CCC AC-3_amp_#x2032 clone 5 5_amp_#x2032 -GCC TGT TCT GTC ACC ATC AA-3_amp_#x2032 5_amp_#x2032 -GCA GAG GCC ACA 1 JUMiner_v2.2 1 2 35 0 1 0 TotalCon:2<>23797|QTRT1|81890|No_GeneRif__12612|USP14|9097|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 220360 12417341 294892 1271 795 ATM ATC ATC 147 0.5 CCC AC-3_amp_#x2032 clone 5 5_amp_#x2032 -GCC TGT TCT GTC ACC ATC AA-3_amp_#x2032 5_amp_#x2032 -GCA GAG GCC ACA GGT TTA GA-3_amp_#x2032 5_amp_#x2032 11 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220361 12417341 294892 8278 4250 GGT1 GGT GGT 153 0.5 TCT GTC ACC ATC AA-3_amp_#x2032 5_amp_#x2032 -GCA GAG GCC ACA GGT TTA GA-3_amp_#x2032 5_amp_#x2032 -CCA TTC AGC AGT CCA TTG AAA 1 JUMiner_v2.2 1 2 35 0 1 0 TotalCon:6<>4250|GGT1|2678|Complete__4251|GGT2|728441|No_GeneRif__33426|GGTLC3|728226|No_GeneRif__33428|GGTLC4P|729838|No_GeneRif__33427|GGTLC5P|653590|No_GeneRif__4252|GGT3P|2679|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 220362 12417341 294892 3839 1614 CCT CCT CCT 168 0.3 AGT CCA TTG AAA GGC TCT TAG-3_amp_#x2032 clone 6 5_amp_#x2032 -CCT GTT GGA GGA GCA GAA CT-3_amp_#x2032 5_amp_#x2032 -GAA GCC ACA 11 JUMiner_v2.2 1 2 35 1 1 0 TotalCon:2<>1614|CCT|907|No_GeneRif__20105|FLVCR2|55640|No_GeneRif__<>AvaiableGeneRif=0<> 0 0 0 0 0 220363 12417341 294892 7572 17371 FHL5 ACT ACT 185 0.3 GCC ACA GAC AGC ACA GA-3_amp_#x2032 5_amp_#x2032 -AGG GCC CTA ACT ACC TGA CGG CCT GT-3_amp_#x2032 clone 7 5_amp_#x2032 -GTT GAC 1 JUMiner_v2.2 1 2 35 0 2 145 TotalCon:6<>24157|ACOT7|11332|Complete__17371|FHL5|9457|Complete__16|SERPINA3|12|Complete__17780|ACTBL2|345651|No_GeneRif__144|ACTG1|71|Complete__145|ACTG2|72|Complete__<>AvaiableGeneRif=5<>BEST:145|ACTG2|0.000895372811881351<>ScoreDetail__17371|FHL5|0.000809922710232795__145|ACTG2|0.000895372811881351__24157|ACOT7|0.000565426561631495__144|ACTG1|0.000314582224765653__16|SERPINA3|0.000578228402579135__ 0 0 0 0 0 220364 12417341 294892 3839 1614 CCT CCT CCT 189 0.3 ACA GA-3_amp_#x2032 5_amp_#x2032 -AGG GCC CTA ACT ACC TGA CGG CCT GT-3_amp_#x2032 clone 7 5_amp_#x2032 -GTT GAC CGA GCT GGA GAA 11 JUMiner_v2.2 1 2 35 1 1 0 TotalCon:2<>1614|CCT|907|No_GeneRif__20105|FLVCR2|55640|No_GeneRif__<>AvaiableGeneRif=0<> 0 0 0 0 0 220365 12417341 294892 3839 1614 CCT CCT CCT 200 0.3 7 5_amp_#x2032 -GTT GAC CGA GCT GGA GAA AG-3_amp_#x2032 5_amp_#x2032 -CCT GTA GAC GGC ATG GAA AT-3_amp_#x2032 5_amp_#x2032 -CAT CGA CGT 11 JUMiner_v2.2 1 2 35 1 1 0 TotalCon:2<>1614|CCT|907|No_GeneRif__20105|FLVCR2|55640|No_GeneRif__<>AvaiableGeneRif=0<> 0 0 0 0 0 220366 12417341 294892 8451 13734 GLYAT CAT CAT 207 0.5 AG-3_amp_#x2032 5_amp_#x2032 -CCT GTA GAC GGC ATG GAA AT-3_amp_#x2032 5_amp_#x2032 -CAT CGA CGT CTA CCA CAA GTA CTC CCT GAT-3_amp_#x2032 clone 11 JUMiner_v2.2 1 2 35 0 1 0 TotalCon:2<>1516|CAT|847|Complete__13734|GLYAT|10249|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 220367 12417341 294892 3839 1614 CCT CCT CCT 215 0.3 AT-3_amp_#x2032 5_amp_#x2032 -CAT CGA CGT CTA CCA CAA GTA CTC CCT GAT-3_amp_#x2032 clone 8 5_amp_#x2032 -AAG TGC GAG GGA TGC AAA 11 JUMiner_v2.2 1 2 35 1 1 0 TotalCon:2<>1614|CCT|907|No_GeneRif__20105|FLVCR2|55640|No_GeneRif__<>AvaiableGeneRif=0<> 0 0 0 0 0 220368 12417341 294892 8451 13734 GLYAT GAT GAT-3_amp_#x2032 216 0.5 5_amp_#x2032 -CAT CGA CGT CTA CCA CAA GTA CTC CCT GAT-3_amp_#x2032 clone 8 5_amp_#x2032 -AAG TGC GAG GGA TGC AAA T-3_amp_#x2032 11 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220369 12417341 294892 20237 1421 SLC25A20 CAC CAC 231 0.3 GGA TGC AAA T-3_amp_#x2032 5_amp_#x2032 -ACA CAG TCC TTG GCA CAC TT-3_amp_#x2032 5_amp_#x2032 -ACC TCC TGC AAG AAG AGC TGC TGC 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220370 12417341 294892 8451 13734 GLYAT GAT GAT 246 0.5 AAG AGC TGC TGC TC-3_amp_#x2032 clone 9 5_amp_#x2032 -TCC CTT GAT CCC ACA AGT TC-3_amp_#x2032 5_amp_#x2032 -ACA GGC ATA CAC CAC 11 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220371 12417341 294892 1271 795 ATM ATA ATA 253 0.5 -TCC CTT GAT CCC ACA AGT TC-3_amp_#x2032 5_amp_#x2032 -ACA GGC ATA CAC CAC CAC AT-3_amp_#x2032 5_amp_#x2032 -AGG CAG CAT AGT GAG 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220372 12417341 294892 20237 1421 SLC25A20 CAC CAC 254 0.3 CTT GAT CCC ACA AGT TC-3_amp_#x2032 5_amp_#x2032 -ACA GGC ATA CAC CAC CAC AT-3_amp_#x2032 5_amp_#x2032 -AGG CAG CAT AGT GAG ACC 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220373 12417341 294892 20237 1421 SLC25A20 CAC CAC 255 0.3 GAT CCC ACA AGT TC-3_amp_#x2032 5_amp_#x2032 -ACA GGC ATA CAC CAC CAC AT-3_amp_#x2032 5_amp_#x2032 -AGG CAG CAT AGT GAG ACC CCC 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220374 12417341 294892 20237 1421 SLC25A20 CAC CAC 256 0.3 CCC ACA AGT TC-3_amp_#x2032 5_amp_#x2032 -ACA GGC ATA CAC CAC CAC AT-3_amp_#x2032 5_amp_#x2032 -AGG CAG CAT AGT GAG ACC CCC ATC 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220375 12417341 294892 8451 13734 GLYAT CAT CAT 260 0.5 -ACA GGC ATA CAC CAC CAC AT-3_amp_#x2032 5_amp_#x2032 -AGG CAG CAT AGT GAG ACC CCC ATC TCT ATA-3_amp_#x2032 clone 10 5_amp_#x2032 11 JUMiner_v2.2 1 2 35 0 1 0 TotalCon:2<>1516|CAT|847|Complete__13734|GLYAT|10249|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 220376 12417341 294892 1271 795 ATM ATC ATC 265 0.5 CAC AT-3_amp_#x2032 5_amp_#x2032 -AGG CAG CAT AGT GAG ACC CCC ATC TCT ATA-3_amp_#x2032 clone 10 5_amp_#x2032 -AGC TGC AGA ACA AGG 11 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220377 12417341 294892 1271 795 ATM ATA ATA-3_amp_#x2032 267 0.5 5_amp_#x2032 -AGG CAG CAT AGT GAG ACC CCC ATC TCT ATA-3_amp_#x2032 clone 10 5_amp_#x2032 -AGC TGC AGA ACA AGG AGC AT-3_amp_#x2032 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220378 12417341 294892 8278 4250 GGT1 GTG GTG 277 0.5 10 5_amp_#x2032 -AGC TGC AGA ACA AGG AGC AT-3_amp_#x2032 5_amp_#x2032 -GTG AAG CCC CAC TTC TTT GA-3_amp_#x2032 5_amp_#x2032 -AGT TCA AGT 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220379 12417341 294892 20237 1421 SLC25A20 CAC CAC 280 0.3 TGC AGA ACA AGG AGC AT-3_amp_#x2032 5_amp_#x2032 -GTG AAG CCC CAC TTC TTT GA-3_amp_#x2032 5_amp_#x2032 -AGT TCA AGT TTC CTG GCC 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220380 12417341 294892 7572 17371 FHL5 ACT ACT 296 0.3 TTC CTG GCC GCC AGA AGA T-3_amp_#x2032 clone 11 5_amp_#x2032 -ACT GGT ACC CGT TGG AAC AA-3_amp_#x2032 5_amp_#x2032 -GTT CAT CCC 1 JUMiner_v2.2 1 2 35 0 2 145 TotalCon:6<>24157|ACOT7|11332|Complete__17371|FHL5|9457|Complete__16|SERPINA3|12|Complete__17780|ACTBL2|345651|No_GeneRif__144|ACTG1|71|Complete__145|ACTG2|72|Complete__<>AvaiableGeneRif=5<>BEST:145|ACTG2|0.000895372811881351<>ScoreDetail__17371|FHL5|0.000809922710232795__145|ACTG2|0.000895372811881351__24157|ACOT7|0.000565426561631495__144|ACTG1|0.000314582224765653__16|SERPINA3|0.000578228402579135__ 0 0 0 0 0 220381 12417341 294892 8278 4250 GGT1 GGT GGT 297 0.5 CTG GCC GCC AGA AGA T-3_amp_#x2032 clone 11 5_amp_#x2032 -ACT GGT ACC CGT TGG AAC AA-3_amp_#x2032 5_amp_#x2032 -GTT CAT CCC ATC 1 JUMiner_v2.2 1 2 35 0 1 0 TotalCon:6<>4250|GGT1|2678|Complete__4251|GGT2|728441|No_GeneRif__33426|GGTLC3|728226|No_GeneRif__33428|GGTLC4P|729838|No_GeneRif__33427|GGTLC5P|653590|No_GeneRif__4252|GGT3P|2679|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 220382 12417341 294892 8451 13734 GLYAT CAT CAT 304 0.5 5_amp_#x2032 -ACT GGT ACC CGT TGG AAC AA-3_amp_#x2032 5_amp_#x2032 -GTT CAT CCC ATC GTG GAT TT-3_amp_#x2032 5_amp_#x2032 -TGG TAC ACG ATT 11 JUMiner_v2.2 1 2 35 0 1 0 TotalCon:2<>1516|CAT|847|Complete__13734|GLYAT|10249|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 220383 12417341 294892 1271 795 ATM ATC ATC 306 0.5 GGT ACC CGT TGG AAC AA-3_amp_#x2032 5_amp_#x2032 -GTT CAT CCC ATC GTG GAT TT-3_amp_#x2032 5_amp_#x2032 -TGG TAC ACG ATT TTT AAG 11 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220384 12417341 294892 8278 4250 GGT1 GTG GTG 307 0.5 ACC CGT TGG AAC AA-3_amp_#x2032 5_amp_#x2032 -GTT CAT CCC ATC GTG GAT TT-3_amp_#x2032 5_amp_#x2032 -TGG TAC ACG ATT TTT AAG GAC 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220385 12417341 294892 8451 13734 GLYAT GAT GAT 308 0.5 CGT TGG AAC AA-3_amp_#x2032 5_amp_#x2032 -GTT CAT CCC ATC GTG GAT TT-3_amp_#x2032 5_amp_#x2032 -TGG TAC ACG ATT TTT AAG GAC CAC 11 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220386 12417341 294892 20237 1421 SLC25A20 CAC CAC 317 0.3 GAT TT-3_amp_#x2032 5_amp_#x2032 -TGG TAC ACG ATT TTT AAG GAC CAC GTG TCT-3_amp_#x2032 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220387 12417341 294892 8278 4250 GGT1 GTG GTG 318 0.5 TT-3_amp_#x2032 5_amp_#x2032 -TGG TAC ACG ATT TTT AAG GAC CAC GTG TCT-3_amp_#x2032 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220388 12417341 294892 8012 4065 GAA GAA GAA 14 0.1 primer reverse primer and TaqMan probe GAPDH 5_amp_#x2032 -CCT GGA GAA ACC TGC CAA GTA T-3_amp_#x2032 5_amp_#x2032 -TGA AGT CGC AGG 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220389 12417341 294892 130 84 ACACA ACC ACC 15 0.0 reverse primer and TaqMan probe GAPDH 5_amp_#x2032 -CCT GGA GAA ACC TGC CAA GTA T-3_amp_#x2032 5_amp_#x2032 -TGA AGT CGC AGG AGA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220390 12417341 294892 22079 11778 TGM2 TGC TGC 16 0.0 primer and TaqMan probe GAPDH 5_amp_#x2032 -CCT GGA GAA ACC TGC CAA GTA T-3_amp_#x2032 5_amp_#x2032 -TGA AGT CGC AGG AGA CAA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220391 12417341 294892 10718 6138 ITGA2B GTA GTA 18 0.0 TaqMan probe GAPDH 5_amp_#x2032 -CCT GGA GAA ACC TGC CAA GTA T-3_amp_#x2032 5_amp_#x2032 -TGA AGT CGC AGG AGA CAA CCT-3_amp_#x2032 5_amp_#x2032 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220392 12417341 294892 21860 11592 TBX1 TGA TGA 20 0.0 5_amp_#x2032 -CCT GGA GAA ACC TGC CAA GTA T-3_amp_#x2032 5_amp_#x2032 -TGA AGT CGC AGG AGA CAA CCT-3_amp_#x2032 5_amp_#x2032 -CAT CAA GAA 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220393 12417341 294892 452 333 AGT AGT AGT 21 0.0 -CCT GGA GAA ACC TGC CAA GTA T-3_amp_#x2032 5_amp_#x2032 -TGA AGT CGC AGG AGA CAA CCT-3_amp_#x2032 5_amp_#x2032 -CAT CAA GAA GGT 1 JUMiner_v2.2 1 0 0 2 341 TotalCon:2<>333|AGT|183|Complete__341|AGXT|189|Complete__<>AvaiableGeneRif=2<>BEST:341|AGXT|0.000452679490518535<>ScoreDetail__333|AGT|0.000350759529288421__341|AGXT|0.000452679490518535__ 0 0 0 0 0 220394 12417341 294892 426 318 AGA AGA AGA 24 0.1 ACC TGC CAA GTA T-3_amp_#x2032 5_amp_#x2032 -TGA AGT CGC AGG AGA CAA CCT-3_amp_#x2032 5_amp_#x2032 -CAT CAA GAA GGT GGT GAA GCA 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220395 12417341 294892 8012 4065 GAA GAA GAA 29 0.4 -TGA AGT CGC AGG AGA CAA CCT-3_amp_#x2032 5_amp_#x2032 -CAT CAA GAA GGT GGT GAA GCA GGC ATC-3_amp_#x2032 clone 1 5_amp_#x2032 -CCG 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220396 12417341 294892 8012 4065 GAA GAA GAA 32 0.3 AGG AGA CAA CCT-3_amp_#x2032 5_amp_#x2032 -CAT CAA GAA GGT GGT GAA GCA GGC ATC-3_amp_#x2032 clone 1 5_amp_#x2032 -CCG TCA CTC AAA 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220397 12417341 294892 8190 15990 GCA GCA GCA 33 0.2 AGA CAA CCT-3_amp_#x2032 5_amp_#x2032 -CAT CAA GAA GGT GGT GAA GCA GGC ATC-3_amp_#x2032 clone 1 5_amp_#x2032 -CCG TCA CTC AAA AGG 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220398 12417341 294892 17 13666 AAAS AAA AAA 41 0.0 GAA GCA GGC ATC-3_amp_#x2032 clone 1 5_amp_#x2032 -CCG TCA CTC AAA AGG TTG AA-3_amp_#x2032 5_amp_#x2032 -TGG CGT GTG AAG TGA CTT 1 JUMiner_v2.2 1 0 0 2 13666 TotalCon:2<>13666|AAAS|8086|Complete__620|APP|351|Complete__<>AvaiableGeneRif=2<>BEST:13666|AAAS|0.000598571450610142<>ScoreDetail__13666|AAAS|0.000598571450610142__620|APP|0.000379773565387191__ 0 0 0 0 0 220399 12417341 294892 23680 12555 UGT8 CGT CGT 46 0.2 5_amp_#x2032 -CCG TCA CTC AAA AGG TTG AA-3_amp_#x2032 5_amp_#x2032 -TGG CGT GTG AAG TGA CTT TT-3_amp_#x2032 5_amp_#x2032 -AGC ATG AAG AGA 5 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220400 12417341 294892 13410 7211 MPG AAG AAG 48 0.2 TCA CTC AAA AGG TTG AA-3_amp_#x2032 5_amp_#x2032 -TGG CGT GTG AAG TGA CTT TT-3_amp_#x2032 5_amp_#x2032 -AGC ATG AAG AGA CCT TTG 5 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220401 12417341 294892 21860 11592 TBX1 TGA TGA 49 0.1 CTC AAA AGG TTG AA-3_amp_#x2032 5_amp_#x2032 -TGG CGT GTG AAG TGA CTT TT-3_amp_#x2032 5_amp_#x2032 -AGC ATG AAG AGA CCT TTG AGG 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220402 12417341 294892 13410 7211 MPG AAG AAG 54 0.1 -TGG CGT GTG AAG TGA CTT TT-3_amp_#x2032 5_amp_#x2032 -AGC ATG AAG AGA CCT TTG AGG AGA AAC TAG TG-3_amp_#x2032 clone 2 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220403 12417341 294892 426 318 AGA AGA AGA 55 0.2 CGT GTG AAG TGA CTT TT-3_amp_#x2032 5_amp_#x2032 -AGC ATG AAG AGA CCT TTG AGG AGA AAC TAG TG-3_amp_#x2032 clone 2 5_amp_#x2032 5 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220404 12417341 294892 426 318 AGA AGA AGA 59 0.0 CTT TT-3_amp_#x2032 5_amp_#x2032 -AGC ATG AAG AGA CCT TTG AGG AGA AAC TAG TG-3_amp_#x2032 clone 2 5_amp_#x2032 -AAG AGC AAG GAC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220405 12417341 294892 13410 7211 MPG AAG AAG 65 0.0 CCT TTG AGG AGA AAC TAG TG-3_amp_#x2032 clone 2 5_amp_#x2032 -AAG AGC AAG GAC CGC AAG TA-3_amp_#x2032 5_amp_#x2032 -GGG TGG CTC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220406 12417341 294892 13410 7211 MPG AAG AAG 67 0.0 AGG AGA AAC TAG TG-3_amp_#x2032 clone 2 5_amp_#x2032 -AAG AGC AAG GAC CGC AAG TA-3_amp_#x2032 5_amp_#x2032 -GGG TGG CTC AGG TGA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220407 12417341 294892 13410 7211 MPG AAG AAG 70 0.0 TAG TG-3_amp_#x2032 clone 2 5_amp_#x2032 -AAG AGC AAG GAC CGC AAG TA-3_amp_#x2032 5_amp_#x2032 -GGG TGG CTC AGG TGA AGT AG-3_amp_#x2032 5_amp_#x2032 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220408 12417341 294892 21860 11592 TBX1 TGA TGA 76 0.0 AAG GAC CGC AAG TA-3_amp_#x2032 5_amp_#x2032 -GGG TGG CTC AGG TGA AGT AG-3_amp_#x2032 5_amp_#x2032 -CTC AGC GAG TAT GGC ATC AAT 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220409 12417341 294892 452 333 AGT AGT AGT 77 0.0 GAC CGC AAG TA-3_amp_#x2032 5_amp_#x2032 -GGG TGG CTC AGG TGA AGT AG-3_amp_#x2032 5_amp_#x2032 -CTC AGC GAG TAT GGC ATC AAT GTG 1 JUMiner_v2.2 1 0 0 2 341 TotalCon:2<>333|AGT|183|Complete__341|AGXT|189|Complete__<>AvaiableGeneRif=2<>BEST:341|AGXT|0.000452679490518535<>ScoreDetail__333|AGT|0.000350759529288421__341|AGXT|0.000452679490518535__ 0 0 0 0 0 220410 12417341 294892 21790 11573 TAT TAT TAT 82 0.1 TGG CTC AGG TGA AGT AG-3_amp_#x2032 5_amp_#x2032 -CTC AGC GAG TAT GGC ATC AAT GTG AAG AAG-3_amp_#x2032 clone 3 5_amp_#x2032 -TAG 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220411 12417341 294892 19697 8941 SERPINA1 AAT AAT 85 0.4 TGA AGT AG-3_amp_#x2032 5_amp_#x2032 -CTC AGC GAG TAT GGC ATC AAT GTG AAG AAG-3_amp_#x2032 clone 3 5_amp_#x2032 -TAG GAG CCA TCC 5 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220412 12417341 294892 13410 7211 MPG AAG AAG 87 0.2 AG-3_amp_#x2032 5_amp_#x2032 -CTC AGC GAG TAT GGC ATC AAT GTG AAG AAG-3_amp_#x2032 clone 3 5_amp_#x2032 -TAG GAG CCA TCC GAG ACA 5 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220413 12417341 294892 13410 7211 MPG AAG AAG-3_amp_#x2032 88 0.1 5_amp_#x2032 -CTC AGC GAG TAT GGC ATC AAT GTG AAG AAG-3_amp_#x2032 clone 3 5_amp_#x2032 -TAG GAG CCA TCC GAG ACA AC-3_amp_#x2032 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220414 12417341 294892 7357 3604 FBN2 CCA CCA 93 0.0 ATC AAT GTG AAG AAG-3_amp_#x2032 clone 3 5_amp_#x2032 -TAG GAG CCA TCC GAG ACA AC-3_amp_#x2032 5_amp_#x2032 -TAC CAT GGC ACT TCC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220415 12417341 294892 21860 11592 TBX1 TGA TGA 103 0.2 TCC GAG ACA AC-3_amp_#x2032 5_amp_#x2032 -TAC CAT GGC ACT TCC TGA CA-3_amp_#x2032 5_amp_#x2032 -CAC TAG CTG GAG CCA GTA TAA CGG 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220416 12417341 294892 7357 3604 FBN2 CCA CCA 109 0.0 GGC ACT TCC TGA CA-3_amp_#x2032 5_amp_#x2032 -CAC TAG CTG GAG CCA GTA TAA CGG GGA-3_amp_#x2032 clone 4 5_amp_#x2032 -GAA GCT GAA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220417 12417341 294892 10718 6138 ITGA2B GTA GTA 110 0.0 ACT TCC TGA CA-3_amp_#x2032 5_amp_#x2032 -CAC TAG CTG GAG CCA GTA TAA CGG GGA-3_amp_#x2032 clone 4 5_amp_#x2032 -GAA GCT GAA GCA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220418 12417341 294892 8012 4065 GAA GAA GAA 116 0.0 CTG GAG CCA GTA TAA CGG GGA-3_amp_#x2032 clone 4 5_amp_#x2032 -GAA GCT GAA GCA GGA TCA AA-3_amp_#x2032 5_amp_#x2032 -AGG GAG CAG 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220419 12417341 294892 17756 9753 QPCT GCT GCT 117 0.0 GAG CCA GTA TAA CGG GGA-3_amp_#x2032 clone 4 5_amp_#x2032 -GAA GCT GAA GCA GGA TCA AA-3_amp_#x2032 5_amp_#x2032 -AGG GAG CAG CTT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220420 12417341 294892 8012 4065 GAA GAA GAA 118 0.0 CCA GTA TAA CGG GGA-3_amp_#x2032 clone 4 5_amp_#x2032 -GAA GCT GAA GCA GGA TCA AA-3_amp_#x2032 5_amp_#x2032 -AGG GAG CAG CTT TCA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220421 12417341 294892 8190 15990 GCA GCA GCA 119 0.0 GTA TAA CGG GGA-3_amp_#x2032 clone 4 5_amp_#x2032 -GAA GCT GAA GCA GGA TCA AA-3_amp_#x2032 5_amp_#x2032 -AGG GAG CAG CTT TCA CCT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220422 12417341 294892 13410 7211 MPG AAG AAG 130 0.1 AA-3_amp_#x2032 5_amp_#x2032 -AGG GAG CAG CTT TCA CCT AT-3_amp_#x2032 5_amp_#x2032 -AAG TCC TTA AGA AAG CTG GGC TTG CCC AC-3_amp_#x2032 clone 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220423 12417341 294892 426 318 AGA AGA AGA 133 0.0 GAG CAG CTT TCA CCT AT-3_amp_#x2032 5_amp_#x2032 -AAG TCC TTA AGA AAG CTG GGC TTG CCC AC-3_amp_#x2032 clone 5 5_amp_#x2032 -GCC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220424 12417341 294892 13410 7211 MPG AAG AAG 134 0.0 CAG CTT TCA CCT AT-3_amp_#x2032 5_amp_#x2032 -AAG TCC TTA AGA AAG CTG GGC TTG CCC AC-3_amp_#x2032 clone 5 5_amp_#x2032 -GCC TGT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220425 12417341 294892 130 84 ACACA ACC ACC 146 0.2 TTG CCC AC-3_amp_#x2032 clone 5 5_amp_#x2032 -GCC TGT TCT GTC ACC ATC AA-3_amp_#x2032 5_amp_#x2032 -GCA GAG GCC ACA GGT TTA GA-3_amp_#x2032 5 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220426 12417341 294892 8190 15990 GCA GCA GCA 149 0.1 5 5_amp_#x2032 -GCC TGT TCT GTC ACC ATC AA-3_amp_#x2032 5_amp_#x2032 -GCA GAG GCC ACA GGT TTA GA-3_amp_#x2032 5_amp_#x2032 -CCA TTC AGC 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220427 12417341 294892 7357 3604 FBN2 CCA CCA 156 0.0 AA-3_amp_#x2032 5_amp_#x2032 -GCA GAG GCC ACA GGT TTA GA-3_amp_#x2032 5_amp_#x2032 -CCA TTC AGC AGT CCA TTG AAA GGC TCT TAG-3_amp_#x2032 clone 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220428 12417341 294892 452 333 AGT AGT AGT 159 0.0 GAG GCC ACA GGT TTA GA-3_amp_#x2032 5_amp_#x2032 -CCA TTC AGC AGT CCA TTG AAA GGC TCT TAG-3_amp_#x2032 clone 6 5_amp_#x2032 -CCT 1 JUMiner_v2.2 1 0 0 2 341 TotalCon:2<>333|AGT|183|Complete__341|AGXT|189|Complete__<>AvaiableGeneRif=2<>BEST:341|AGXT|0.000452679490518535<>ScoreDetail__333|AGT|0.000350759529288421__341|AGXT|0.000452679490518535__ 0 0 0 0 0 220429 12417341 294892 7357 3604 FBN2 CCA CCA 160 0.0 GCC ACA GGT TTA GA-3_amp_#x2032 5_amp_#x2032 -CCA TTC AGC AGT CCA TTG AAA GGC TCT TAG-3_amp_#x2032 clone 6 5_amp_#x2032 -CCT GTT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220430 12417341 294892 17 13666 AAAS AAA AAA 162 0.0 GGT TTA GA-3_amp_#x2032 5_amp_#x2032 -CCA TTC AGC AGT CCA TTG AAA GGC TCT TAG-3_amp_#x2032 clone 6 5_amp_#x2032 -CCT GTT GGA GGA 1 JUMiner_v2.2 1 0 0 2 13666 TotalCon:2<>13666|AAAS|8086|Complete__620|APP|351|Complete__<>AvaiableGeneRif=2<>BEST:13666|AAAS|0.000598571450610142<>ScoreDetail__13666|AAAS|0.000598571450610142__620|APP|0.000379773565387191__ 0 0 0 0 0 220431 12417341 294892 8190 15990 GCA GCA GCA 172 0.0 GGC TCT TAG-3_amp_#x2032 clone 6 5_amp_#x2032 -CCT GTT GGA GGA GCA GAA CT-3_amp_#x2032 5_amp_#x2032 -GAA GCC ACA GAC AGC ACA GA-3_amp_#x2032 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220432 12417341 294892 8012 4065 GAA GAA GAA 173 0.0 TCT TAG-3_amp_#x2032 clone 6 5_amp_#x2032 -CCT GTT GGA GGA GCA GAA CT-3_amp_#x2032 5_amp_#x2032 -GAA GCC ACA GAC AGC ACA GA-3_amp_#x2032 5_amp_#x2032 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220433 12417341 294892 8012 4065 GAA GAA GAA 175 0.0 6 5_amp_#x2032 -CCT GTT GGA GGA GCA GAA CT-3_amp_#x2032 5_amp_#x2032 -GAA GCC ACA GAC AGC ACA GA-3_amp_#x2032 5_amp_#x2032 -AGG GCC CTA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220434 12417341 294892 130 84 ACACA ACC ACC 186 0.2 ACA GAC AGC ACA GA-3_amp_#x2032 5_amp_#x2032 -AGG GCC CTA ACT ACC TGA CGG CCT GT-3_amp_#x2032 clone 7 5_amp_#x2032 -GTT GAC CGA 5 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220435 12417341 294892 21860 11592 TBX1 TGA TGA 187 0.2 GAC AGC ACA GA-3_amp_#x2032 5_amp_#x2032 -AGG GCC CTA ACT ACC TGA CGG CCT GT-3_amp_#x2032 clone 7 5_amp_#x2032 -GTT GAC CGA GCT 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220436 12417341 294892 4265 1885 CGA CGA CGA 195 0.0 ACC TGA CGG CCT GT-3_amp_#x2032 clone 7 5_amp_#x2032 -GTT GAC CGA GCT GGA GAA AG-3_amp_#x2032 5_amp_#x2032 -CCT GTA GAC GGC ATG 1 JUMiner_v2.2 1 0 0 2 1929 TotalCon:2<>1885|CGA|1081|Complete__1929|CHGA|1113|Complete__<>AvaiableGeneRif=2<>BEST:1929|CHGA|0.000418791508538899<>ScoreDetail__1885|CGA|0.00034398566484308__1929|CHGA|0.000418791508538899__ 0 0 0 0 0 220437 12417341 294892 17756 9753 QPCT GCT GCT 196 0.0 TGA CGG CCT GT-3_amp_#x2032 clone 7 5_amp_#x2032 -GTT GAC CGA GCT GGA GAA AG-3_amp_#x2032 5_amp_#x2032 -CCT GTA GAC GGC ATG GAA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220438 12417341 294892 8012 4065 GAA GAA GAA 198 0.1 CCT GT-3_amp_#x2032 clone 7 5_amp_#x2032 -GTT GAC CGA GCT GGA GAA AG-3_amp_#x2032 5_amp_#x2032 -CCT GTA GAC GGC ATG GAA AT-3_amp_#x2032 5_amp_#x2032 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220439 12417341 294892 10718 6138 ITGA2B GTA GTA 201 0.2 5_amp_#x2032 -GTT GAC CGA GCT GGA GAA AG-3_amp_#x2032 5_amp_#x2032 -CCT GTA GAC GGC ATG GAA AT-3_amp_#x2032 5_amp_#x2032 -CAT CGA CGT CTA 5 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220440 12417341 294892 8012 4065 GAA GAA GAA 205 0.1 GCT GGA GAA AG-3_amp_#x2032 5_amp_#x2032 -CCT GTA GAC GGC ATG GAA AT-3_amp_#x2032 5_amp_#x2032 -CAT CGA CGT CTA CCA CAA GTA CTC 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220441 12417341 294892 4265 1885 CGA CGA CGA 208 0.2 5_amp_#x2032 -CCT GTA GAC GGC ATG GAA AT-3_amp_#x2032 5_amp_#x2032 -CAT CGA CGT CTA CCA CAA GTA CTC CCT GAT-3_amp_#x2032 clone 8 5 JUMiner_v2.2 1 2 35 0 2 1929 TotalCon:2<>1885|CGA|1081|Complete__1929|CHGA|1113|Complete__<>AvaiableGeneRif=2<>BEST:1929|CHGA|0.000418791508538899<>ScoreDetail__1885|CGA|0.00034398566484308__1929|CHGA|0.000418791508538899__ 0 0 0 0 0 220442 12417341 294892 23680 12555 UGT8 CGT CGT 209 0.1 -CCT GTA GAC GGC ATG GAA AT-3_amp_#x2032 5_amp_#x2032 -CAT CGA CGT CTA CCA CAA GTA CTC CCT GAT-3_amp_#x2032 clone 8 5_amp_#x2032 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220443 12417341 294892 7357 3604 FBN2 CCA CCA 211 0.0 GAC GGC ATG GAA AT-3_amp_#x2032 5_amp_#x2032 -CAT CGA CGT CTA CCA CAA GTA CTC CCT GAT-3_amp_#x2032 clone 8 5_amp_#x2032 -AAG TGC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220444 12417341 294892 10718 6138 ITGA2B GTA GTA 213 0.1 ATG GAA AT-3_amp_#x2032 5_amp_#x2032 -CAT CGA CGT CTA CCA CAA GTA CTC CCT GAT-3_amp_#x2032 clone 8 5_amp_#x2032 -AAG TGC GAG GGA 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220445 12417341 294892 13410 7211 MPG AAG AAG 219 0.0 CTA CCA CAA GTA CTC CCT GAT-3_amp_#x2032 clone 8 5_amp_#x2032 -AAG TGC GAG GGA TGC AAA T-3_amp_#x2032 5_amp_#x2032 -ACA CAG TCC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220446 12417341 294892 22079 11778 TGM2 TGC TGC 220 0.0 CCA CAA GTA CTC CCT GAT-3_amp_#x2032 clone 8 5_amp_#x2032 -AAG TGC GAG GGA TGC AAA T-3_amp_#x2032 5_amp_#x2032 -ACA CAG TCC TTG 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220447 12417341 294892 22079 11778 TGM2 TGC TGC 223 0.0 CTC CCT GAT-3_amp_#x2032 clone 8 5_amp_#x2032 -AAG TGC GAG GGA TGC AAA T-3_amp_#x2032 5_amp_#x2032 -ACA CAG TCC TTG GCA CAC TT-3_amp_#x2032 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220448 12417341 294892 17 13666 AAAS AAA AAA 224 0.0 CCT GAT-3_amp_#x2032 clone 8 5_amp_#x2032 -AAG TGC GAG GGA TGC AAA T-3_amp_#x2032 5_amp_#x2032 -ACA CAG TCC TTG GCA CAC TT-3_amp_#x2032 5_amp_#x2032 1 JUMiner_v2.2 1 0 0 2 13666 TotalCon:2<>13666|AAAS|8086|Complete__620|APP|351|Complete__<>AvaiableGeneRif=2<>BEST:13666|AAAS|0.000598571450610142<>ScoreDetail__13666|AAAS|0.000598571450610142__620|APP|0.000379773565387191__ 0 0 0 0 0 220449 12417341 294892 8190 15990 GCA GCA GCA 230 0.2 GAG GGA TGC AAA T-3_amp_#x2032 5_amp_#x2032 -ACA CAG TCC TTG GCA CAC TT-3_amp_#x2032 5_amp_#x2032 -ACC TCC TGC AAG AAG AGC TGC 5 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220450 12417341 294892 130 84 ACACA ACC ACC 233 0.1 T-3_amp_#x2032 5_amp_#x2032 -ACA CAG TCC TTG GCA CAC TT-3_amp_#x2032 5_amp_#x2032 -ACC TCC TGC AAG AAG AGC TGC TGC TC-3_amp_#x2032 clone 9 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220451 12417341 294892 22079 11778 TGM2 TGC TGC 235 0.0 -ACA CAG TCC TTG GCA CAC TT-3_amp_#x2032 5_amp_#x2032 -ACC TCC TGC AAG AAG AGC TGC TGC TC-3_amp_#x2032 clone 9 5_amp_#x2032 -TCC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220452 12417341 294892 13410 7211 MPG AAG AAG 236 0.0 CAG TCC TTG GCA CAC TT-3_amp_#x2032 5_amp_#x2032 -ACC TCC TGC AAG AAG AGC TGC TGC TC-3_amp_#x2032 clone 9 5_amp_#x2032 -TCC CTT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220453 12417341 294892 13410 7211 MPG AAG AAG 237 0.0 TCC TTG GCA CAC TT-3_amp_#x2032 5_amp_#x2032 -ACC TCC TGC AAG AAG AGC TGC TGC TC-3_amp_#x2032 clone 9 5_amp_#x2032 -TCC CTT GAT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220454 12417341 294892 22079 11778 TGM2 TGC TGC 239 0.0 GCA CAC TT-3_amp_#x2032 5_amp_#x2032 -ACC TCC TGC AAG AAG AGC TGC TGC TC-3_amp_#x2032 clone 9 5_amp_#x2032 -TCC CTT GAT CCC ACA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220455 12417341 294892 22079 11778 TGM2 TGC TGC 240 0.0 CAC TT-3_amp_#x2032 5_amp_#x2032 -ACC TCC TGC AAG AAG AGC TGC TGC TC-3_amp_#x2032 clone 9 5_amp_#x2032 -TCC CTT GAT CCC ACA AGT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220456 12417341 294892 452 333 AGT AGT AGT 249 0.0 TGC TC-3_amp_#x2032 clone 9 5_amp_#x2032 -TCC CTT GAT CCC ACA AGT TC-3_amp_#x2032 5_amp_#x2032 -ACA GGC ATA CAC CAC CAC AT-3_amp_#x2032 5_amp_#x2032 1 JUMiner_v2.2 1 0 0 2 341 TotalCon:2<>333|AGT|183|Complete__341|AGXT|189|Complete__<>AvaiableGeneRif=2<>BEST:341|AGXT|0.000452679490518535<>ScoreDetail__333|AGT|0.000350759529288421__341|AGXT|0.000452679490518535__ 0 0 0 0 0 220457 12417341 294892 452 333 AGT AGT AGT 261 0.2 GGC ATA CAC CAC CAC AT-3_amp_#x2032 5_amp_#x2032 -AGG CAG CAT AGT GAG ACC CCC ATC TCT ATA-3_amp_#x2032 clone 10 5_amp_#x2032 -AGC 5 JUMiner_v2.2 1 2 35 0 2 341 TotalCon:2<>333|AGT|183|Complete__341|AGXT|189|Complete__<>AvaiableGeneRif=2<>BEST:341|AGXT|0.000452679490518535<>ScoreDetail__333|AGT|0.000350759529288421__341|AGXT|0.000452679490518535__ 0 0 0 0 0 220458 12417341 294892 130 84 ACACA ACC ACC 263 0.1 CAC CAC CAC AT-3_amp_#x2032 5_amp_#x2032 -AGG CAG CAT AGT GAG ACC CCC ATC TCT ATA-3_amp_#x2032 clone 10 5_amp_#x2032 -AGC TGC AGA 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220459 12417341 294892 22079 11778 TGM2 TGC TGC 271 0.0 GAG ACC CCC ATC TCT ATA-3_amp_#x2032 clone 10 5_amp_#x2032 -AGC TGC AGA ACA AGG AGC AT-3_amp_#x2032 5_amp_#x2032 -GTG AAG CCC CAC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220460 12417341 294892 426 318 AGA AGA AGA 272 0.0 ACC CCC ATC TCT ATA-3_amp_#x2032 clone 10 5_amp_#x2032 -AGC TGC AGA ACA AGG AGC AT-3_amp_#x2032 5_amp_#x2032 -GTG AAG CCC CAC TTC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220461 12417341 294892 13410 7211 MPG AAG AAG 278 0.3 5_amp_#x2032 -AGC TGC AGA ACA AGG AGC AT-3_amp_#x2032 5_amp_#x2032 -GTG AAG CCC CAC TTC TTT GA-3_amp_#x2032 5_amp_#x2032 -AGT TCA AGT TTC 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220462 12417341 294892 452 333 AGT AGT AGT 284 0.0 AT-3_amp_#x2032 5_amp_#x2032 -GTG AAG CCC CAC TTC TTT GA-3_amp_#x2032 5_amp_#x2032 -AGT TCA AGT TTC CTG GCC GCC AGA AGA T-3_amp_#x2032 clone 1 JUMiner_v2.2 1 0 0 2 341 TotalCon:2<>333|AGT|183|Complete__341|AGXT|189|Complete__<>AvaiableGeneRif=2<>BEST:341|AGXT|0.000452679490518535<>ScoreDetail__333|AGT|0.000350759529288421__341|AGXT|0.000452679490518535__ 0 0 0 0 0 220463 12417341 294892 452 333 AGT AGT AGT 286 0.0 -GTG AAG CCC CAC TTC TTT GA-3_amp_#x2032 5_amp_#x2032 -AGT TCA AGT TTC CTG GCC GCC AGA AGA T-3_amp_#x2032 clone 11 5_amp_#x2032 1 JUMiner_v2.2 1 0 0 2 341 TotalCon:2<>333|AGT|183|Complete__341|AGXT|189|Complete__<>AvaiableGeneRif=2<>BEST:341|AGXT|0.000452679490518535<>ScoreDetail__333|AGT|0.000350759529288421__341|AGXT|0.000452679490518535__ 0 0 0 0 0 220464 12417341 294892 426 318 AGA AGA AGA 291 0.0 TTT GA-3_amp_#x2032 5_amp_#x2032 -AGT TCA AGT TTC CTG GCC GCC AGA AGA T-3_amp_#x2032 clone 11 5_amp_#x2032 -ACT GGT ACC CGT TGG 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220465 12417341 294892 426 318 AGA AGA AGA 292 0.0 GA-3_amp_#x2032 5_amp_#x2032 -AGT TCA AGT TTC CTG GCC GCC AGA AGA T-3_amp_#x2032 clone 11 5_amp_#x2032 -ACT GGT ACC CGT TGG AAC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220466 12417341 294892 130 84 ACACA ACC ACC 298 0.3 GCC GCC AGA AGA T-3_amp_#x2032 clone 11 5_amp_#x2032 -ACT GGT ACC CGT TGG AAC AA-3_amp_#x2032 5_amp_#x2032 -GTT CAT CCC ATC GTG 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220467 12417341 294892 23680 12555 UGT8 CGT CGT 299 0.1 GCC AGA AGA T-3_amp_#x2032 clone 11 5_amp_#x2032 -ACT GGT ACC CGT TGG AAC AA-3_amp_#x2032 5_amp_#x2032 -GTT CAT CCC ATC GTG GAT 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220468 12417341 294892 6069 23483 DOCK11 ACG ACG 312 0.0 -GTT CAT CCC ATC GTG GAT TT-3_amp_#x2032 5_amp_#x2032 -TGG TAC ACG ATT TTT AAG GAC CAC GTG TCT-3_amp_#x2032 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220469 12417341 294892 13410 7211 MPG AAG AAG 315 0.1 ATC GTG GAT TT-3_amp_#x2032 5_amp_#x2032 -TGG TAC ACG ATT TTT AAG GAC CAC GTG TCT-3_amp_#x2032 6 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 220470 12417341 294922 21707 11543 TAF10 TAFII30 TAFII30 21 2.1 identical to four known cDNAs 30-kDa TATA-binding protein-associated factor (TAFII30), TAFII30 macrophage-inhibiting factor-related protein-8 (MRP8), MRP8 metallothionein-3 (MT-3) MT-3 and ubiquitin-like 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220471 12417341 294922 19300 10498 S100A8 MRP8 MRP8 25 1.3 30-kDa TATA-binding protein-associated factor (TAFII30), TAFII30 macrophage-inhibiting factor-related protein-8 (MRP8), MRP8 metallothionein-3 (MT-3) MT-3 and ubiquitin-like protein 5 (UBL5), UBL5 respectively 1 JUMiner_v2.2 1 0 0 2 14639 TotalCon:3<>59|ABCC8|6833|Complete__14639|ABCC11|85320|Complete__10498|S100A8|6279|Complete__<>AvaiableGeneRif=3<>BEST:14639|ABCC11|0.000533043602456591<>ScoreDetail__14639|ABCC11|0.000533043602456591__59|ABCC8|0.000440989860179696__10498|S100A8|0.000434574912753281__ 0 0 0 0 0 220472 12417341 294922 13784 7408 MT3 MT3 MT-3 27 1.3 factor (TAFII30), TAFII30 macrophage-inhibiting factor-related protein-8 (MRP8), MRP8 metallothionein-3 (MT-3) MT-3 and ubiquitin-like protein 5 (UBL5), UBL5 respectively 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220473 12417341 294922 16630 8988 PIN1 UBL5 UBL5 32 1.0 (MRP8), MRP8 metallothionein-3 (MT-3) MT-3 and ubiquitin-like protein 5 (UBL5), UBL5 respectively 1 JUMiner_v2.2 1 0 0 2 8988 TotalCon:2<>13736|UBL5|59286|Complete__8988|PIN1|5300|Complete__<>AvaiableGeneRif=2<>BEST:8988|PIN1|0.000423362672004655<>ScoreDetail__13736|UBL5|0.000263546278726544__8988|PIN1|0.000423362672004655__ 0 0 0 0 0 220474 12417341 294924 641 451 AMACR RACE RACE 7 1.3 We cloned these two unknown genes using RACE methods and named them dorfin and neugrin in previous reports 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 220475 12417341 294924 18435 13432 RNF19A dorfin dorfin 12 2.4 these two unknown genes using RACE methods and named them dorfin and neugrin in previous reports 11 and 12 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220476 12417341 294925 21707 11543 TAF10 TAFII30 TAFII30 0 2.1 TAFII30 is one of the TATA-binding protein-associated factors required for transcription 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220477 12417341 294926 1412 10560 ATXN7 SCA7 SCA7 4 1.0 An immunohistochemical study using SCA7 transgenic mice showed that TAFII30 is accumulated in nuclear inclusions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220478 12417341 294926 21707 11543 TAF10 TAFII30 TAFII30 9 2.1 An immunohistochemical study using SCA7 transgenic mice showed that TAFII30 is accumulated in nuclear inclusions in neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220479 12417341 294927 1412 10560 ATXN7 SCA7 SCA7 23 1.0 activity of cellular transcription and contribute to neuronal toxicity in SCA7 model mice 14 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220480 12417341 294928 21707 11543 TAF10 TAFII30 TAFII30 6 2.1 Our result showed up-regulation of the TAFII30 gene in the SALS spinal cords which suggests that this 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220481 12417341 294930 18435 13432 RNF19A DORFIN Dorfin 0 2.4 Dorfin is a new RING finger-type ubiquitin ligase containing two RING 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220482 12417341 294932 18435 13432 RNF19A dorfin dorfin 5 2.4 Our recent study showed that dorfin is localized in the ubiquitinated inclusions of FALS and SALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220483 12417341 294932 20996 11179 SOD1 SOD1 SOD1 23 3.9 FALS and SALS bound and ubiquitinated various mutant forms of SOD1 in vitro and protected from mutant SOD1-mediated neurotoxicity in mutant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220484 12417341 294932 20996 11179 SOD1 SOD1 SOD1-mediated 30 3.9 mutant forms of SOD1 in vitro and protected from mutant SOD1-mediated neurotoxicity in mutant SOD1 culture cells 15 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220485 12417341 294932 20996 11179 SOD1 SOD1 SOD1 34 3.9 in vitro and protected from mutant SOD1-mediated neurotoxicity in mutant SOD1 culture cells 15 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220486 12417341 294933 18435 13432 RNF19A dorfin dorfin 4 2.4 These results indicate that dorfin has a crucial role in the pathomechanism of mutant SOD1-mediated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220487 12417341 294933 20996 11179 SOD1 SOD1 SOD1-mediated 14 3.9 dorfin has a crucial role in the pathomechanism of mutant SOD1-mediated FALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220488 12417341 294934 18435 13432 RNF19A dorfin dorfin 11 2.4 the present study we showed that the expression of the dorfin gene was significantly higher in the SALS than in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220489 12417341 294935 18435 13432 RNF19A dorfin dorfin 16 2.4 function in FALS and is localized in inclusions of SALS dorfin may play some protective role in the pathogenesis of SALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220490 12417341 294936 20996 11179 SOD1 ALS ALS 28 3.9 Huntington disease Alzheimer disease Parkinson disease familial spinocerebellar degeneration and ALS 16 dorfin may possibly work to eliminate proteins which are 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0012197662335473<>ScoreDetail__5468|IGFALS|0.000411226482985504__11179|SOD1|0.0012197662335473__ 0 0 0 0 0 220491 12417341 294936 18435 13432 RNF19A dorfin dorfin 32 2.4 Alzheimer disease Parkinson disease familial spinocerebellar degeneration and ALS 16 dorfin may possibly work to eliminate proteins which are toxic to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220492 12417341 294941 19300 10498 S100A8 MRP8 MRP8 0 1.3 MRP8 is mainly expressed in microglial cells in neuronal tissues and 1 JUMiner_v2.2 1 0 0 2 14639 TotalCon:3<>59|ABCC8|6833|Complete__14639|ABCC11|85320|Complete__10498|S100A8|6279|Complete__<>AvaiableGeneRif=3<>BEST:14639|ABCC11|0.000533043602456591<>ScoreDetail__14639|ABCC11|0.000533043602456591__59|ABCC8|0.000440989860179696__10498|S100A8|0.000434574912753281__ 0 0 0 0 0 220493 12417341 294942 19300 10498 S100A8 MRP8 MRP8 0 1.3 MRP8 decreased in the SALS spinal cords in the present study 1 JUMiner_v2.2 1 0 0 2 14639 TotalCon:3<>59|ABCC8|6833|Complete__14639|ABCC11|85320|Complete__10498|S100A8|6279|Complete__<>AvaiableGeneRif=3<>BEST:14639|ABCC11|0.000533043602456591<>ScoreDetail__14639|ABCC11|0.000533043602456591__59|ABCC8|0.000440989860179696__10498|S100A8|0.000434574912753281__ 0 0 0 0 0 220494 12417341 294943 20996 11179 SOD1 ALS ALS 11 3.9 is paradoxical because gliosis is one of the hallmarks in ALS pathology 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0012197662335473<>ScoreDetail__5468|IGFALS|0.000411226482985504__11179|SOD1|0.0012197662335473__ 0 0 0 0 0 220495 12417341 294945 13784 7408 MT3 MT3 MT-3 0 1.3 MT-3 is a neuron-specific member of the zinc- and copper-binding metallothionein 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220496 12417341 294946 13784 7408 MT3 MT3 MT-3 3 1.3 The elevation of MT-3 expression in G93A SOD1 transgenic mice was reported 21 and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220497 12417341 294946 20996 11179 SOD1 SOD1 SOD1 7 3.9 The elevation of MT-3 expression in G93A SOD1 transgenic mice was reported 21 and 22 and reduction of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220498 12417341 294946 13784 7408 MT3 MT3 MT-3 20 1.3 transgenic mice was reported 21 and 22 and reduction of MT-3 promotes the onset of disease and death in G93A SOD1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220499 12417341 294946 20996 11179 SOD1 SOD1 SOD1 30 3.9 MT-3 promotes the onset of disease and death in G93A SOD1 transgenic mice 23 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220500 12417341 294947 13784 7408 MT3 MT3 MT-3 5 1.3 In sporadic Alzheimer_amp_#x2019 s disease brains MT-3 is significantly down-regulated 19 and 24 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220501 12417341 294948 13784 7408 MT3 MT3 MT-3 7 1.3 In the present study we demonstrated that MT-3 mRNA is decreased in the SALS spinal cords but another 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220502 12417341 294948 13784 7408 MT3 MT3 MT-3 27 1.3 another report failed to show a significant difference in the MT-3 mRNA expression level in SALS 25 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220503 12417341 294949 13784 7408 MT3 MT3 MT-3 3 1.3 The fact that MT-3 was up-regulated in FALS but down-regulated in SALS leads one 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 220504 12417341 294951 16630 8988 PIN1 UBL5 UBL5 0 1.0 UBL5 is one of the ubiquitin-like proteins 1 JUMiner_v2.2 1 0 0 2 8988 TotalCon:2<>13736|UBL5|59286|Complete__8988|PIN1|5300|Complete__<>AvaiableGeneRif=2<>BEST:8988|PIN1|0.000423362672004655<>ScoreDetail__13736|UBL5|0.000263546278726544__8988|PIN1|0.000423362672004655__ 0 0 0 0 0 220505 12417341 294956 20996 11179 SOD1 ALS ALS 26 3.9 and if they are key molecules to explore treatments for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0012197662335473<>ScoreDetail__5468|IGFALS|0.000411226482985504__11179|SOD1|0.0012197662335473__ 0 0 0 0 0 220506 12417341 294964 8118 4141 GAPDH GAPDH GAPDH 14 1.9 shown as the weight ratio of the target gene to GAPDH 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 215952 12528305 289111 20996 11179 SOD1 ALS ALS 3 1.2 Amyotrophic lateral sclerosis (ALS) ALS is a rapidly progressive neuromuscular disease that destroys both upper 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00140420620671967<>ScoreDetail__5468|IGFALS|0.000182481751824818__11179|SOD1|0.00140420620671967__ 0 0 0 0 0 215953 12528305 289112 20996 11179 SOD1 ALS ALS 10 1.2 It is presumed that in the vast majority of cases ALS is acquired and occurs sporadically although the exact etiology is 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00140420620671967<>ScoreDetail__5468|IGFALS|0.000182481751824818__11179|SOD1|0.00140420620671967__ 0 0 0 0 0 199188 12843244 266717 20996 11179 SOD1 SOD1 SOD1 18 5.5 upregulated in the spinal cord of superoxide dismutase 1 (SOD1) SOD1 G93A transgenic mice a mouse model of amyotrophic lateral sclerosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199189 12843244 266717 20996 11179 SOD1 ALS ALS 29 3.2 transgenic mice a mouse model of amyotrophic lateral sclerosis (ALS), ALS before the onset of motor dysfunction and remains at the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199190 12843244 266718 20996 11179 SOD1 SOD1 SOD1 23 5.5 in the spinal cord of symptomatic caspase-11 -/-;SOD1 - - SOD1 G93A mice compared with that of caspase-11 +/-; - SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199191 12843244 266718 20996 11179 SOD1 SOD1 SOD1 32 5.5 SOD1 G93A mice compared with that of caspase-11 +/-; - SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199192 12843244 266719 20996 11179 SOD1 SOD1 SOD1 11 5.5 neurodegeneration inflammatory responses and the disease onset and progression in SOD1 G93A transgenic mice were not altered by the ablation of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199193 12843244 266720 20996 11179 SOD1 ALS ALS 15 3.2 to certain aspects of pathology in this mouse model of ALS their inhibition is not sufficient to prevent neurodegeneration 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199194 12843244 266722 20996 11179 SOD1 ALS ALS 2 3.2 Key words ALS motor neuron degeneration neurodegeneration SOD1 caspase apoptosis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199195 12843244 266722 20996 11179 SOD1 SOD1 SOD1 7 5.5 Key words ALS motor neuron degeneration neurodegeneration SOD1 caspase apoptosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199196 12843244 266723 20996 11179 SOD1 ALS ALS 3 3.2 Amyotrophic lateral sclerosis (ALS) ALS is a fatal neurological disorder characterized by selective degeneration of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199197 12843244 266723 20996 11179 SOD1 SOD1 SOD1 53 5.5 several mutations in the Cu /Zn Zn superoxide dismutase (SOD1) SOD1 are causally responsible for a subset of familial ALS (FALS) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199198 12843244 266723 20996 11179 SOD1 ALS ALS 62 3.2 (SOD1) SOD1 are causally responsible for a subset of familial ALS (FALS) FALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199199 12843244 266724 20996 11179 SOD1 SOD1 SOD1 6 5.5 Consistent with a causal role of SOD1 mutations in FALS transgenic mice expressing human SOD1 mutants develop 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199200 12843244 266724 20996 11179 SOD1 SOD1 SOD1 14 5.5 role of SOD1 mutations in FALS transgenic mice expressing human SOD1 mutants develop age-dependent progressive motor neuron degeneration with cellular pathological 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199201 12843244 266724 20996 11179 SOD1 ALS ALS 31 3.2 degeneration with cellular pathological features similar to that of human ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199202 12843244 266725 20996 11179 SOD1 ALS ALS 14 3.2 apoptosis as a possible mechanism for motor neuron degeneration in ALS (Friedlander Friedlander et al. 1997 Kostic et al. 1997 Li 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199203 12843244 266727 20996 11179 SOD1 SOD1 SOD1 11 5.5 of caspase-1 and caspase-3 in the spinal cords of mutant SOD1 mice and ALS patients has been reported previously (Martin, Martin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199204 12843244 266727 20996 11179 SOD1 ALS ALS 14 3.2 caspase-3 in the spinal cords of mutant SOD1 mice and ALS patients has been reported previously (Martin, Martin 1999 Li et 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199205 12843244 266729 20996 11179 SOD1 SOD1 SOD1 26 5.5 the onset and progression of the disease symptoms in G93A SOD1 (G93A) G93A transgenic mice (Friedlander Friedlander et al. 1997 Li 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199206 12843244 266729 20996 11179 SOD1 ALS ALS 48 3.2 al. 2000 suggesting the importance of caspase-mediated apoptosis in the ALS pathology 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199207 12843244 266730 20996 11179 SOD1 ALS ALS 12 3.2 involvement of both caspase-1 and caspase-3 in the pathogenesis of ALS strongly suggested the involvement of caspase-11 in this process because 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199208 12843244 266730 10437 5992 IL1B IL-1 IL-1 42 1.3 under pathological conditions (Wang Wang et al. 1998 beta (IL-1 IL-1 beta maturation and resistant to lipopolysaccharide (LPS)-induced LPS -induced septic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199209 12843244 266730 24053 12728 VWS LPS LPS 49 0.0 beta (IL-1 IL-1 beta maturation and resistant to lipopolysaccharide (LPS)-induced LPS -induced septic shock (Wang Wang et al. 1998 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 199210 12843244 266731 24053 12728 VWS LPS LPS 5 0.0 Apoptosis and caspase-3 activation by LPS shock or ischemic brain injury are also defective in caspase-11 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 199211 12843244 266733 20996 11179 SOD1 ALS ALS 20 3.2 beneficial effect of general caspase inhibition in mouse models of ALS a critical role of individual caspases in mutant SOD1-mediated neurodegeneration 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199212 12843244 266733 20996 11179 SOD1 SOD1 SOD1-mediated 29 3.2 of ALS a critical role of individual caspases in mutant SOD1-mediated neurodegeneration has not been examined in different caspase mutant mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199213 12843244 266734 20996 11179 SOD1 ALS ALS 23 3.2 resulting apoptosis play an indispensable role in mediating neurodegeneration in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199214 12843244 266735 20996 11179 SOD1 SOD1 SOD1 16 5.5 in relation to the early events of pathogenesis in mutant SOD1 transgenic mice such as mitochondrial dilation neurofilament abnormality and glutamate 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199215 12843244 266740 20996 11179 SOD1 SOD1 SOD1 4 5.5 Mouse lines expressing human SOD1 mutant G93A [C57BL/6J-TgN(SOD1-G93A)1Gurdl] C57BL 6J-TgN SOD1-G93A 1Gurdl were obtained from 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199216 12843244 266742 20996 11179 SOD1 SOD1 SOD1 8 5.5 To minimize the variations in genetic background one SOD1 G93A transgenic male mouse was mated with one female caspase-11 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199217 12843244 266743 20996 11179 SOD1 SOD1 SOD1 4 5.5 An F1 male mouse (caspase-11+/-;SOD1 caspase-11 - SOD1 G93A was mated with two caspase-11 - -mice and one 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199218 12843244 266749 19573 10691 SDS SDS SDS 34 0.0 buffer (150 150 m M NaCl 1% Triton X-100 0.1% SDS and 1% sodium deoxycholate in 50 m M Tris-HCl pH 1 JUMiner_v2.2 1 0 0 2 10691 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:10691|SDS|0.000327439423706614<>ScoreDetail__10691|SDS|0.000327439423706614__19440|SBDS|0.000304380309361078__ 0 0 0 0 0 199219 12843244 266751 20996 11179 SOD1 SOD1 SOD1 5 5.5 Antibodies against human- and mouse-specific SOD1 were obtained from Chemicon (Temecula, Temecula CA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199220 12843244 266765 20996 11179 SOD1 ALS ALS 31 3.2 the disease onset and progression of this mouse model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199221 12843244 266767 20996 11179 SOD1 ALS ALS 33 3.2 is not crucial for neurodegeneration in this mouse model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199222 12843244 266768 10437 5992 IL1B IL-1 IL-1 9 1.3 Furthermore because caspase-11 plays a key role in regulating IL-1 beta maturation in LPS-stimulated mice (Wang Wang et al. 1998 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199223 12843244 266768 24053 12728 VWS LPS LPS-stimulated 13 0.0 plays a key role in regulating IL-1 beta maturation in LPS-stimulated mice (Wang Wang et al. 1998 beta is not a 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 199224 12843244 266769 20996 11179 SOD1 SOD1 SOD1 16 5.5 demonstrating that the neural degeneration and accelerated death of G37R SOD1 mice are not altered in the background of IL-1 beta- 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199225 12843244 266769 10437 5992 IL1B IL-1 IL-1 25 1.3 G37R SOD1 mice are not altered in the background of IL-1 beta- -mice (Nguyen Nguyen et al. 2001 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199226 12843244 266770 20996 11179 SOD1 ALS ALS 21 3.2 targets for the treatment of chronic neurodegenerative diseases such as ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199227 12843244 266771 24053 12728 VWS LPS LPS-induced 15 0.0 been found to be induced under multiple pathological conditions including LPS-induced septic shock (Wang Wang et al. 1996 the experimental autoimmune 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 199228 12843244 266772 24053 12728 VWS LPS LPS-induced 16 0.0 in this paper caspase-11 - -mice were highly resistant to LPS-induced apoptosis and lethality (Wang Wang et al. 1998 Kang et 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 199229 12843244 266773 20996 11179 SOD1 SOD1 SOD1 8 5.5 These results suggest that the expression of G93A SOD1 may induce neurodegeneration through multiple pathways that may involve multiple 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199230 12843244 266774 10437 5992 IL1B IL-1 IL-1 108 1.3 in the absence of caspase-11 Because the complete elimination of IL-1 beta in IL-1 beta- -mice did not alter the disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199231 12843244 266774 10437 5992 IL1B IL-1 IL-1 111 1.3 of caspase-11 Because the complete elimination of IL-1 beta in IL-1 beta- -mice did not alter the disease course of SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199232 12843244 266774 20996 11179 SOD1 SOD1 SOD1 121 5.5 IL-1 beta- -mice did not alter the disease course of SOD1 G37R mice (Nguyen Nguyen et al. 2001 the most likely 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199233 12843244 266774 24053 12728 VWS LPS LPS-induced 9 0.0 and/or and or localized inflammation is a prominent feature of LPS-induced septic shock (Raetz Raetz and Whitfield 2002 beta were significantly 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 199234 12843244 266774 24053 12728 VWS LPS LPS 31 0.0 caspase-11 - -mice compared with wild type when induced with LPS injection or EAE (Wang Wang et al. 1998 epsilon T 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 199235 12843244 266776 20996 11179 SOD1 SOD1 SOD1 4 5.5 Motor neurons expressing mutant SOD1 have been shown to have an enhanced sensitivity toward Fas-induced 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199236 12843244 266776 7333 11920 FAS FAS Fas 27 0.3 (Raoul Raoul et al. 2002 although the critical role of Fas pathway in mediating motor neuron degeneration has not been evaluated 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000586211078911917<>ScoreDetail__11920|FAS|0.000586211078911917__3594|FASN|0.000477932228857231__ 0 0 0 0 0 199237 12843244 266777 3532 1509 CASP8 caspase-8 caspase-8 11 2.0 this regard it is worth noting that the activation of caspase-8 and -9 was found only at the end stage of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199238 12843244 266777 20996 11179 SOD1 SOD SOD-expressing 23 3.2 -9 was found only at the end stage of mutant SOD-expressing transgenic mice (Gu_amp_eacute;gan Gu_amp_eacute gan et al. 2001 2002 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199239 12843244 266779 20996 11179 SOD1 ALS ALS 6 3.2 It has been well documented that ALS motor neurons undergo vacuolarization of the rough endoplasmic reticulum and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199240 12843244 266782 1576 990 BCL2 Bcl-2 Bcl-2 5 1.0 However the weak protection by Bcl-2 overexpression in a mouse model of ALS (Kostic Kostic et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199241 12843244 266782 20996 11179 SOD1 ALS ALS 12 3.2 weak protection by Bcl-2 overexpression in a mouse model of ALS (Kostic Kostic et al. 1997 suggests an involvement of alternative 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199242 12843244 266789 20996 11179 SOD1 SOD1 SOD1 4 5.5 The exact parallels between SOD1 mutant transgenic mice and human ALS are not clear because 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199243 12843244 266789 20996 11179 SOD1 ALS ALS 10 3.2 The exact parallels between SOD1 mutant transgenic mice and human ALS are not clear because of the difference in the temporal 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199244 12843244 266790 20996 11179 SOD1 ALS ALS 12 3.2 activation of caspases and apoptosis in this mouse model of ALS may reflect a secondary degenerative response it remains to be 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199245 12843244 266790 20996 11179 SOD1 ALS ALS 35 3.2 inhibition of selective caspases may be beneficial for treatment of ALS in human 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199246 12843244 266791 20996 11179 SOD1 ALS ALS 8 3.2 In particular considering that onset and progression of ALS in humans occur over a much longer period of time 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199247 12843244 266792 20996 11179 SOD1 ALS ALS 18 3.2 considering caspases as a direct therapeutic target for treatment of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014804281480155<>ScoreDetail__5468|IGFALS|0.00041031399818598__11179|SOD1|0.0014804281480155__ 0 0 0 0 0 199248 12843244 266801 536 387 AKR1C4 C11 C11 18 0.0 cord lysates were prepared from caspase-11+/-; caspase-11 - G93A (C11+/-G93A), C11 -G93A caspase-11-/-; caspase-11- - G93A (C11-/-G93A), C11- -G93A and caspase-11 1 JUMiner_v2.2 1 0 0 2 387 TotalCon:2<>387|AKR1C4|1109|Complete__14121|POLR3K|51728|Complete__<>AvaiableGeneRif=2<>BEST:387|AKR1C4|0.000418929850918756<>ScoreDetail__14121|POLR3K|0.000417485265225933__387|AKR1C4|0.000418929850918756__ 0 0 0 0 0 199249 12843244 266801 536 387 AKR1C4 C11 C11- 21 0.0 - G93A (C11+/-G93A), C11 -G93A caspase-11-/-; caspase-11- - G93A (C11-/-G93A), C11- -G93A and caspase-11 - C11 - mice 1 JUMiner_v2.2 1 0 0 2 387 TotalCon:2<>387|AKR1C4|1109|Complete__14121|POLR3K|51728|Complete__<>AvaiableGeneRif=2<>BEST:387|AKR1C4|0.000418929850918756<>ScoreDetail__14121|POLR3K|0.000417485265225933__387|AKR1C4|0.000418929850918756__ 0 0 0 0 0 199250 12843244 266801 536 387 AKR1C4 C11 C11 23 0.0 caspase-11-/-; caspase-11- - G93A (C11-/-G93A), C11- -G93A and caspase-11 - C11 - mice 1 JUMiner_v2.2 1 0 0 2 387 TotalCon:2<>387|AKR1C4|1109|Complete__14121|POLR3K|51728|Complete__<>AvaiableGeneRif=2<>BEST:387|AKR1C4|0.000418929850918756<>ScoreDetail__14121|POLR3K|0.000417485265225933__387|AKR1C4|0.000418929850918756__ 0 0 0 0 0 199251 12843244 266803 10437 5992 IL1B IL-1 IL-1 4 1.3 C Reduction of IL-1 beta level in the absence of caspase-11 in the caspase-11-/-; 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199252 12843244 266804 10437 5992 IL1B IL-1 IL-1 18 1.3 at indicated days of age and the level of mature IL-1 beta was measured by ELISA ( n = 4 mean_amp_#177 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199253 12843244 266805 20996 11179 SOD1 SOD1 SOD1 8 5.5 D The expression of the human mutant SOD1 protein is not affected by the absence of caspase-11 in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199254 12843244 266806 20996 11179 SOD1 SOD1 SOD1 29 5.5 mouse-specific anti-SOD1 antibodies for the detection of introduced and endogenous SOD1 proteins respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199255 12843244 266833 10437 5992 IL1B IL-1 IL-1 5 1.3 The secretion and maturation of IL-1 beta is another downstream indicator of caspase-11-caspase-1 pathway (Kuida Kuida 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199256 12843244 266834 10437 5992 IL1B IL-1 IL-1 3 1.3 The increase in IL-1 beta levels was first detected at approximately day 90 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199257 12843244 266835 10437 5992 IL1B IL-1 IL-1 3 1.3 The levels of IL-1 beta in the spinal cords of caspase-11 -/-; - - 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199258 12843244 266836 10437 5992 IL1B IL-1 IL-1 12 1.3 indicates that caspase-11 also plays a key role in regulating IL-1 beta levels in the G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199259 12843244 266837 20996 11179 SOD1 SOD1 SOD1 16 5.5 caspase-11 gene affected the expression level of the human mutant SOD1 protein in the double-mutant mice we compared the levels of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199260 12843244 266838 20996 11179 SOD1 SOD1 SOD1 19 5.5 of caspase-11 did not alter the expression of the mutant SOD1 protein in the double-mutant mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199261 12843244 266839 10437 5992 IL1B IL-1 IL-1 20 1.3 the activities of its downstream caspases-1 and -3 and also IL-1 beta levels during the pathogenesis of this model of FALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199262 12843244 266843 8254 4235 GFAP GFAP GFAP 13 2.5 compared the numbers of microglia and astrocytes using MacI and GFAP as their respective markers in the spinal cords of caspase-11 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199263 12843244 266844 8254 4235 GFAP GFAP GFAP-positive 23 2.5 showed dramatic increases in the number of MacI-positive microglia and GFAP-positive astrocytes with no significant differences in the absence or presence 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199264 12843244 266845 10437 5992 IL1B IL-1 IL-1 12 1.3 suggests that despite the significant reduction of caspase activation and IL-1 beta levels in caspase-11 -/-; - - G93A mice the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 199265 12843244 266845 20996 11179 SOD1 SOD1 SOD1 26 5.5 - - G93A mice the inflammatory response induced by mutant SOD1 was not significantly altered 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193298 14511332 258335 17610 9605 PTGS2 COX COX 10 2.2 are produced by two different isoforms of the cyclooxygenase (COX) COX enzyme namely COX-1 and COX-2 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193299 14511332 258335 17609 9604 PTGS1 COX-1 COX-1 13 5.4 two different isoforms of the cyclooxygenase (COX) COX enzyme namely COX-1 and COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193300 14511332 258335 17610 9605 PTGS2 COX-2 COX-2 13 13.4 two different isoforms of the cyclooxygenase (COX) COX enzyme namely COX-1 and COX-2 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193301 14511332 258335 17610 9605 PTGS2 COX-2 COX-2 15 13.4 isoforms of the cyclooxygenase (COX) COX enzyme namely COX-1 and COX-2 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193302 14511332 258336 17610 9605 PTGS2 COX-2 COX-2 2 13.4 In particular COX-2 was demonstrated to be crucial for PG-synthesis in inflammation 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193303 14511332 258337 17610 9605 PTGS2 COX-2 COX-2 3 13.4 Recently inhibition of COX-2 was shown to prevent the loss of motor neurons in 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193304 14511332 258337 20996 11179 SOD1 ALS ALS 20 3.2 motor neurons in a model of amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193305 14511332 258338 17610 9605 PTGS2 COX-2 COX-2 2 13.4 Furthermore spinal COX-2 expression was shown to be increased in transgenic mice that 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193306 14511332 258338 20996 11179 SOD1 ALS ALS-like 15 2.9 shown to be increased in transgenic mice that produce an ALS-like syndrome 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193307 14511332 258339 17609 9604 PTGS1 COX-1 COX-1 6 5.4 Therefore we investigated the expression of COX-1 and COX-2 in the spinal cord of seven human sporadic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193308 14511332 258339 17610 9605 PTGS2 COX-2 COX-2 6 13.4 Therefore we investigated the expression of COX-1 and COX-2 in the spinal cord of seven human sporadic 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193309 14511332 258339 17610 9605 PTGS2 COX-2 COX-2 8 13.4 Therefore we investigated the expression of COX-1 and COX-2 in the spinal cord of seven human sporadic ALS patients 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193310 14511332 258339 20996 11179 SOD1 ALS ALS 17 3.2 and COX-2 in the spinal cord of seven human sporadic ALS patients by means of immunohistochemistry 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193311 14511332 258341 17610 9605 PTGS2 COX-2 COX-2 0 13.4 COX-2 expression was dramatically increased in the spinal cord of patients 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193312 14511332 258341 20996 11179 SOD1 ALS ALS 12 3.2 was dramatically increased in the spinal cord of patients with ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193313 14511332 258343 17610 9605 PTGS2 COX-2 COX-2 8 13.4 Statistical analysis showed a significantly higher expression of COX-2 in ALS for both neurons and glia 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193314 14511332 258343 20996 11179 SOD1 ALS ALS 10 3.2 Statistical analysis showed a significantly higher expression of COX-2 in ALS for both neurons and glia 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193315 14511332 258344 17609 9604 PTGS1 COX-1 COX-1 2 5.4 In contrast COX-1 expression was predominantly confined to microglia and no apparent difference 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193316 14511332 258344 20996 11179 SOD1 ALS ALS 18 3.2 microglia and no apparent difference was detected between controls and ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193317 14511332 258345 17610 9605 PTGS2 COX COX 17 2.2 prostaglandin E2 (PG PG E 2 as a marker for COX activity in the cerebrospinal fluid of nine patients diagnosed for 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193318 14511332 258345 20996 11179 SOD1 ALS ALS 28 3.2 activity in the cerebrospinal fluid of nine patients diagnosed for ALS and compared the results with those from nine patients without 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193319 14511332 258346 20996 11179 SOD1 ALS ALS 8 3.2 PG E 2 levels were markedly increased in ALS cases (45.8 45.8 _amp_plusmn 35.1 pg/mL) pg mL compared to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193320 14511332 258347 17610 9605 PTGS2 COX-2 COX-2 10 13.4 The results of our study corroborate a potential role for COX-2 in the pathogenesis of motor neuron death in ALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193321 14511332 258347 20996 11179 SOD1 ALS ALS 19 3.2 for COX-2 in the pathogenesis of motor neuron death in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193322 14511332 258348 17610 9605 PTGS2 COX-2 COX-2 1 13.4 Selective COX-2 inhibition might therefore offer a new possibility in the treatment 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193323 14511332 258348 20996 11179 SOD1 ALS ALS 14 3.2 therefore offer a new possibility in the treatment of human ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193324 14511332 258349 17610 9605 PTGS2 COX-2 COX-2 7 13.4 However to determine the exact role of COX-2 in human ALS will require further research 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193325 14511332 258349 20996 11179 SOD1 ALS ALS 10 3.2 However to determine the exact role of COX-2 in human ALS will require further research 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193326 14511332 258352 20996 11179 SOD1 SOD1 SOD1 11 2.9 gene encoding for the Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 account for a familial form of ALS linked to chromosome 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193327 14511332 258352 20996 11179 SOD1 ALS ALS 18 3.2 superoxide dismutase (SOD1) SOD1 account for a familial form of ALS linked to chromosome 21q ( Rosen et al . 1993 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193328 14511332 258353 20996 11179 SOD1 SOD1 SOD1 4 2.9 Transgenic mice expressing mutant SOD1 develop a phenotype that mimics the clinical and pathological characteristics 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193329 14511332 258355 10437 5992 IL1B IL1BETA IL-1beta 2 1.5 Levels of IL-1beta IL-6 and tumour necrosis factor-alpha were found to be elevated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193330 14511332 258355 10463 6018 IL6 IL-6 IL-6 3 1.0 Levels of IL-1beta IL-6 and tumour necrosis factor-alpha were found to be elevated in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193331 14511332 258356 17610 9605 PTGS2 COX-2 COX-2 6 13.4 Very recently the proinflammatory enzyme cyclooxygenase-2 (COX-2) COX-2 was reported to be highly expressed in the spinal cord 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193332 14511332 258357 17610 9605 PTGS2 COX COX 2 2.2 Currently two COX isoforms are known namely COX-1 and COX-2 ( Vane et 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193333 14511332 258357 17609 9604 PTGS1 COX-1 COX-1 7 5.4 Currently two COX isoforms are known namely COX-1 and COX-2 ( Vane et al . 1998 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193334 14511332 258357 17610 9605 PTGS2 COX-2 COX-2 7 13.4 Currently two COX isoforms are known namely COX-1 and COX-2 ( Vane et al . 1998 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193335 14511332 258357 17610 9605 PTGS2 COX-2 COX-2 9 13.4 Currently two COX isoforms are known namely COX-1 and COX-2 ( Vane et al . 1998 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193336 14511332 258358 17609 9604 PTGS1 COX-1 COX-1 1 5.4 Whereas COX-1 mainly subserves _amp_#8216 house-keeping_amp_#8217 functions COX-2 is the product of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193337 14511332 258358 17610 9605 PTGS2 COX-2 COX-2 6 13.4 Whereas COX-1 mainly subserves _amp_#8216 house-keeping_amp_#8217 functions COX-2 is the product of an _amp_#8216 immediate-early gene_amp_#8217 that is 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193338 14511332 258359 17610 9605 PTGS2 COX-2 COX-2 3 13.4 Under normal conditions COX-2 expression is highly restricted to distinct organ systems including the 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193339 14511332 258359 17610 9605 PTGS2 COX-2 COX-2 33 13.4 and the eye ( Maihofner et al . 2001 but COX-2 expression can be dramatically increased in various tissues following the 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193340 14511332 258360 17610 9605 PTGS2 COX COX 10 2.2 Recently one of us demonstrated the constitutive expression of both COX isoforms in the spinal cord of rodents and a dramatic 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193341 14511332 258360 17610 9605 PTGS2 COX-2 COX-2 24 13.4 spinal cord of rodents and a dramatic induction of spinal COX-2 protein following peripheral nociceptive stimulation ( Maihofner et al . 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193342 14511332 258362 20996 11179 SOD1 ALS ALS 1 3.2 In ALS glutamatergic excitotoxicity was shown to contribute to motoneuron-death ( Fray 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193343 14511332 258363 20996 11179 SOD1 ALS ALS 9 3.2 Glutamate levels are elevated in the cerebrospinal fluid of ALS patients and inhibition of glial glutamate uptake has been used 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193344 14511332 258363 20996 11179 SOD1 ALS ALS 26 3.2 uptake has been used as an in vitro model for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193345 14511332 258364 17610 9605 PTGS2 COX-2 COX-2 4 13.4 Very recently inhibition of COX-2 was protective in a glutamate-mediated in vitro model of sALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193346 14511332 258365 17610 9605 PTGS2 COX-2 COX-2 11 13.4 et al . (2001 2001 described the immunohistochemical distribution of COX-2 in the spinal cord of mSOD1 mice over the progression 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193347 14511332 258365 20996 11179 SOD1 SOD1 mSOD1 17 3.2 the immunohistochemical distribution of COX-2 in the spinal cord of mSOD1 mice over the progression of the disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193348 14511332 258366 20996 11179 SOD1 ALS ALS 17 3.2 (PG PG E 2 level in post mortem samples of ALS cases as a marker for COX-2 activity 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193349 14511332 258366 17610 9605 PTGS2 COX-2 COX-2 23 13.4 post mortem samples of ALS cases as a marker for COX-2 activity 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193350 14511332 258367 17610 9605 PTGS2 COX COX 8 2.2 However the cellular localization and expression of both COX isoforms in human sALS remains unclear 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193351 14511332 258368 17609 9604 PTGS1 COX-1 COX-1 7 5.4 Therefore we compared the spinal expression of COX-1 and COX-2 in sALS and control patients by means of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193352 14511332 258368 17610 9605 PTGS2 COX-2 COX-2 7 13.4 Therefore we compared the spinal expression of COX-1 and COX-2 in sALS and control patients by means of 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193353 14511332 258368 17610 9605 PTGS2 COX-2 COX-2 9 13.4 Therefore we compared the spinal expression of COX-1 and COX-2 in sALS and control patients by means of immunohistochemistry 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193354 14511332 258369 17610 9605 PTGS2 COX-2 COX-2 7 13.4 We here demonstrate a high expression of COX-2 protein in spinal cord specimens of human sALS cases 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193355 14511332 258370 17609 9604 PTGS1 COX-1 COX-1 0 5.4 COX-1 expression did not differ between sALS and control tissues 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193356 14511332 258371 17610 9605 PTGS2 COX-2 COX-2 4 13.4 The increased expression of COX-2 was corroborated by a significantly higher concentration of PG E 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193357 14511332 258371 20996 11179 SOD1 ALS ALS 24 3.2 E 2 in the cerebrospinal fluid of patients diagnosed with ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193358 14511332 258374 20996 11179 SOD1 ALS ALS 12 3.2 spinal cord segment was examined in seven patients with sporadic ALS and seven age matched patients without any neurological disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193359 14511332 258379 17609 9604 PTGS1 COX-1 COX-1 7 5.4 Briefly goat polyclonal antisera raised against human COX-1 and COX-2 protein (Santa Santa Cruz Biotechnology Santa Cruz CA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193360 14511332 258379 17610 9605 PTGS2 COX-2 COX-2 7 13.4 Briefly goat polyclonal antisera raised against human COX-1 and COX-2 protein (Santa Santa Cruz Biotechnology Santa Cruz CA 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193361 14511332 258379 17610 9605 PTGS2 COX-2 COX-2 9 13.4 Briefly goat polyclonal antisera raised against human COX-1 and COX-2 protein (Santa Santa Cruz Biotechnology Santa Cruz CA were employed 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193362 14511332 258380 17609 9604 PTGS1 COX-1 COX-1 7 5.4 To further differentiate the cellular distributions of COX-1 and COX-2 proteins a double staining procedure using a mouse 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193363 14511332 258380 17610 9605 PTGS2 COX-2 COX-2 7 13.4 To further differentiate the cellular distributions of COX-1 and COX-2 proteins a double staining procedure using a mouse 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193364 14511332 258380 17610 9605 PTGS2 COX-2 COX-2 9 13.4 To further differentiate the cellular distributions of COX-1 and COX-2 proteins a double staining procedure using a mouse monoclonal antihuman 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193365 14511332 258380 8254 4235 GFAP GFAP GFAP 29 2.5 antibody to glial fibrillary acidic protein to label astrocytes (GFAP; GFAP DAKO Glostrup Denmark and a mouse monoclonal antihuman antibody to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193366 14511332 258380 10731 6149 ITGAM MAC-1 MAC-1 45 1.0 monoclonal antihuman antibody to macrophage antigen complex-1 labelling microglia (MAC-1, MAC-1 Serotec Raleigh NC was used 1 JUMiner_v2.2 1 0 0 2 6155 TotalCon:2<>6149|ITGAM|3684|Complete__6155|ITGB2|3689|Complete__<>AvaiableGeneRif=2<>BEST:6155|ITGB2|0.000652346761337419<>ScoreDetail__6155|ITGB2|0.000652346761337419__6149|ITGAM|0.000650158901652137__ 0 0 0 0 0 193367 14511332 258387 17609 9604 PTGS1 COX-1 COX-1 9 5.4 Specimens were coded and assessed observer-blinded for presence of COX-1 and COX-2 immunoreactivity (IR) IR 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193368 14511332 258387 17610 9605 PTGS2 COX-2 COX-2 9 13.4 Specimens were coded and assessed observer-blinded for presence of COX-1 and COX-2 immunoreactivity (IR) IR 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193369 14511332 258387 17610 9605 PTGS2 COX-2 COX-2 11 13.4 were coded and assessed observer-blinded for presence of COX-1 and COX-2 immunoreactivity (IR) IR 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193370 14511332 258400 19381 19440 SBDS SDS SDS-polyacrylamide 12 0.3 50 _amp_micro;g/lane) _amp_micro g lane was loaded on a 10% SDS-polyacrylamide gel and electroblotted onto nitrocellulose membranes (Schleicher Schleicher and Schuell 11 JUMiner_v2.2 1 2 sds 0 2 10691 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:10691|SDS|0.00047941921786179<>ScoreDetail__10691|SDS|0.00047941921786179__19440|SBDS|0.000459162067811292__ 0 0 0 0 0 193371 14511332 258401 17609 9604 PTGS1 COX-1 COX-1 7 5.4 Membranes were probed with polyclonal goat antihuman COX-1 or COX-2 serum (diluted diluted 1 1000 followed by a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193372 14511332 258401 17610 9605 PTGS2 COX-2 COX-2 9 13.4 Membranes were probed with polyclonal goat antihuman COX-1 or COX-2 serum (diluted diluted 1 1000 followed by a horseradish peroxidase 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193373 14511332 258402 3778 10620 CCL21 ECL ECL 6 0.0 Blots were developed with enhanced chemiluminescence (ECL) ECL detection reagents (Amersham, Amersham Arlington Heights IL and exposed to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193374 14511332 258405 20996 11179 SOD1 ALS ALS 5 3.2 Nine patients with clinically definite ALS were studied 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193375 14511332 258406 20996 11179 SOD1 ALS ALS 0 3.2 ALS was diagnosed on the basis of the El Escorial Criteria 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193376 14511332 258406 20996 11179 SOD1 ALS ALS 16 3.2 the El Escorial Criteria (World World Federation of Neurology of ALS ( Brooks 1994 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193377 14511332 258411 11629 6493 LAMC2 CSF CSF 3 0.0 The cerebrospinal fluid (CSF) CSF control group ( n = 9 consisted of patients with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193378 14511332 258412 11629 6493 LAMC2 CSF CSF 4 0.0 These specimens had normal CSF parameters i.e absence of pleocytosis intrathecal production of immunoglobulins and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193379 14511332 258414 11629 6493 LAMC2 CSF CSF 0 0.0 CSF was obtained at routine lumbar puncture for diagnostic purposes after 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193380 14511332 258418 17609 9604 PTGS1 COX-1 COX-1 31 5.4 immunohistochemistry we performed Western blotting experiments for the detection of COX-1 and COX-2 protein with spinal protein extracts from human donors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193381 14511332 258418 17610 9605 PTGS2 COX-2 COX-2 31 13.4 immunohistochemistry we performed Western blotting experiments for the detection of COX-1 and COX-2 protein with spinal protein extracts from human donors 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193382 14511332 258418 17610 9605 PTGS2 COX-2 COX-2 33 13.4 performed Western blotting experiments for the detection of COX-1 and COX-2 protein with spinal protein extracts from human donors with no 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193383 14511332 258419 17609 9604 PTGS1 COX-1 COX-1 17 5.4 cords (segments segments L1-L5 left lane run alongside purified sheep COX-1 protein (right right lane in a Western blot that has 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193384 14511332 258419 17609 9604 PTGS1 COX-1 COX-1 33 5.4 Western blot that has been incubated with the same polyclonal COX-1 antibody as that used for immunohistochemistry 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193385 14511332 258420 17609 9604 PTGS1 COX-1 COX-1 20 5.4 75 kDa consistent with the reported molecular mass of human COX-1 protein in the literature (74 74 kDa ( Vane et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193386 14511332 258421 17610 9605 PTGS2 COX-2 COX-2 13 13.4 the results of a similar experiment for the detection of COX-2 protein 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193387 14511332 258422 17610 9605 PTGS2 COX-2 COX-2 13 13.4 lane from human spinal cords were separated alongside purified sheep COX-2 protein (right right lane by SDS-PAGE blotted onto nitrocellulose membranes 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193388 14511332 258422 17610 9605 PTGS2 COX-2 COX-2 28 13.4 SDS-PAGE blotted onto nitrocellulose membranes and incubated with the same COX-2 antibody as that used for immunohistochemistry 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193389 14511332 258423 17610 9605 PTGS2 COX-2 COX-2 1 13.4 Unpurified COX-2 proteins derived from either cell lysates or tissues typically produce 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193390 14511332 258424 17610 9605 PTGS2 COX-2 COX-2 11 13.4 single band at 75 kDa was detected for the purified COX-2 protein 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193391 14511332 258425 17610 9605 PTGS2 COX COX 10 2.2 To exclude potential crossreactions between the antibodies for the two COX isoforms we determined the specifity with purified COX-1 and COX-2 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193392 14511332 258425 17609 9604 PTGS1 COX-1 COX-1 18 5.4 the two COX isoforms we determined the specifity with purified COX-1 and COX-2 protein by Western blotting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193393 14511332 258425 17610 9605 PTGS2 COX-2 COX-2 18 13.4 the two COX isoforms we determined the specifity with purified COX-1 and COX-2 protein by Western blotting 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193394 14511332 258425 17610 9605 PTGS2 COX-2 COX-2 20 13.4 COX isoforms we determined the specifity with purified COX-1 and COX-2 protein by Western blotting 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193395 14511332 258426 17609 9604 PTGS1 COX-1 COX-1 8 5.4 Figure 1C shows that the goat antihuman polyclonal COX-1 antibody exclusively detected COX-1 protein and not COX-2 protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193396 14511332 258426 17609 9604 PTGS1 COX-1 COX-1 12 5.4 shows that the goat antihuman polyclonal COX-1 antibody exclusively detected COX-1 protein and not COX-2 protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193397 14511332 258426 17610 9605 PTGS2 COX-2 COX-2 16 13.4 antihuman polyclonal COX-1 antibody exclusively detected COX-1 protein and not COX-2 protein 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193398 14511332 258427 17610 9605 PTGS2 COX-2 COX-2 15 13.4 from a similar experiment in which the goat antihuman polyclonal COX-2 antibody detected only COX-2 protein and not COX-1 protein 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193399 14511332 258427 17610 9605 PTGS2 COX-2 COX-2 19 13.4 in which the goat antihuman polyclonal COX-2 antibody detected only COX-2 protein and not COX-1 protein 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193400 14511332 258427 17609 9604 PTGS1 COX-1 COX-1 23 5.4 antihuman polyclonal COX-2 antibody detected only COX-2 protein and not COX-1 protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193401 14511332 258431 17610 9605 PTGS2 COX COX-immunoreactivity 0 0.0 COX-immunoreactivity 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 193402 14511332 258432 17610 9605 PTGS2 COX-2 COX-2 13 13.4 only a few motor neurons and interneurons were immunoreactive for COX-2 protein ( Fig 2B 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193403 14511332 258438 17610 9605 PTGS2 COX COX-2-positive 12 0.0 number of neurons with COX-2-IR was counted the percentage of COX-2-positive motor neurons and interneurons was found to be significantly increased 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 193404 14511332 258439 17610 9605 PTGS2 COX-2 COX-2 3 13.4 Furthermore expression of COX-2 was found to be enhanced in sALS cases compared to 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193405 14511332 258440 8254 4235 GFAP GFAP GFAP 17 2.5 cells counterstaining with an antibody raised against the astrocyte marker GFAP was performed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193406 14511332 258441 8254 4235 GFAP GFAP GFAP 6 2.5 As demonstrated by the coexpression with GFAP glial COX-2 expression was predominantly found in astrocytes ( Fig 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193407 14511332 258441 17610 9605 PTGS2 COX-2 COX-2 8 13.4 As demonstrated by the coexpression with GFAP glial COX-2 expression was predominantly found in astrocytes ( Fig 2H 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193408 14511332 258442 10731 6149 ITGAM MAC-1 MAC-1 23 1.0 microglia as shown by its coexpression with the microglia marker MAC-1 ( Fig 2I 1 JUMiner_v2.2 1 0 0 2 6155 TotalCon:2<>6149|ITGAM|3684|Complete__6155|ITGB2|3689|Complete__<>AvaiableGeneRif=2<>BEST:6155|ITGB2|0.000652346761337419<>ScoreDetail__6155|ITGB2|0.000652346761337419__6149|ITGAM|0.000650158901652137__ 0 0 0 0 0 193409 14511332 258443 17610 9605 PTGS2 COX-2 COX-2 5 13.4 Overall the glial expression of COX-2 was significantly increased in sALS cases (0.71 0.71 _amp_plusmn 0.5 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193410 14511332 258445 17609 9604 PTGS1 COX-1 COX-1 2 5.4 Expression of COX-1 protein was predominantly confined to some small cells with the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193411 14511332 258446 17609 9604 PTGS1 COX-1 COX-1 9 5.4 This could also be demonstrated by the costaining of COX-1 with the microglial marker MAC-1 ( Fig 2L 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193412 14511332 258446 10731 6149 ITGAM MAC-1 MAC-1 14 1.0 demonstrated by the costaining of COX-1 with the microglial marker MAC-1 ( Fig 2L 1 JUMiner_v2.2 1 0 0 2 6155 TotalCon:2<>6149|ITGAM|3684|Complete__6155|ITGB2|3689|Complete__<>AvaiableGeneRif=2<>BEST:6155|ITGB2|0.000652346761337419<>ScoreDetail__6155|ITGB2|0.000652346761337419__6149|ITGAM|0.000650158901652137__ 0 0 0 0 0 193413 14511332 258449 11629 6493 LAMC2 CSF CSF 21 0.0 sALS cases The individual concentrations of PG E 2 in CSF along with the means and standard deviations are shown for 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193414 14511332 258454 17610 9605 PTGS2 COX-2 COX-2 14 13.4 reduction of neurons in the spinal cord the percentage of COX-2 expressing motor neurons and interneurons was increased in sALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193415 14511332 258455 17610 9605 PTGS2 COX-2 COX-2 4 13.4 Secondly glial expression of COX-2 was enhanced in sALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193416 14511332 258456 17609 9604 PTGS1 COX-1 COX-1 1 5.4 Thirdly COX-1 expression was predominately confined to glial cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193417 14511332 258458 11629 6493 LAMC2 CSF CSF 8 0.0 Fourthly higher PG-E 2 levels were found in CSF specimens of sALS patients compared to controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193418 14511332 258459 17610 9605 PTGS2 COX-2 COX-2 0 13.4 COX-2 overexpression in sALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193419 14511332 258460 17610 9605 PTGS2 COX-2 COX-2 2 13.4 Expression of COX-2 in human diseases is a topic of considerable interest with 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193420 14511332 258460 17610 9605 PTGS2 COX-2 COX-2 19 13.4 of considerable interest with regard to the recent development of COX-2 selective inhibitors ( Hawkey 1999 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193421 14511332 258461 20996 11179 SOD1 ALS ALS 1 3.2 Regarding ALS Drachman and Rothstein ( Drachman _amp_ Rothstein 2000 demonstrated a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193422 14511332 258461 17610 9605 PTGS2 COX-2 COX-2 16 13.4 ( Drachman _amp_ Rothstein 2000 demonstrated a beneficial effect of COX-2 inhibition in an in vitro model while Almer et al 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193423 14511332 258462 17610 9605 PTGS2 COX-2 COX-2 6 13.4 (2001 2001 demonstrated a role for COX-2 in mutant SOD1 mice and Yasojima et al 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193424 14511332 258462 20996 11179 SOD1 SOD1 SOD1 9 2.9 (2001 2001 demonstrated a role for COX-2 in mutant SOD1 mice and Yasojima et al 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193425 14511332 258463 17610 9605 PTGS2 COX-2 COX-2 5 13.4 (2001 2001 showed up-regulation of COX-2 mRNA in spinal cord specimens of sALS cases 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193426 14511332 258464 17610 9605 PTGS2 COX-2 COX-2 10 13.4 Recently two animal studies demonstrated a beneficial effect of selective COX-2 inhibition in mouse models of ALS ( Drachman et al 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193427 14511332 258464 20996 11179 SOD1 ALS ALS 16 3.2 beneficial effect of selective COX-2 inhibition in mouse models of ALS ( Drachman et al . 2002 Pompl et al . 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193428 14511332 258465 17610 9605 PTGS2 COX-2 COX-2 5 13.4 However the cellular origin of COX-2 up-regulation in human sALS has so far not been delineated 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193429 14511332 258466 17609 9604 PTGS1 COX-1 COX-1 10 5.4 Furthermore no study has yet investigated the cellular expression of COX-1 in sALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193430 14511332 258467 17610 9605 PTGS2 COX-2 COX-2 11 13.4 we provide immunohistochemical evidence for a dramatic increase in spinal COX-2 expression in motor neurons interneurons and glial cells in sALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193431 14511332 258468 17610 9605 PTGS2 COX-2 COX-2 0 13.4 COX-2 was also observed in motor neurons of control specimens the 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193432 14511332 258469 17610 9605 PTGS2 COX-2 COX-2 9 13.4 This agrees with reports on the constitutive expression of COX-2 in the spinal cord of rodents and the localization of 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193433 14511332 258469 17610 9605 PTGS2 COX-2 COX-2 20 13.4 in the spinal cord of rodents and the localization of COX-2 protein determined electron microscopically ( Maihofner et al . 2000b 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193434 14511332 258470 17610 9605 PTGS2 COX-2 COX-2 3 13.4 In normal conditions COX-2 derived PGs are assumed to play homeostatic functions ( Beiche 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193435 14511332 258471 17610 9605 PTGS2 COX-2 COX-2 6 13.4 Nevertheless the reason for the dramatic COX-2 overexpression in sALS is unknown 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193436 14511332 258472 11629 6493 LAMC2 CSF CSF 16 0.0 interplay with glutamate levels of which are elevated in the CSF of sALS patients ( Plaitakis et al . 1988 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193437 14511332 258473 17610 9605 PTGS2 COX-2 COX-2 3 13.4 In pain models COX-2 protein was induced following glutamatergic stimulation ( Maihofner et al 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193438 14511332 258475 17610 9605 PTGS2 COX-2 COX-2 9 13.4 NF-kappa B NF-kappa B in particular is crucial for COX-2 induction in several cell types ( Vane et al . 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193439 14511332 258476 17610 9605 PTGS2 COX-2 COX-2 8 13.4 Cytokines could also contribute to high expression of COX-2 in sALS particularly IL-1beta and IL-6 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193440 14511332 258476 10437 5992 IL1B IL1BETA IL-1beta 12 1.5 also contribute to high expression of COX-2 in sALS particularly IL-1beta and IL-6 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193441 14511332 258476 10463 6018 IL6 IL-6 IL-6 14 1.0 to high expression of COX-2 in sALS particularly IL-1beta and IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193442 14511332 258477 17610 9605 PTGS2 COX-2 COX-2 5 13.4 Both are known inducers of COX-2 expression and their concentrations are elevated in the CSF of 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193443 14511332 258477 20996 11179 SOD1 ALS ALS 16 3.2 expression and their concentrations are elevated in the CSF of ALS cases ( Sekizawa et al . 1998 Vane et al 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193444 14511332 258477 11629 6493 LAMC2 CSF CSF 14 0.1 of COX-2 expression and their concentrations are elevated in the CSF of ALS cases ( Sekizawa et al . 1998 Vane 6 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 193445 14511332 258478 10437 5992 IL1B IL1BETA IL-1beta 3 1.5 Interestingly inhibition of IL-1beta also attenuates the loss of motor neurons in mSOD1 mice 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193446 14511332 258478 20996 11179 SOD1 SOD1 mSOD1 12 3.2 of IL-1beta also attenuates the loss of motor neurons in mSOD1 mice ( Friedlander et al . 1997 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193447 14511332 258479 10437 5992 IL1B IL1BETA IL-1beta 0 1.5 IL-1beta and IL-6 are assumed to derive from glia 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193448 14511332 258479 10463 6018 IL6 IL-6 IL-6 2 1.0 IL-1beta and IL-6 are assumed to derive from glia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193449 14511332 258480 20996 11179 SOD1 ALS ALS 7 3.2 Gliosis is a common histological hallmark of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193450 14511332 258481 17610 9605 PTGS2 COX-2 COX-2 8 13.4 Consistently we demonstrated a significantly higher expression of COX-2 in glial cells 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193451 14511332 258482 20996 11179 SOD1 SOD1 mSOD1 7 3.2 In agreement with a study in transgenic mSOD1 mice ( Almer et al . 2001 COX-2 was found 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193452 14511332 258482 17610 9605 PTGS2 COX-2 COX-2 16 13.4 in transgenic mSOD1 mice ( Almer et al . 2001 COX-2 was found to be predominantly expressed in astrocytes and not 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193453 14511332 258483 10437 5992 IL1B IL1BETA IL-1beta 8 1.5 This might be explained by the capability of IL-1beta to induce COX-2 in astrocytes but not in microglia cells 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193454 14511332 258483 17610 9605 PTGS2 COX-2 COX-2 11 13.4 might be explained by the capability of IL-1beta to induce COX-2 in astrocytes but not in microglia cells ( Vane et 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193455 14511332 258484 17610 9605 PTGS2 COX-2 COX-2 0 13.4 COX-2 expression in the astroglia of rodents has been shown previously 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193456 14511332 258486 17610 9605 PTGS2 COX-2 COX-2 14 13.4 reduction in the number of interneurons in our sALS cases COX-2 expression was also found to be increased in this cell 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193457 14511332 258487 20996 11179 SOD1 ALS ALS 30 3.2 and an active involvement of interneurons in the pathology of ALS ( Rowland _amp_ Shneider 2001 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193458 14511332 258488 17610 9605 PTGS2 COX COX 18 2.2 match those of a previous study investigating the expression of COX proteins in mSOD1 mice 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193459 14511332 258488 20996 11179 SOD1 SOD1 mSOD1 21 3.2 a previous study investigating the expression of COX proteins in mSOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193460 14511332 258490 17610 9605 PTGS2 COX-2 COX-2 5 13.4 (2001 2001 also found that COX-2 was present in motor neurons and predominantly in astroglia although 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193461 14511332 258490 17609 9604 PTGS1 COX-1 COX-1 20 5.4 neurons and predominantly in astroglia although no apparent differences in COX-1 expression were seen between mSOD1 mice and controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193462 14511332 258490 20996 11179 SOD1 SOD1 mSOD1 25 3.2 although no apparent differences in COX-1 expression were seen between mSOD1 mice and controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193463 14511332 258491 20996 11179 SOD1 ALS ALS 17 3.2 tissues and that previously obtained in an experimental model of ALS in the mouse are in excellent agreement 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193464 14511332 258497 20996 11179 SOD1 ALS ALS 10 3.2 Despite a significant reduction in the number of neurons in ALS specimens the proportion of motoneurons and interneurons was virtually the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193465 14511332 258498 17610 9605 PTGS2 COX-2 COX-2 15 13.4 that misclassification of neurons led to the high expression of COX-2 protein in sALS presented here 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193466 14511332 258500 17609 9604 PTGS1 COX-1 COX-1 48 5.4 . 2003 and were shown to be specific for the COX-1 and COX-2 protein respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193467 14511332 258500 17610 9605 PTGS2 COX-2 COX-2 48 13.4 . 2003 and were shown to be specific for the COX-1 and COX-2 protein respectively 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193468 14511332 258500 17610 9605 PTGS2 COX-2 COX-2 50 13.4 and were shown to be specific for the COX-1 and COX-2 protein respectively 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193469 14511332 258501 17610 9605 PTGS2 COX COX 17 2.2 of the antibodies and their capability to detect the respective COX isoforms in human spinal cord extracts by Western blotting 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193470 14511332 258503 17609 9604 PTGS1 COX-1 COX-1 11 5.4 have intentionally focused on the in situ expression of both COX-1 and COX-2 proteins in human ALS spinal cords 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193471 14511332 258503 17610 9605 PTGS2 COX-2 COX-2 11 13.4 have intentionally focused on the in situ expression of both COX-1 and COX-2 proteins in human ALS spinal cords 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193472 14511332 258503 17610 9605 PTGS2 COX-2 COX-2 13 13.4 focused on the in situ expression of both COX-1 and COX-2 proteins in human ALS spinal cords 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193473 14511332 258503 20996 11179 SOD1 ALS ALS 17 3.2 situ expression of both COX-1 and COX-2 proteins in human ALS spinal cords 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193474 14511332 258505 17610 9605 PTGS2 COX COX 10 2.2 Therefore this study provides necessary data regarding the expression of COX isoforms in human ALS 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193475 14511332 258505 20996 11179 SOD1 ALS ALS 14 3.2 necessary data regarding the expression of COX isoforms in human ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193476 14511332 258506 20996 11179 SOD1 ALS ALS 19 3.2 of PG-E 2 in the CSF of patients diagnosed for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193477 14511332 258506 11629 6493 LAMC2 CSF CSF 14 0.0 were confirmed by the measurement of PG-E 2 in the CSF of patients diagnosed for ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193478 14511332 258507 20996 11179 SOD1 ALS ALS 8 3.2 PG-E 2 levels were significantly increased in the ALS group 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193479 14511332 258508 17610 9605 PTGS2 COX COX-activity 9 0.0 Therefore measurement of PG-E 2 as a marker for COX-activity may serve as an additional independent method 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 193480 14511332 258511 17610 9605 PTGS2 COX-2 COX-2 19 13.4 with the results of two recent animal studies where selective COX-2 inhibition was found to be protective against motor neuron death 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193481 14511332 258512 17610 9605 PTGS2 COX-2 COX-2 3 13.4 A role for COX-2 in the pathogenesis of sALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193482 14511332 258513 17610 9605 PTGS2 COX-2 COX-2 5 13.4 What is the significance of COX-2 overexpression in ALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193483 14511332 258513 20996 11179 SOD1 ALS ALS 8 3.2 What is the significance of COX-2 overexpression in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193484 14511332 258514 17610 9605 PTGS2 COX-2 COX-2 7 13.4 There are several lines of evidence that COX-2 might play a role in the pathogenesis of ALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193485 14511332 258514 20996 11179 SOD1 ALS ALS 16 3.2 that COX-2 might play a role in the pathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193486 14511332 258515 17610 9605 PTGS2 COX-2 COX-2 5 13.4 Firstly application of a selective COX-2 inhibitor in an in vitro organotypic model of ALS protected 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193487 14511332 258515 20996 11179 SOD1 ALS ALS 14 3.2 selective COX-2 inhibitor in an in vitro organotypic model of ALS protected against the loss of motor neurons in this system 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193488 14511332 258516 17610 9605 PTGS2 COX-2 COX-2 15 13.4 in two in vivo studies where application of a selective COX-2 inhibitor protected against motor neuron degeneration and prolonged survival in 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193489 14511332 258516 20996 11179 SOD1 ALS ALS 30 3.2 neuron degeneration and prolonged survival in transgenic mouse models of ALS ( Drachman et al . 2002 Pompl et al . 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193490 14511332 258517 17610 9605 PTGS2 COX-2 COX-2 7 13.4 Thirdly based on the action of PGs COX-2 could promote inflammatory processes in ALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193491 14511332 258517 20996 11179 SOD1 ALS ALS 13 3.2 the action of PGs COX-2 could promote inflammatory processes in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193492 14511332 258518 20996 11179 SOD1 ALS ALS 7 3.2 Although classical cellular inflammation is absent in ALS there is mounting evidence that inflammatory related processes may be 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193493 14511332 258520 17610 9605 PTGS2 COX-2 COX-2 1 13.4 Therefore COX-2 derived PGs could play a role in glutamate excitotoxicity which 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193494 14511332 258520 20996 11179 SOD1 ALS ALS 17 3.2 role in glutamate excitotoxicity which is postulated to occur in ALS ( Rowland _amp_ Shneider 2001 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193495 14511332 258521 17610 9605 PTGS2 COX-2 COX-2 31 13.4 potentiation of kainic acid induced excitotoxicity in transgenic mice overexpressing COX-2 protein 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193496 14511332 258522 17610 9605 PTGS2 COX-2 COX-2 1 13.4 Fourthly COX-2 may also be involved in the production of reactive oxygen 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193497 14511332 258523 17610 9605 PTGS2 COX COX 0 2.2 COX enzymes are bifunctional proteins 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193498 14511332 258526 17610 9605 PTGS2 COX COX 4 2.2 The peroxidase activity of COX is nonspecific and can reduce several different hydroperoxides while co-oxidizing 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193499 14511332 258527 17610 9605 PTGS2 COX-2 COX-2 1 13.4 Finally COX-2 appears to be involved in neuronal cell cycle regulation 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193500 14511332 258529 17610 9605 PTGS2 COX-2 COX-2 23 13.4 kinase (INK) INK p18INK4 is a downstream target of neuronal COX-2 expression p18INK4 inhibits CDK 4 6 which is in turn 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193501 14511332 258530 17610 9605 PTGS2 COX-2 COX-2 1 13.4 Therefore COX-2 inhibition might attenuate apoptotic damage in neurodegenerative diseases 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193502 14511332 258531 17610 9605 PTGS2 COX-2 COX-2 4 13.4 However the specifity of COX-2 expression for ALS has to be questioned 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193503 14511332 258531 20996 11179 SOD1 ALS ALS 7 3.2 However the specifity of COX-2 expression for ALS has to be questioned 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193504 14511332 258532 17610 9605 PTGS2 COX-2 COX-2 1 13.4 Increased COX-2 levels were also shown for Alzheimer's disease Parkinson's disease epilepsy 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193505 14511332 258533 17610 9605 PTGS2 COX-2 COX-2 8 13.4 Therefore we would explicitly like to state that COX-2 expression seems to be a common endpoint in neurodegeneration rather 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193506 14511332 258533 20996 11179 SOD1 ALS ALS 24 3.2 common endpoint in neurodegeneration rather than the actual cause of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193507 14511332 258534 17610 9605 PTGS2 COX-2 COX-2 6 13.4 Furthermore there is the possibility that COX-2 expression might be protective and antiapoptotic 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193508 14511332 258536 17610 9605 PTGS2 COX-2 COX-2 12 13.4 of us was able to show that the expression of COX-2 in CRC parallels the expression of IL-1 beta and IL-6 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193509 14511332 258536 10437 5992 IL1B IL-1 IL-1 19 1.5 the expression of COX-2 in CRC parallels the expression of IL-1 beta and IL-6 in CRC ( Maihofner et al . 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193510 14511332 258536 10463 6018 IL6 IL-6 IL-6 22 1.0 COX-2 in CRC parallels the expression of IL-1 beta and IL-6 in CRC ( Maihofner et al . 2003 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193511 14511332 258537 17610 9605 PTGS2 COX-2 COX-2 3 13.4 In this context COX-2 is thought to be actively involved in carcinogenesis and antiapoptosis 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193512 14511332 258538 17610 9605 PTGS2 COX-2 COX-2 17 13.4 by the immunohistochemical results presented here the exact role of COX-2 in the pathogenesis of human ALS still remains to be 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193513 14511332 258538 20996 11179 SOD1 ALS ALS 23 3.2 the exact role of COX-2 in the pathogenesis of human ALS still remains to be elucidated 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193514 14511332 258539 20996 11179 SOD1 ALS ALS 9 3.2 Clinical trials are underway in the United States (North-east North-east ALS consortium to test a potential benefit of selective COX-2 inhibition 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193515 14511332 258539 17610 9605 PTGS2 COX-2 COX-2 18 13.4 North-east ALS consortium to test a potential benefit of selective COX-2 inhibition in human ALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193516 14511332 258539 20996 11179 SOD1 ALS ALS 22 3.2 test a potential benefit of selective COX-2 inhibition in human ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193517 14511332 258540 17609 9604 PTGS1 COX-1 COX-1 2 5.4 Expression of COX-1 protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193518 14511332 258541 17610 9605 PTGS2 COX-2 COX-2 4 13.4 In contrast to the COX-2 protein COX-1 expression was predominantly found in microglia cells and 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193519 14511332 258541 17609 9604 PTGS1 COX-1 COX-1 6 5.4 In contrast to the COX-2 protein COX-1 expression was predominantly found in microglia cells and showed no 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193520 14511332 258542 17609 9604 PTGS1 COX-1 COX-1 2 5.4 Expression of COX-1 in microglia is consistent with our previous animal study and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193521 14511332 258545 17609 9604 PTGS1 COX-1 COX-1 8 5.4 (2001 2001 who reported a similar content of COX-1 mRNA in sALS and controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193522 14511332 258546 17609 9604 PTGS1 COX-1 COX-1 4 5.4 The unaltered expression of COX-1 in sALS implies that there is no or only a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193523 14511332 258546 20996 11179 SOD1 ALS ALS 24 3.2 a minor role for this isoform in the pathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193524 14511332 258548 17610 9605 PTGS2 COX-2 COX-2 9 13.4 Alzheimer disease ( Pasinetti _amp_ Aisen 1998 where COX-2 was found to be the pivotal isoform involved in the 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193525 14511332 258549 17610 9605 PTGS2 COX COX 14 2.2 for the first time the in situ expression of both COX proteins in the spinal cords of human sALS specimens 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193526 14511332 258550 17610 9605 PTGS2 COX-2 COX-2 2 13.4 Expression of COX-2 protein was markedly increased in the motoneurons interneurons and glial 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193527 14511332 258551 17609 9604 PTGS1 COX-1 COX-1 15 5.4 was detected between controls and sALS with regard to the COX-1 protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193528 14511332 258552 17610 9605 PTGS2 COX-2 COX-2 7 13.4 Based on the beneficial effects of selective COX-2 inhibition in models of ALS the results of this and 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193529 14511332 258552 20996 11179 SOD1 ALS ALS 12 3.2 the beneficial effects of selective COX-2 inhibition in models of ALS the results of this and other studies might give a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193530 14511332 258552 17610 9605 PTGS2 COX-2 COX-2 33 13.4 rationale for clinical investigations on potential positive effects of selective COX-2 inhibitors in human sALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193531 14511332 258556 20996 11179 SOD1 ALS ALS 0 3.2 ALS amyotrophic lateral sclerosis COX cyclooxygenase CSF cerebrospinal fluid GFAP glial 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000844058375623846<>ScoreDetail__5468|IGFALS|0.000553428263731004__11179|SOD1|0.000844058375623846__ 0 0 0 0 0 193532 14511332 258556 17610 9605 PTGS2 COX COX 4 2.2 ALS amyotrophic lateral sclerosis COX cyclooxygenase CSF cerebrospinal fluid GFAP glial fibrillary acidic protein IR 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 193533 14511332 258556 8254 4235 GFAP GFAP GFAP 9 2.5 ALS amyotrophic lateral sclerosis COX cyclooxygenase CSF cerebrospinal fluid GFAP glial fibrillary acidic protein IR immunoreactivity PG prostaglandins SOD superoxide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193534 14511332 258556 20996 11179 SOD1 SOD SOD 18 2.9 fluid GFAP glial fibrillary acidic protein IR immunoreactivity PG prostaglandins SOD superoxide dismutase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 193535 14511332 258556 11629 6493 LAMC2 CSF CSF 6 0.1 ALS amyotrophic lateral sclerosis COX cyclooxygenase CSF cerebrospinal fluid GFAP glial fibrillary acidic protein IR immunoreactivity PG 6 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 195575 14556941 260916 13374 7197 MOG MOG MOG 56 1.9 clinical features of MS-like disease in myelin oligodendrocyte glycoprotein (MOG)-induced MOG -induced EAE in mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195576 14556941 260917 13374 7197 MOG MOG MOG-induced 24 1.9 appearance of clinical symptoms dramatically reduced the clinical severity of MOG-induced EAE while all the MOG-immunized control mice developed significant clinical 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195577 14556941 260917 13374 7197 MOG MOG MOG-immunized 29 1.9 reduced the clinical severity of MOG-induced EAE while all the MOG-immunized control mice developed significant clinical manifestations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195578 14556941 260918 13374 7197 MOG MOG MOG-treated 14 1.9 demonstrated only mild focal inflammation and less demyelination compared to MOG-treated mice using histological methods 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195579 14556941 260920 13374 7197 MOG MOG MOG 14 1.9 in the immune system potency as T-cell proliferative responses to MOG were similar in both groups 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195580 14556941 260921 13374 7197 MOG MOG MOG-induced 27 1.9 damage in the CNS and attenuate the clinical severity of MOG-induced EAE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195581 14556941 260922 20996 11179 SOD1 ALS ALS 12 0.0 that riluzole a drug used in amyotrophic lateral sclerosis (ALS), ALS might be beneficial for the treatment of MS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00106563979929848<>ScoreDetail__5468|IGFALS|0.000359823172612316__11179|SOD1|0.00106563979929848__ 0 0 0 0 0 195582 14556941 260934 11629 6493 LAMC2 CSF CSF 11 0.3 Moreover Stover et al 46 demonstrated an increase in CSF glutamate levels in MS patients which correlated with the severity 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 195583 14556941 260936 20996 11179 SOD1 ALS ALS 11 0.0 hypothesis in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) ALS suggests that anti-glutamatergic agents might be neuroprotective 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00106563979929848<>ScoreDetail__5468|IGFALS|0.000359823172612316__11179|SOD1|0.00106563979929848__ 0 0 0 0 0 195584 14556941 260937 20996 11179 SOD1 ALS ALS 20 0.0 to be protective in several models of neurodegenerative diseases including ALS 19 and 20 Parkinson_amp_#x2019 s 1 3 5 9 and 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00106563979929848<>ScoreDetail__5468|IGFALS|0.000359823172612316__11179|SOD1|0.00106563979929848__ 0 0 0 0 0 195585 14556941 260941 20996 11179 SOD1 ALS ALS 18 0.0 was approved by the US Food and Drug Administration for ALS therapy 8 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00106563979929848<>ScoreDetail__5468|IGFALS|0.000359823172612316__11179|SOD1|0.00106563979929848__ 0 0 0 0 0 195586 14556941 260942 13374 7197 MOG MOG MOG 20 1.9 insult to neurons and axons in myelin oligodendrocyte glycoprotein (MOG)-induced MOG -induced EAE in C3H.SW mice a chronic model which appears 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195587 14556941 260952 13374 7197 MOG MOG MOG 14 1.9 with the peptide encompassing amino acids 35_amp_#x2013 55 of rat MOG 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195588 14556941 260954 13374 7197 MOG MOG MOG 18 1.9 with a 200 _amp_#x3bc l emulsion containing 75 _amp_#x3bc g MOG peptide (300 300 _amp_#x3bc g in the case of C57/bl) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195589 14556941 260965 13374 7197 MOG MOG MOG 5 1.9 Spinal cords from riluzole-treated and MOG mice were dissected 28 days after immunization with pMOG 35_amp_#x2013 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195590 14556941 260993 4863 2311 CPM CPM CPM 16 0.0 H -thymidine incorporation expressed as mean counts per minute (CPM) CPM of triplicate wells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195591 14556941 260996 13374 7197 MOG MOG MOG- 17 1.9 severity of EAE following pMOG 35_amp_#x2013 55 induction between the MOG- and riluzole-treated mice groups was evaluated using Student_amp_#x2019 s t 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195592 14556941 261001 13374 7197 MOG MOG MOG 14 1.9 when it was administered together with the first injection of MOG was shown to be beneficial in reducing clinical symptoms ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195593 14556941 261002 13374 7197 MOG MOG MOG 17 1.9 twice a day was given 14 days after the first MOG injection at the appearance of symptoms 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195594 14556941 261003 13374 7197 MOG MOG MOG 15 1.9 riluzole-treated mice ( n =10 as measured 30 days after MOG injection was much lower than for the MOG-treated mice (1.18_amp_#xb1;0.47 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195595 14556941 261003 13374 7197 MOG MOG MOG-treated 23 1.9 days after MOG injection was much lower than for the MOG-treated mice (1.18_amp_#xb1;0.47 1.18_amp_#xb1 0.47 vs 2.31_amp_#xb1 0.23 P _amp_#x3c 0.03 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195596 14556941 261009 13374 7197 MOG MOG MOG 3 1.9 Twenty-seven days after MOG injection there were marked differences between the control (CC) CC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195597 14556941 261010 13374 7197 MOG MOG MOG-induced 12 1.9 of the 10 riluzole-treated (RR) RR mice remained resistant to MOG-induced EAE and remained disease free ( P =0.001 using _amp_#x3c7 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195598 14556941 261016 13374 7197 MOG MOG MOG 9 1.9 Representative H_amp_#x26 E staining of spinal cords from five immunized MOG mice 28 days after immunization revealed marked multifocal lymphohistiocytic inflammation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195599 14556941 261019 13374 7197 MOG MOG MOG-treated 15 1.9 in the number of lymphocytes in the spinal cord of MOG-treated mice compared to naive mice as indicated by arbitrary units 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195600 14556941 261019 13374 7197 MOG MOG MOG-treated 48 1.9 was dramatically reduced in riluzole-treated mice as compared to the MOG-treated group (0.036_amp_#xb1;0.007 0.036_amp_#xb1 0.007 vs 0.072_amp_#xb1 0.01 P _amp_#x3c 0.01 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195601 14556941 261020 13374 7197 MOG MOG MOG-treated 3 1.9 Inflammation in the MOG-treated mice was associated with myelin loss as indicated by LFB 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195602 14556941 261023 13374 7197 MOG MOG MOG-treated 7 1.9 Axonal staining of spinal cord sections from MOG-treated mice showed severe axonal damage using Bielshowesky_amp_#x2019 s method ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195603 14556941 261024 13374 7197 MOG MOG MOG-treated 22 1.9 we found marked axonal loss in the spinal cords of MOG-treated mice compared to naive mice (0.44_amp_#xb1;0.03 0.44_amp_#xb1 0.03 vs 0.65_amp_#xb1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195604 14556941 261024 13374 7197 MOG MOG MOG-treated 45 1.9 the riluzole-treated mice axonal integrity was preserved compared to the MOG-treated group (0.54_amp_#xb1;0.02 0.54_amp_#xb1 0.02 vs 0.44_amp_#xb1 0.03 P _amp_#x3c 0.02 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195605 14556941 261026 13374 7197 MOG MOG MOG-treated 8 1.9 Based on such testing the spinal cords of MOG-treated mice showed an increase of abnormal dephosphorylated NF-H ( Fig 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195606 14556941 261026 14280 7737 NEFH NFH NF-H 16 0.3 cords of MOG-treated mice showed an increase of abnormal dephosphorylated NF-H ( Fig 2G while minimal abnormal dephosphorylation was observed in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195607 14556941 261027 13374 7197 MOG MOG MOG-treated 20 1.9 Pro Plus analysis we found massive axonal damage in the MOG-treated mice compared to naive mice (0.03_amp_#xb1;0.003 0.03_amp_#xb1 0.003 vs 0.0005_amp_#xb1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195608 14556941 261027 13374 7197 MOG MOG MOG-treated 51 1.9 in the area stained by SMI-32 as compared to the MOG-treated group (0.0006_amp_#xb1;0.0001 0.0006_amp_#xb1 0.0001 vs 0.03_amp_#xb1 0.003 P _amp_#x3c 0.0001 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195609 14556941 261028 13374 7197 MOG MOG MOG-treated 9 1.9 We compared the T-cell response in the riluzole- and MOG-treated mice groups to rule out the possibility that the observed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195610 14556941 261029 13374 7197 MOG MOG MOG-treated 2 1.9 Riluzole-treated and MOG-treated mice (three three in each group were immunized with pMOG 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195611 14556941 261030 13374 7197 MOG MOG MOG 16 1.9 Fig 4 the in vitro primary proliferative response of both MOG and riluzole-treated mice against pMOG 35_amp_#x2013 55 was similar 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195612 14556941 261034 13374 7197 MOG MOG MOG-induced 11 1.9 study shows that riluzole-treated C3H.SW mice are highly resistant to MOG-induced chronic EAE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195613 14556941 261038 14280 7737 NEFH NFH NF-H 17 0.3 demonstrated axonal disruption indicating a large increase of abnormally dephosphorylated NF-H in MOG-immunized spinal cords in the riluzole-treated mice there was 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195614 14556941 261038 13374 7197 MOG MOG MOG-immunized 19 1.9 disruption indicating a large increase of abnormally dephosphorylated NF-H in MOG-immunized spinal cords in the riluzole-treated mice there was minimal abnormal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195615 14556941 261039 13374 7197 MOG MOG MOG-immunized 15 1.9 for pMOG 35_amp_#x2013 55 was similar in the riluzole-treated and MOG-immunized mice suggesting that the beneficial effect of riluzole is probably 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 195616 14556941 261053 20996 11179 SOD1 ALS ALS 42 0.0 Parkinson_amp_#x2019 s disease 1 3 5 9 and 10 and ALS 19 and 20 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00106563979929848<>ScoreDetail__5468|IGFALS|0.000359823172612316__11179|SOD1|0.00106563979929848__ 0 0 0 0 0 195617 14556941 261055 11629 6493 LAMC2 CSF CSF 9 0.3 However based on several previous studies showing that the CSF glutamate levels are increased in MS patients 2 and that 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 195618 14556941 261059 8791 4573 GRIA3 GLUR3 GluR3 12 1.6 found high expression of the glutamate ion channel receptor (GluR3) GluR3 on normal human T-cells human T leukemia cells and mouse 14 JUMiner_v2.2 1 0 0 2 4573 TotalCon:2<>4573|GRIA3|2892|Complete__4595|GRM3|2913|Complete__<>AvaiableGeneRif=2<>BEST:4573|GRIA3|0.000554538054538055<>ScoreDetail__4573|GRIA3|0.000554538054538055__4595|GRM3|0.000347042964492629__ 0 0 0 0 0 196768 14597108 262716 20996 11179 SOD1 ALS ALS 17 1.4 inflammation contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196769 14597108 262717 3758 10618 CCL2 MCP-1 MCP-1 2 2.8 Monocyte-chemoattractant protein (MCP-1) MCP-1 might play an important role in microglial recruitment 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196770 14597108 262718 3758 10618 CCL2 MCP-1 MCP-1 2 2.8 We studied MCP-1 levels in sera and cerebrospinal fluid of 29 ALS patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196771 14597108 262718 20996 11179 SOD1 ALS ALS 11 1.4 studied MCP-1 levels in sera and cerebrospinal fluid of 29 ALS patients and compared the results with 11 control patients with 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196772 14597108 262719 3758 10618 CCL2 MCP-1 MCP-1 1 2.8 The MCP-1 level was determined using enzyme-linked immunosorbent assays (ELISA) ELISA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196773 14597108 262720 3758 10618 CCL2 MCP-1 MCP-1 6 2.8 A significant increase in cerebrospinal fluid MCP-1 level but not serum level was seen in the patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196774 14597108 262720 20996 11179 SOD1 ALS ALS 18 1.4 but not serum level was seen in the patients with ALS compared to the control subjects 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196775 14597108 262721 3758 10618 CCL2 MCP-1 MCP-1 6 2.8 These results suggest that cerebrospinal fluid MCP-1 activity may be a sensitive marker for neuroinflammation in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196776 14597108 262721 20996 11179 SOD1 ALS ALS 16 1.4 MCP-1 activity may be a sensitive marker for neuroinflammation in ALS useful for monitoring treatment trials in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196777 14597108 262721 20996 11179 SOD1 ALS ALS 23 1.4 for neuroinflammation in ALS useful for monitoring treatment trials in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196778 14597108 262725 20996 11179 SOD1 ALS ALS 3 1.4 Amyotrophic lateral sclerosis (ALS) ALS is a progressive fatal neurodegenerative disorder that primarily affects motor 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196779 14597108 262726 20996 11179 SOD1 ALS ALS 3 1.4 The cause of ALS is not completely understood but accumulating evidence indicates that inflammatory 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196780 14597108 262727 20996 11179 SOD1 SOD1 SOD1 38 1.4 Cu/Zn Cu Zn form of the superoxide dismutase gene (SOD1), SOD1 an animal model of ALS Alexianu et al. 2001 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196781 14597108 262727 20996 11179 SOD1 ALS ALS 43 1.4 the superoxide dismutase gene (SOD1), SOD1 an animal model of ALS Alexianu et al. 2001 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196782 14597108 262728 20996 11179 SOD1 ALS ALS 17 1.4 mortem in cerebral cortex and spinal cord of patients with ALS Kawamata et al. 1992 and Troost et al. 1990 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196783 14597108 262729 20996 11179 SOD1 ALS ALS 58 1.4 been demonstrated in the cerebrospinal fluid and spinal cord of ALS patients (for for review see McGeer and McGeer 2002 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196784 14597108 262730 20996 11179 SOD1 ALS ALS 31 1.4 is neuroprotective in mutant superoxide dismutase transgenic mouse models of ALS Kriz et al. 2002 Van Den Bosch et al. 2002 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196785 14597108 262733 3758 10618 CCL2 MCP-1 MCP-1 4 2.8 Especially monocyte chemoattractant protein-1 (MCP-1) MCP-1 Maghazachi et al. 1994 may be a key trigger for 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196786 14597108 262734 3758 10618 CCL2 MCP-1 MCP-1 0 2.8 MCP-1 was found immunohistochemically in mature senile plaques and reactive microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196787 14597108 262735 3758 10618 CCL2 MCP-1 MCP-1 2 2.8 Changes in MCP-1 in living patients with ALS have not been studied however 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196788 14597108 262735 20996 11179 SOD1 ALS ALS 7 1.4 Changes in MCP-1 in living patients with ALS have not been studied however its evaluation might aid in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196789 14597108 262736 20996 11179 SOD1 ALS ALS 18 1.4 might furthermore offer a possible treatment option for patients with ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196790 14597108 262737 3758 10618 CCL2 MCP-1 MCP-1 6 2.8 Therefore the present study compares the MCP-1 level in CSF and serum of patients with ALS with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196791 14597108 262737 20996 11179 SOD1 ALS ALS 15 1.4 the MCP-1 level in CSF and serum of patients with ALS with that in controls 2 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196792 14597108 262737 11629 6493 LAMC2 CSF CSF 9 0.0 Therefore the present study compares the MCP-1 level in CSF and serum of patients with ALS with that in controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196793 14597108 262740 20996 11179 SOD1 ALS ALS 9 1.4 Experimental and control groups were matched for age 29 ALS patients (mean mean age 61.6_amp_#xb1 12.5 years and 11 individuals 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196794 14597108 262741 20996 11179 SOD1 ALS ALS 1 1.4 All ALS patients had been diagnosed with definite or probable ALS in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196795 14597108 262741 20996 11179 SOD1 ALS ALS 10 1.4 All ALS patients had been diagnosed with definite or probable ALS in accordance with the revised El Escorial criteria Brooks et 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196796 14597108 262742 20996 11179 SOD1 ALS ALS 3 1.4 Seven of the ALS patients had predominant bulbar signs and 22 had only spinal 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196797 14597108 262744 11629 6493 LAMC2 CSF CSF 17 0.0 been given to patients with tension headaches before blood and CSF sampling 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196798 14597108 262746 11629 6493 LAMC2 CSF CSF 0 0.0 CSF/serum CSF serum preparation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196799 14597108 262747 11629 6493 LAMC2 CSF CSF 0 0.0 CSF and serum samples of patients and controls were obtained with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196800 14597108 262747 11629 6493 LAMC2 CSF CSF 23 0.0 as part of the diagnostic evaluation and stored in the CSF banks of the Department of Neurology MHH Hannover and the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196801 14597108 262748 20996 11179 SOD1 ALS ALS 17 1.4 the CSF were within normal range in both patients with ALS and controls 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196802 14597108 262748 11629 6493 LAMC2 CSF CSF 8 0.0 Cells counts and the protein concentration in the CSF were within normal range in both patients with ALS and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196803 14597108 262749 11629 6493 LAMC2 CSF CSF 0 0.0 CSF samples were centrifuged immediately after lumbar puncture at 250_amp_#xd7 g 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196804 14597108 262751 3758 10618 CCL2 MCP-1 MCP-1 0 2.8 MCP-1 levels in serum and CSF samples were quantified by ELISA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196805 14597108 262751 11629 6493 LAMC2 CSF CSF 5 0.0 MCP-1 levels in serum and CSF samples were quantified by ELISA (Quantikine Quantikine R_amp_#x26 D Systems 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196806 14597108 262751 12473 20867 MCHR2 SLT SLT 33 0.0 of 450 nm (reference reference wavelength 550 nm with a SLT Reader 340 ATTC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196807 14597108 262756 3758 10618 CCL2 MCP-1 MCP-1 8 2.8 The Mann_amp_#x2013 Whitney U -test was used to compare MCP-1 levels in CSF and serum in ALS patients with controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196808 14597108 262756 20996 11179 SOD1 ALS ALS 15 1.4 used to compare MCP-1 levels in CSF and serum in ALS patients with controls 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196809 14597108 262756 11629 6493 LAMC2 CSF CSF 11 0.0 Whitney U -test was used to compare MCP-1 levels in CSF and serum in ALS patients with controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196810 14597108 262759 3758 10618 CCL2 MCP-1 MCP-1 19 2.8 relationship between age at time of lumbar puncture and intrathecal MCP-1 levels 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196811 14597108 262761 3758 10618 CCL2 MCP-1 MCP-1 4 2.8 The CSF concentration of MCP-1 was significantly ( p _amp_#x3c 0.001 higher in ALS patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196812 14597108 262761 20996 11179 SOD1 ALS ALS 12 1.4 of MCP-1 was significantly ( p _amp_#x3c 0.001 higher in ALS patients (570.5_amp_#xb1;199.9 570.5_amp_#xb1 199.9 pg/ml) pg ml as compared to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196813 14597108 262761 11629 6493 LAMC2 CSF CSF 1 0.0 The CSF concentration of MCP-1 was significantly ( p _amp_#x3c 0.001 higher 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196814 14597108 262762 20996 11179 SOD1 ALS ALS 9 1.4 Although an overlap of values was seen among the ALS group MCP-1 values of only 8 patients of 29 were 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196815 14597108 262762 3758 10618 CCL2 MCP-1 MCP-1 11 2.8 an overlap of values was seen among the ALS group MCP-1 values of only 8 patients of 29 were lower than 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196816 14597108 262763 3758 10618 CCL2 MCP-1 MCP-1 1 2.8 Furthermore MCP-1 levels in ALS patients (570.5_amp_#xb1;199.9 570.5_amp_#xb1 199.9 pg/ml) pg ml 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196817 14597108 262763 20996 11179 SOD1 ALS ALS 4 1.4 Furthermore MCP-1 levels in ALS patients (570.5_amp_#xb1;199.9 570.5_amp_#xb1 199.9 pg/ml) pg ml were substantially higher 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196818 14597108 262763 11629 6493 LAMC2 CSF CSF 13 0.0 570.5_amp_#xb1 199.9 pg/ml) pg ml were substantially higher in the CSF ( p _amp_#x3c 0.001 than in the serum (191.6_amp_#xb1;104.9 191.6_amp_#xb1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196819 14597108 262764 20996 11179 SOD1 ALS ALS 17 1.4 expression in the serum or CSF of patients with definite ALS compared with patients with probable ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196820 14597108 262764 20996 11179 SOD1 ALS ALS 23 1.4 of patients with definite ALS compared with patients with probable ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196821 14597108 262764 11629 6493 LAMC2 CSF CSF 12 0.0 no differential pattern of chemokine expression in the serum or CSF of patients with definite ALS compared with patients with probable 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196822 14597108 262765 3758 10618 CCL2 MCP-1 MCP-1 22 2.8 onset of symptoms nor of duration of the disease on MCP-1 levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196823 14597108 262766 3758 10618 CCL2 MCP-1 MCP-1 17 2.8 relationship between age at time of lumbar puncture and intrathecal MCP-1 level in ALS patients ( r =0.045 Fig 1a or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196824 14597108 262766 20996 11179 SOD1 ALS ALS 20 1.4 at time of lumbar puncture and intrathecal MCP-1 level in ALS patients ( r =0.045 Fig 1a or control patients ( 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196825 14597108 262768 20996 11179 SOD1 ALS ALS 24 1.4 as well as in the spinal cord of patients with ALS Kawamata et al. 1992 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196826 14597108 262770 20996 11179 SOD1 ALS ALS 16 1.4 the recruitment of microglial cells into the spinal cord of ALS patients have remained elusive so far 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196827 14597108 262771 3758 10618 CCL2 MCP-1 MCP-1 7 2.8 This is the first study demonstrating that MCP-1 inflammatory signalling might mediate recruitment of myelomonocytic cells to areas 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196828 14597108 262771 20996 11179 SOD1 ALS ALS 21 1.4 mediate recruitment of myelomonocytic cells to areas of neurodegeneration in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196829 14597108 262772 3758 10618 CCL2 MCP-1 MCP-1 13 2.8 provide in vivo evidence for elevated cerebrospinal fluid levels of MCP-1 in ALS patients providing further evidence for the hypothesis that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196830 14597108 262772 20996 11179 SOD1 ALS ALS 15 1.4 vivo evidence for elevated cerebrospinal fluid levels of MCP-1 in ALS patients providing further evidence for the hypothesis that inflammatory processes 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196831 14597108 262772 20996 11179 SOD1 ALS ALS 30 1.4 for the hypothesis that inflammatory processes contribute to neurodegeneration in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196832 14597108 262773 3758 10618 CCL2 MCP-1 MCP-1 4 2.8 The higher levels of MCP-1 in the CSF than in paired serum samples in patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196833 14597108 262773 20996 11179 SOD1 ALS ALS 16 1.4 the CSF than in paired serum samples in patients with ALS provide evidence for intrathecal synthesis of this chemokine 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196834 14597108 262773 11629 6493 LAMC2 CSF CSF 7 0.0 The higher levels of MCP-1 in the CSF than in paired serum samples in patients with ALS provide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196835 14597108 262774 3758 10618 CCL2 MCP-1 MCP-1 24 2.8 activation of astrocytes and microglial cells induces a release of MCP-1 a chemokine produced by both glial cell types Hayashi et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196836 14597108 262775 3758 10618 CCL2 MCP-1 MCP-1 1 2.8 Since MCP-1 is a potent activator of macrophage function and specifically attracts 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196837 14597108 262776 20996 11179 SOD1 ALS ALS 8 1.4 Neuropathological studies show that in animal models of ALS glial reactions even precede neuronal loss in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196838 14597108 262776 20996 11179 SOD1 ALS ALS 16 1.4 models of ALS glial reactions even precede neuronal loss in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196839 14597108 262777 3758 10618 CCL2 MCP-1 MCP-1 5 2.8 Therefore one might speculate that MCP-1 might further increase during the course of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196840 14597108 262777 20996 11179 SOD1 ALS ALS 13 1.4 speculate that MCP-1 might further increase during the course of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196841 14597108 262778 3758 10618 CCL2 MCP-1 MCP-1 3 2.8 Repetitive measurement of MCP-1 may be a useful laboratory marker to follow-up patients participating 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196842 14597108 262779 3758 10618 CCL2 MCP-1 MCP-1 14 2.8 between clinical impairment/progression impairment progression of the disease and CSF MCP-1 levels a larger sample size may be needed to address 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196843 14597108 262779 11629 6493 LAMC2 CSF CSF 13 0.2 correlation between clinical impairment/progression impairment progression of the disease and CSF MCP-1 levels a larger sample size may be needed to 5 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 196844 14597108 262780 20996 11179 SOD1 ALS ALS 19 1.4 explore the potential of immunotherapies specifically targeting MCP-1-dependant mechanisms in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196845 14597108 262780 3892 6953 CD46 MCP MCP-1-dependant 16 0.0 be interesting to explore the potential of immunotherapies specifically targeting MCP-1-dependant mechanisms in ALS 11 JUMiner_v2.2 1 0 0 2 6953 TotalCon:3<>6953|CD46|4179|Complete__1474|CAPG|822|Complete__32018|C1orf132|388732|No_GeneRif__<>AvaiableGeneRif=2<>BEST:6953|CD46|0.000506737674493666<>ScoreDetail__6953|CD46|0.000506737674493666__1474|CAPG|0.000485731633272617__ 0 0 0 0 0 196846 14597108 262782 3758 10618 CCL2 MCP-1 MCP-1 6 2.8 In experimental autoimmune encephalomyelitis absence of MCP-1 in mice leads to decreased local macrophage recruitment and antigen-specific 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196847 14597108 262783 3758 10618 CCL2 MCP-1 MCP-1 11 2.8 note is that bindarit an indazolic derivative able to inhibit MCP-1 is able to ameliorate adjuvant arthritis in rats Guglielmotti et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196848 14597108 262784 3758 10618 CCL2 MCP-1 MCP-1 5 2.8 The present data suggest that MCP-1 levels in CSF may be an appropriate surrogate marker in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196849 14597108 262784 20996 11179 SOD1 ALS ALS 24 1.4 marker in the diagnosis or in treatment of patients with ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196850 14597108 262784 11629 6493 LAMC2 CSF CSF 8 0.0 The present data suggest that MCP-1 levels in CSF may be an appropriate surrogate marker in the diagnosis or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196851 14597108 262785 3758 10618 CCL2 MCP-1 MCP-1 12 2.8 worthwhile to examine the prognostic value of CSF/plasma CSF plasma MCP-1 ratios in ALS patients who are followed longitudinally which should 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196852 14597108 262785 20996 11179 SOD1 ALS ALS 15 1.4 the prognostic value of CSF/plasma CSF plasma MCP-1 ratios in ALS patients who are followed longitudinally which should be done in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 196853 14597108 262785 11629 6493 LAMC2 CSF CSF 11 0.2 would be worthwhile to examine the prognostic value of CSF/plasma CSF plasma MCP-1 ratios in ALS patients who are followed longitudinally 5 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 196854 14597108 262787 3758 10618 CCL2 MCP-1 MCP-1 11 2.8 between age at the time of lumbar puncture and intrathecal MCP-1 levels in ALS patients (a) a and control patients (b) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 196855 14597108 262787 20996 11179 SOD1 ALS ALS 14 1.4 the time of lumbar puncture and intrathecal MCP-1 levels in ALS patients (a) a and control patients (b) b 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00087402263009945<>ScoreDetail__5468|IGFALS|0.00087402263009945__11179|SOD1|0.000743974127739445__ 0 0 0 0 0 186758 14642384 249791 22000 11730 TERT TERT tert 8 0.0 FDNB GSH GSSG iodoacetic acid (IA), IA N-ethylmaleimide (NEM), NEM tert -butyl hydroperoxide (t-BOOH), t-BOOH and trichloroacetic acid (TCA) TCA were 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 186759 14642384 249798 22000 11730 TERT TERT tert 3 0.0 Then 1 mM tert -butyl hydroperoxide (t-BOOH) t-BOOH treatment was performed on heparinized blood 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 186760 14642384 249836 9038 4827 HBB hemoglobin hemoglobin 19 1.0 to avoid GSH oxidation during acidification in the presence of hemoglobin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 186761 14642384 249888 16561 8947 PI3 ESI ESI-MS_amp_#x2014 10 0.0 disulfide HPLC_amp_#x2014 high-pressure liquid chromatography IA_amp_#x2014 iodoacetic acid LC/ESI-MS_amp_#x2014;liquid LC ESI-MS_amp_#x2014 liquid chromatography/electron chromatography electron spray ionization-mass spectrometry NEM_amp_#x2014 N-ethylmaleimide t-BOOH_amp_#x2014 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 186762 14642384 249888 22000 11730 TERT TERT tert 17 0.0 liquid chromatography/electron chromatography electron spray ionization-mass spectrometry NEM_amp_#x2014 N-ethylmaleimide t-BOOH_amp_#x2014 tert -butylhydroperoxide TCA_amp_#x2014 trichloroacetic acid 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 187086 14645737 250134 9947 5468 IGFALS ALS ALS 5 0.3 Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00132105505278114<>ScoreDetail__5468|IGFALS|0.000868960722975322__11179|SOD1|0.00132105505278114__ 0 0 0 0 0 187087 14645737 250135 9947 5468 IGFALS ALS ALS 16 0.3 patterns in the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00132105505278114<>ScoreDetail__5468|IGFALS|0.000868960722975322__11179|SOD1|0.00132105505278114__ 0 0 0 0 0 187088 14645737 250136 9947 5468 IGFALS ALS ALS 27 0.3 in postmortem spinal cord gray matter obtained from individuals with ALS as well as normal individuals 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00132105505278114<>ScoreDetail__5468|IGFALS|0.000868960722975322__11179|SOD1|0.00132105505278114__ 0 0 0 0 0 187089 14645737 250137 9947 5468 IGFALS ALS ALS-specific 12 0.3 (FDA) FDA and leave-one-out cross-validation (LOOCV), LOOCV we discerned an ALS-specific signature 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00132105505278114<>ScoreDetail__5468|IGFALS|0.000868960722975322__11179|SOD1|0.00132105505278114__ 0 0 0 0 0 187090 14645737 250138 9947 5468 IGFALS ALS ALS 7 0.3 Moreover it was possible to distinguish familial ALS (FALS) FALS from sporadic ALS (SALS) SALS gene expression profiles 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00132105505278114<>ScoreDetail__5468|IGFALS|0.000868960722975322__11179|SOD1|0.00132105505278114__ 0 0 0 0 0 187091 14645737 250138 9947 5468 IGFALS ALS ALS 11 0.3 was possible to distinguish familial ALS (FALS) FALS from sporadic ALS (SALS) SALS gene expression profiles 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00132105505278114<>ScoreDetail__5468|IGFALS|0.000868960722975322__11179|SOD1|0.00132105505278114__ 0 0 0 0 0 187092 14645737 250139 9947 5468 IGFALS ALS ALS 8 0.3 Characterization of the specific genes significantly altered in ALS uncovered a pro-inflammatory terminal state 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00132105505278114<>ScoreDetail__5468|IGFALS|0.000868960722975322__11179|SOD1|0.00132105505278114__ 0 0 0 0 0 187093 14645737 250141 9947 5468 IGFALS ALS ALS 26 0.3 phenotypic changes that underlie the terminal stages of neurodegeneration in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00132105505278114<>ScoreDetail__5468|IGFALS|0.000868960722975322__11179|SOD1|0.00132105505278114__ 0 0 0 0 0 188367 14661102 251394 16315 30012 PDF PDF PDF 2 0.5 Contribution in PDF 3 JUMiner_v2.2 1 2 UserEdit 0 2 30142 TotalCon:3<>30012|PDF|64146|Complete__30142|GDF15|9518|Complete__8866|PFDN1|5201|Complete__<>AvaiableGeneRif=3<>BEST:30142|GDF15|0.000422092041646415<>ScoreDetail__8866|PFDN1|0__30142|GDF15|0.000422092041646415__30012|PDF|0.000368188512518409__ 1 1 0 0 0 190248 14720207 253624 20996 11179 SOD1 ALS ALS 14 1.4 both inflammation and mitochondrial dysfunction in amyotrophic lateral sclerosis (ALS) ALS pathogenesis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011702678254673<>ScoreDetail__5468|IGFALS|0.000437082040298964__11179|SOD1|0.0011702678254673__ 0 0 0 0 0 190249 14720207 253625 17610 9605 PTGS2 COX-2 COX-2 8 1.3 We investigated the therapeutic effects of cyclooxygenase 2 (COX-2) COX-2 inhibitors both alone and in combination with creatine in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190250 14720207 253625 20996 11179 SOD1 ALS ALS 24 1.4 combination with creatine in the G93A transgenic mouse model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011702678254673<>ScoreDetail__5468|IGFALS|0.000437082040298964__11179|SOD1|0.0011702678254673__ 0 0 0 0 0 190251 14720207 253627 17610 9605 PTGS2 COX-2 COX-2 3 1.3 The administration of COX-2 inhibitors significantly reduced prostaglandin E2 levels at 110 days of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190252 14720207 253628 17610 9605 PTGS2 COX-2 COX-2 5 1.3 The combination of creatine with COX-2 inhibitors produced additive neuroprotective effects and extended survival by approximately 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190253 14720207 253629 17610 9605 PTGS2 COX-2 COX-2 1 1.3 The COX-2 inhibitors significantly protected against depletion of anterior horn motor neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190254 14720207 253629 17610 9605 PTGS2 COX-2 COX-2 15 1.3 against depletion of anterior horn motor neurons and creatine with COX-2 inhibitors showed greater protection than COX-2 inhibitors alone 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190255 14720207 253629 17610 9605 PTGS2 COX-2 COX-2 21 1.3 neurons and creatine with COX-2 inhibitors showed greater protection than COX-2 inhibitors alone 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190256 14720207 253630 20996 11179 SOD1 ALS ALS 20 1.4 mechanisms may be a useful strategy in the treatment of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011702678254673<>ScoreDetail__5468|IGFALS|0.000437082040298964__11179|SOD1|0.0011702678254673__ 0 0 0 0 0 190795 14739060 254283 6981 22140 FAM20C RNS RNS 19 0.3 reactive oxygen species (ROS) ROS and reactive nitrogen species (RNS) RNS 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190796 14739060 254283 18723 10261 ROS1 ROS ROS 14 0.0 as accountable for redox regulation involving reactive oxygen species (ROS) ROS and reactive nitrogen species (RNS) RNS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190797 14739060 254289 18723 10261 ROS1 ROS ROS 7 0.0 ATP synthesis is responsible for most of ROS and notably the first produced superoxide anion ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190798 14739060 254290 20996 11179 SOD1 ALS ALS 35 1.3 Parkinson_amp_#x2019 s disease (PD) PD and amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160093311530149<>ScoreDetail__5468|IGFALS|0.000534659909805198__11179|SOD1|0.00160093311530149__ 0 0 0 0 0 190799 14739060 254290 18723 10261 ROS1 ROS ROS 10 0.0 Mitochondrial dysfunction i.e cell energy impairment apoptosis and overproduction of ROS is a final common pathogenic mechanism in aging and in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190800 14739060 254291 6981 22140 FAM20C RNS RNS 5 0.3 Nitric oxide (NO NO an RNS which can be produced by three isoforms of NO-synthase in 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190801 14739060 254292 20996 11179 SOD1 ALS ALS 9 1.3 The research on the genetics of inherited forms notably ALS AD PD has improved our understanding of the pathobiology of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160093311530149<>ScoreDetail__5468|IGFALS|0.000534659909805198__11179|SOD1|0.00160093311530149__ 0 0 0 0 0 190802 14739060 254293 6981 22140 FAM20C RNS RNS 2 0.3 ROS and RNS i.e oxidative stress are not the origin of neuronal death 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190803 14739060 254293 18723 10261 ROS1 ROS ROS 0 0.1 ROS and RNS i.e oxidative stress are not the origin of 6 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 190804 14739060 254311 18723 10261 ROS1 ROS ROS 14 0.0 is responsible for most of the reactive oxygen species (ROS) ROS and notably the first produced superoxide anion ( in human 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190805 14739060 254312 18723 10261 ROS1 ROS ROS 14 0.0 1_amp_#x2013 2% of the O 2 consumed is converted to ROS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190806 14739060 254313 6981 22140 FAM20C RNS RNS 11 0.3 is nitric oxide (NO NO a reactive nitrogen species (RNS) RNS 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190807 14739060 254314 14533 7872 NOS1 nNOS nNOS 36 1.9 account for NO production and include neuronal NO synthase (nNOS; nNOS type I inducible NO synthase (iNOS; iNOS typeII which is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190808 14739060 254314 14535 7873 NOS2A iNOS iNOS 42 1.9 NO synthase (nNOS; nNOS type I inducible NO synthase (iNOS; iNOS typeII which is produced in very large amounts by activated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190809 14739060 254314 14538 7876 NOS3 eNOS eNOS 59 1.9 by activated microglia (macrophages), macrophages and endothelial NO synthase (eNOS; eNOS type III In the CNS nNOS whose expression is regulated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190810 14739060 254314 14533 7872 NOS1 nNOS nNOS 65 1.9 endothelial NO synthase (eNOS; eNOS type III In the CNS nNOS whose expression is regulated by both physiological and pathophysiological stimuli 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190811 14739060 254315 6981 22140 FAM20C RNS RNS 15 0.3 peroxynitrite (ONOO ONOO _amp_#x2013 _amp_#x2013 which is the most reactive RNS 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190812 14739060 254316 6981 22140 FAM20C RNS RNS 2 0.3 ROS and RNS are the cause of oxidative stress in nervous system 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190813 14739060 254316 18723 10261 ROS1 ROS ROS 0 0.1 ROS and RNS are the cause of oxidative stress in nervous 6 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 190814 14739060 254317 14535 7873 NOS2A iNOS iNOS 15 1.9 in pathologic conditions especially NO coming from activated microglia (iNOS) iNOS or and from endothelial cells (eNOS) eNOS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190815 14739060 254317 14538 7876 NOS3 eNOS eNOS 21 1.9 activated microglia (iNOS) iNOS or and from endothelial cells (eNOS) eNOS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190816 14739060 254318 18723 10261 ROS1 ROS ROS 4 0.0 The main sources of ROS in inflammatory process are both damaged mitochondria and activated microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190817 14739060 254319 6981 22140 FAM20C RNS RNS 15 0.3 as an imbalance between generation and elimination of ROS and RNS 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190818 14739060 254319 18723 10261 ROS1 ROS ROS 13 0.1 is described as an imbalance between generation and elimination of ROS and RNS 6 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 190819 14739060 254321 12337 6871 MAPK1 MAP MAP 28 0.3 for neurons astrocytes and microglia such as mitogene-activated protein (MAP) MAP kinase cascade activation ion transport calcium mobilization and apoptosis program 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190820 14739060 254321 18723 10261 ROS1 ROS ROS 8 0.0 It is now recognized that redox regulation involving ROS is key to the modulation of critical cellular functions notably 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190821 14739060 254330 6981 22140 FAM20C RNS RNS 2 0.3 ROS and RNS are involved in both apoptosis and excitotoxicity 27 and 28 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190822 14739060 254330 18723 10261 ROS1 ROS ROS 0 0.1 ROS and RNS are involved in both apoptosis and excitotoxicity 27 6 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 190823 14739060 254345 14533 7872 NOS1 nNOS nNOS 17 1.9 series of enzymes including protein kinase C proteases phosphatases phospholipases nNOS and xanthine oxidase 32 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190824 14739060 254346 6981 22140 FAM20C RNS RNS 10 0.3 The last three (phospholipase phospholipase A 2 produce ROS and RNS by triggering acide arachidonic cascade 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190825 14739060 254346 18723 10261 ROS1 ROS ROS 8 0.1 The last three (phospholipase phospholipase A 2 produce ROS and RNS by triggering acide arachidonic cascade 6 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 190826 14739060 254361 6981 22140 FAM20C RNS RNS 13 0.3 result in overproduction of proteolytic enzymes lipid peroxidation ROS and RNS formation 33 and in triggering programmed cell death i.e apoptosis 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190827 14739060 254361 18723 10261 ROS1 ROS ROS 11 0.1 intracellular responses result in overproduction of proteolytic enzymes lipid peroxidation ROS and RNS formation 33 and in triggering programmed cell death 6 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 190828 14739060 254366 6981 22140 FAM20C RNS RNS 32 0.3 as that triggered by excitotoxicity _amp_#x2022 elevated levels of ROS_amp_#x2013 RNS 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190829 14739060 254366 1576 990 BCL2 Bcl2 Bcl2 14 0.0 the release of apoptogenic mitochondrial mediators _amp_#x2022 Pro-apoptotic members of Bcl2 family _amp_#x2022 elevated levels of intra-cellular calcium such as that 1 JUMiner_v2.2 1 1 bcl2; 0 0 0 0 0 0 0 0 190830 14739060 254368 5854 21528 DIABLO SMAC Smac 31 1.3 the mitochondria into cytoplasm trigger the caspase chain _amp_#x2022 Smac/Diablo Smac Diablo binds to inhibitors of activated caspases and causes further 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190831 14739060 254369 18723 10261 ROS1 ROS ROS 4 0.0 When the level of ROS exceeds the capacity of the mitochondria and cell to detoxify 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190832 14739060 254372 864 576 APAF1 APAF1 Apaf1 6 0.3 Cytochrome c and the cytosolic factor Apaf1 activate the caspases while apoptosis-initiating factor and caspase activated DNase 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190833 14739060 254378 20996 11179 SOD1 ALS ALS 46 1.3 neurons obtained by cyclooxygenase 2_amp_#xa0 in transgenic mouse model of ALS 15 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160093311530149<>ScoreDetail__5468|IGFALS|0.000534659909805198__11179|SOD1|0.00160093311530149__ 0 0 0 0 0 190834 14739060 254380 20996 11179 SOD1 ALS ALS 36 1.3 heterozygote gene diseases for example familial amyotrophic lateral sclerosis (ALS), ALS familial Parkinson_amp_#x2019 s disease (PD), PD familial Alzheimer_amp_#x2019 s disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160093311530149<>ScoreDetail__5468|IGFALS|0.000534659909805198__11179|SOD1|0.00160093311530149__ 0 0 0 0 0 190835 14739060 254383 20996 11179 SOD1 ALS ALS 0 1.3 ALS a neurodegenerative disease characterized by the degeneration of motor neurons 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160093311530149<>ScoreDetail__5468|IGFALS|0.000534659909805198__11179|SOD1|0.00160093311530149__ 0 0 0 0 0 190836 14739060 254383 20996 11179 SOD1 SOD SOD 18 1.3 of motor neurons caused by a missense mutation of CuZn SOD (SOD1) SOD1 is an illustration of how these mechanisms can 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190837 14739060 254383 20996 11179 SOD1 SOD1 SOD1 19 2.1 neurons caused by a missense mutation of CuZn SOD (SOD1) SOD1 is an illustration of how these mechanisms can lead to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190838 14739060 254384 20996 11179 SOD1 SOD1 SOD1 7 2.1 In transgenic mice expressing the human mutant SOD1 gene syndrome develops with many features of ALS including specific 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190839 14739060 254384 20996 11179 SOD1 ALS ALS 15 1.3 human mutant SOD1 gene syndrome develops with many features of ALS including specific cell death of motor neurons progressive weakness and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160093311530149<>ScoreDetail__5468|IGFALS|0.000534659909805198__11179|SOD1|0.00160093311530149__ 0 0 0 0 0 190840 14739060 254385 20996 11179 SOD1 SOD1 SOD1 21 2.1 to compare the evolution for motor neurons degeneration in mutant SOD1 transgenic mouse with non-transgenic mouse and normal human SOD1 transgenic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190841 14739060 254385 20996 11179 SOD1 SOD1 SOD1 30 2.1 mutant SOD1 transgenic mouse with non-transgenic mouse and normal human SOD1 transgenic mouse 46 50 47 48 and 49 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190842 14739060 254387 20996 11179 SOD1 SOD1 SOD1 4 2.1 The toxicity of mutant SOD1 seems to be due to a gain of function of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190843 14739060 254389 20996 11179 SOD1 SOD1 SOD1 5 2.1 It is also conceivable mutant SOD1 denatures more quickly in vivo than the normal form and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190844 14739060 254390 20996 11179 SOD1 SOD1 SOD1 9 2.1 Oxidative stress may be involved in misfolding of mutant SOD1 to form abnormal protein aggregates found as early as 1_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190845 14739060 254391 20996 11179 SOD1 SOD1 SOD1 11 2.1 disorganization of intermediate filaments could be due also to mutant SOD1 induced toxicity as their proteins are vulnerable to oxidative damage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190846 14739060 254392 20996 11179 SOD1 ALS ALS 13 1.3 peripherin is found in neuronal inclusions in patients with sporadic ALS and in transgenic mice with SOD1 mutations 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160093311530149<>ScoreDetail__5468|IGFALS|0.000534659909805198__11179|SOD1|0.00160093311530149__ 0 0 0 0 0 190847 14739060 254392 20996 11179 SOD1 SOD1 SOD1 19 2.1 in patients with sporadic ALS and in transgenic mice with SOD1 mutations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190848 14739060 254395 20996 11179 SOD1 SOD SOD 22 1.3 of ubiquinated cytoplasmic inclusion bodies some of which contain aggregated SOD 46 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190849 14739060 254397 20996 11179 SOD1 SOD1 SOD1 4 2.1 The studies on mutant SOD1 transgenic mice 46 and 63 revealed an up-regulation of gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190850 14739060 254398 20996 11179 SOD1 ALS ALS 12 1.3 of other neurodegenerative diseases with familial and sporadic forms like ALS display numerous similitudes 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160093311530149<>ScoreDetail__5468|IGFALS|0.000534659909805198__11179|SOD1|0.00160093311530149__ 0 0 0 0 0 190851 14739060 254401 926 620 APP amyloid amyloid 11 1.0 forms missense mutation have been identified for gene encoding _amp_#x3b2 -amyloid precursor protein as well as presenilin 1 (PSEN1) PSEN1 and 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 190852 14739060 254401 17461 9508 PSEN1 PSEN1 PSEN1 19 0.9 _amp_#x3b2 -amyloid precursor protein as well as presenilin 1 (PSEN1) PSEN1 and presenilin 2 (PSEN2) PSEN2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190853 14739060 254401 17462 9509 PSEN2 PSEN2 PSEN2 23 0.9 well as presenilin 1 (PSEN1) PSEN1 and presenilin 2 (PSEN2) PSEN2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190854 14739060 254402 12369 6893 MAPT tau tau 30 1.9 gene for _amp_#x3b1 2 -macrogobulin and perhaps the gene for tau protein and other factors including environmental contributions and occurrence by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190855 14739060 254402 912 613 APOE APOE APOE 18 0.0 a complex interaction among multiple predisposing genes such as variant APOE the gene for _amp_#x3b1 2 -macrogobulin and perhaps the gene 1 JUMiner_v2.2 1 1 apoe; 0 0 0 0 0 0 0 0 190856 14739060 254403 12369 6893 MAPT tau tau 14 1.9 tangles and senile plaques are both aggregation of proteins microtubular tau protein for the former accumulation of several aggregated proteins (_amp_#x3b2;-amyloid, 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190857 14739060 254403 926 620 APP amyloid amyloid 24 1.0 for the former accumulation of several aggregated proteins (_amp_#x3b2;-amyloid, _amp_#x3b2 -amyloid especially its toxic form A_amp_#x3b2 42 APOE 43 hyperphosphorylated tau 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 190858 14739060 254403 12369 6893 MAPT tau tau 37 1.9 -amyloid especially its toxic form A_amp_#x3b2 42 APOE 43 hyperphosphorylated tau ubiquitin presenilin 1_amp_#xa0 and 2 with an inflammatory reaction around 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190859 14739060 254403 926 620 APP amyloid amyloid 50 1.0 2 with an inflammatory reaction around the deposit of _amp_#x3b2 -amyloid for the latter 38 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 190860 14739060 254403 912 613 APOE APOE APOE 32 0.0 proteins (_amp_#x3b2;-amyloid, _amp_#x3b2 -amyloid especially its toxic form A_amp_#x3b2 42 APOE 43 hyperphosphorylated tau ubiquitin presenilin 1_amp_#xa0 and 2 with an 1 JUMiner_v2.2 1 1 apoe; 0 0 0 0 0 0 0 0 190861 14739060 254417 4772 26515 COQ10A Q10 Q10 11 0.9 a controlled trial in early PD oral treatment with coenzyme Q10 has slowed the progressive deterioration 56 and in aged mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190862 14739060 254434 166 118 ACO2 aconitase aconitase 9 1.3 may prevent the formation of Fe/S Fe S in mitochondrial aconitase and in complex I 20 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190863 14739060 254448 12580 7008 MELAS MELAS MELAS 18 3.4 as mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes syndrome (MELAS) MELAS 1 JUMiner_v2.2 1 0 1 0 0 0 0 0 0 0 190864 14739060 254455 4772 26515 COQ10A Q10 Q10 12 0.9 affected sisters clinical and biochemical abnormalities improved remarkably with coenzyme Q10 supplementation 59 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190865 14739060 254464 6981 22140 FAM20C RNS RNS 15 0.3 of aging i.e progressive damage to mtDNA by ROS/RNS ROS RNS 42 and induced changes in redox state of the cell 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190866 14739060 254464 18723 10261 ROS1 ROS ROS 15 0.3 theory of aging i.e progressive damage to mtDNA by ROS/RNS ROS RNS 42 and induced changes in redox state of the 4 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 190867 14739060 254468 18723 10261 ROS1 ROS ROS 44 0.0 reflect either decreased mitochondrial biogenesis or turnover secondary to cumulative ROS inflicted mitochondrial damage 11 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190868 14739060 254479 22551 11892 TNF TNF TNF 27 0.3 amplification resulting in production of neurotoxins such as cytokine (TNF, TNF IL1 eicosanoides ROS and RNS 9 and 13 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190869 14739060 254479 6981 22140 FAM20C RNS RNS 32 0.3 neurotoxins such as cytokine (TNF, TNF IL1 eicosanoides ROS and RNS 9 and 13 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 190870 14739060 254479 10436 5991 IL1A IL1 IL1 28 0.2 resulting in production of neurotoxins such as cytokine (TNF, TNF IL1 eicosanoides ROS and RNS 9 and 13 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190871 14739060 254479 18723 10261 ROS1 ROS ROS 30 0.1 production of neurotoxins such as cytokine (TNF, TNF IL1 eicosanoides ROS and RNS 9 and 13 6 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 190872 14739060 254483 20997 11180 SOD2 MnSOD MnSOD 7 1.8 Tat protein decreases GSH and down regulate MnSOD gene expression leading to oxidative stress 16 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 190873 14739060 254490 20996 11179 SOD1 ALS ALS 3 1.3 Animal models for ALS 17 and 19 AD PD 5 and aging brain 35 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00160093311530149<>ScoreDetail__5468|IGFALS|0.000534659909805198__11179|SOD1|0.00160093311530149__ 0 0 0 0 0 180857 14960605 241507 10676 6121 IRF6 LPS LPS 15 0.3 the effects of acute and chronic administration of lipopolysaccharide (LPS), LPS a Gram-negative bacterial wall component in a genetic model of 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180858 14960605 241508 20996 11179 SOD1 SOD1 SOD1 11 3.0 expressing a mutant form of the superoxide dismutase 1 (SOD1 SOD1 linked to familial amyotrophic lateral sclerosis were challenged intraperitoneally with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180859 14960605 241508 10676 6121 IRF6 LPS LPS 30 0.3 challenged intraperitoneally with a single nontoxic or repeated injections of LPS (1 1 mg/kg) mg kg 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180860 14960605 241509 20996 11179 SOD1 SOD1 SOD1 3 3.0 At different ages SOD1 mice responded normally to acute endotoxemia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180861 14960605 241510 10676 6121 IRF6 LPS LPS 6 0.3 Remarkably only a chronic challenge with LPS in presymptomatic 6-month-old SOD1 mice exacerbated disease progression by 3 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180862 14960605 241510 20996 11179 SOD1 SOD1 SOD1 10 3.0 Remarkably only a chronic challenge with LPS in presymptomatic 6-month-old SOD1 mice exacerbated disease progression by 3 weeks and motor axon 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180863 14960605 241511 10676 6121 IRF6 LPS LPS-treated 42 0.3 cord and efferent fiber tracts of the brain from the LPS-treated SOD1 mice 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180864 14960605 241511 20996 11179 SOD1 SOD1 SOD1 43 3.0 and efferent fiber tracts of the brain from the LPS-treated SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180865 14960605 241519 20996 11179 SOD1 SOD1 SOD1 20 3.0 mice expressing a mutant form of superoxide dismutase 1 (SOD1 SOD1 linked to amyotrophic lateral sclerosis (ALS), ALS the most common 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180866 14960605 241519 20996 11179 SOD1 ALS ALS 27 1.7 dismutase 1 (SOD1 SOD1 linked to amyotrophic lateral sclerosis (ALS), ALS the most common form of human motor neuron disease (Nguyen 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180867 14960605 241519 20996 11179 SOD1 ALS ALS 45 1.7 disease (Nguyen Nguyen et al. 2001b ~20% cases of familial ALS (Rosen Rosen et al. 1993 Cudkowicz et al. 1997 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180868 14960605 241520 20996 11179 SOD1 SOD1 SOD1 1 3.0 The SOD1 protein is a cytosolic metalloenzyme catalyzing the conversion of superoxide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180869 14960605 241521 20996 11179 SOD1 SOD1 SOD1 4 3.0 Transgenic mice expressing mutant SOD1 develop motor neuron disease resembling ALS through a gain of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180870 14960605 241521 20996 11179 SOD1 ALS ALS 10 1.7 Transgenic mice expressing mutant SOD1 develop motor neuron disease resembling ALS through a gain of unidentified deleterious properties (Wong Wong et 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180871 14960605 241522 7333 11920 FAS FAS Fas 39 0.6 et al. 1998 cytoskeletal abnormalities (Wong Wong et al. 1995 Fas ligand (FasL)-mediated FasL -mediated death (Raoul Raoul et al. 2002 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000448612549811926<>ScoreDetail__11920|FAS|0.000448612549811926__3594|FASN|0.000432770186366102__ 0 0 0 0 0 180872 14960605 241522 7334 11936 FASLG FasL FasL 41 2.2 cytoskeletal abnormalities (Wong Wong et al. 1995 Fas ligand (FasL)-mediated FasL -mediated death (Raoul Raoul et al. 2002 and deregulation of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180873 14960605 241522 4039 1774 CDK5 CDK5 Cdk5 51 1.9 -mediated death (Raoul Raoul et al. 2002 and deregulation of Cdk5 (cyclin-dependent cyclin-dependent kinase 5 (Nguyen Nguyen et al. 2001a 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180874 14960605 241523 20996 11179 SOD1 SOD1 SOD1 6 3.0 Despite these findings the toxicity of SOD1 mutants linked to human ALS remains poorly understood 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180875 14960605 241523 20996 11179 SOD1 ALS ALS 11 1.7 these findings the toxicity of SOD1 mutants linked to human ALS remains poorly understood 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180876 14960605 241524 20996 11179 SOD1 SOD1 SOD1 0 3.0 SOD1 is a ubiquitously expressed protein and therefore it is possible 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180877 14960605 241524 20996 11179 SOD1 ALS ALS 21 1.7 that cells other than motor neurons play a role in ALS (Clement Clement et al. 2003 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180878 14960605 241525 20996 11179 SOD1 SOD1 SOD1 6 3.0 Indeed a restricted expression of mutant SOD1 to neurons in transgenic mice was not sufficient to provoke 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180879 14960605 241526 20996 11179 SOD1 SOD1 SOD1 7 3.0 Neither did the selective expression of mutant SOD1 in astrocytes provoke pathology despite astrocytosis (Gong Gong et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180880 14960605 241527 20996 11179 SOD1 ALS ALS 24 1.7 processes and activation of microglia and other immune cells in ALS patients and mice (Bruijn Bruijn et al. 1997 Nguyen et 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180881 14960605 241528 20996 11179 SOD1 ALS ALS 14 1.7 compounds has recently conferred protection in models of neurodegeneration including ALS (Drachman Drachman and Rothstein 2000 Kriz et al. 2002 Schenk 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180882 14960605 241531 20996 11179 SOD1 SOD1 SOD1 10 3.0 In the present study we triggered the innate immunity of SOD1 mice with systemic administration of lipopolysaccharide (LPS), LPS a potent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180883 14960605 241531 10676 6121 IRF6 LPS LPS 17 0.3 immunity of SOD1 mice with systemic administration of lipopolysaccharide (LPS), LPS a potent activator of microglia 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180884 14960605 241532 10676 6121 IRF6 LPS LPS 11 0.3 results demonstrate that chronic activation of innate immunity by systemic LPS is noxious to motor neurons bearing SOD1 linked to ALS 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180885 14960605 241532 20996 11179 SOD1 SOD1 SOD1 18 3.0 immunity by systemic LPS is noxious to motor neurons bearing SOD1 linked to ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180886 14960605 241532 20996 11179 SOD1 ALS ALS 21 1.7 LPS is noxious to motor neurons bearing SOD1 linked to ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180887 14960605 241534 20996 11179 SOD1 SOD1 SOD1 2 3.0 Generation of SOD1 mice and protocol for LPS injection 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180888 14960605 241534 10676 6121 IRF6 LPS LPS 7 0.3 Generation of SOD1 mice and protocol for LPS injection 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180889 14960605 241535 20996 11179 SOD1 SOD1 SOD1 3 3.0 The inbred C57BL/6 C57BL 6 SOD1 mice (line line 29 used in this study have a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180890 14960605 241536 20996 11179 SOD1 SOD1 SOD1 1 3.0 C57BL/6 C57BL 6 SOD1 mice (line line 42 exhibit a life span of 5-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180891 14960605 241538 20996 11179 SOD1 SOD1 SOD1 1 3.0 The SOD1 mice were housed at room temperature (21degreeC) 21degreeC and in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180892 14960605 241539 10676 6121 IRF6 LPS LPS 9 0.3 To avoid any potential interference with the effects of LPS mice were kept in a pathogen-free facility 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180893 14960605 241540 20996 11179 SOD1 SOD1 SOD1 15 3.0 immune response in the CNS presymptomatic 3- 6- and 9-month-old SOD1 mice received a single intraperitoneal injection of LPS (1 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180894 14960605 241540 10676 6121 IRF6 LPS LPS 23 0.3 and 9-month-old SOD1 mice received a single intraperitoneal injection of LPS (1 1 mg/kg mg kg of body weight from Escherichia 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180895 14960605 241545 20996 11179 SOD1 SOD1 SOD1 5 3.0 Another group of presymptomatic 6-month-old SOD1 mice received intraperitoneal LPS or vehicle injections once every 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180896 14960605 241545 10676 6121 IRF6 LPS LPS 9 0.3 Another group of presymptomatic 6-month-old SOD1 mice received intraperitoneal LPS or vehicle injections once every 2 weeks for a duration 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180897 14960605 241546 10676 6121 IRF6 LPS LPS-treated 9 0.3 Around month 9 (42-43 42-43 weeks of age the chronically LPS-treated SOD1 mice exhibited the first signs of paralysis and the 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180898 14960605 241546 20996 11179 SOD1 SOD1 SOD1 10 3.0 month 9 (42-43 42-43 weeks of age the chronically LPS-treated SOD1 mice exhibited the first signs of paralysis and the injections 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180899 14960605 241549 20996 11179 SOD1 SOD1 SOD1 6 3.0 At the same time Veh-SOD1 or SOD1 mice that did not show signs of paralysis were killed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180900 14960605 241550 20996 11179 SOD1 SOD1 SOD1 5 3.0 Some of the Veh-SOD1 or SOD1 were left until they exhibited the paralytic phenotype (3-5 3-5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180901 14960605 241551 20996 11179 SOD1 SOD1 SOD1 7 3.0 Thus the analysis of the Veh-SOD1 and SOD1 mice was performed strictly before the onset and not at 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180902 14960605 241561 20996 11179 SOD1 ALS ALS 26 1.7 or necrosis is the dominant form of cell death in ALS (Migheli Migheli et al. 1999 Pasinelli et al. 2000 Vukosavic 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180903 14960605 241562 20996 11179 SOD1 SOD1 SOD1 0 3.0 SOD1 mice exhibited a normal innate immune response after an acute 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180904 14960605 241562 10676 6121 IRF6 LPS LPS 12 0.3 exhibited a normal innate immune response after an acute systemic LPS injection 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180905 14960605 241563 10676 6121 IRF6 LPS LPS 3 0.3 A single systemic LPS injection caused a robust increase in the expression of Toll-like 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180906 14960605 241563 20996 11179 SOD1 SOD1 SOD1 29 3.0 and spinal cord of both normal wild-type (WT)] WT and SOD1 mice ( Fig 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180907 14960605 241565 14352 7794 NFKB1 NF-kappaB NF-kappaB 39 0.6 et al. 2001 kappaB alpha inhibitory protein of nuclear factor-kappaB NF-kappaB (index index of NF-kappaB activity tumor necrosis factor-alpha TNF-alpha and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180908 14960605 241565 14352 7794 NFKB1 NF-kappaB NF-kappaB 43 0.6 alpha inhibitory protein of nuclear factor-kappaB NF-kappaB (index index of NF-kappaB activity tumor necrosis factor-alpha TNF-alpha and CD14 (data data not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180909 14960605 241565 22551 11892 TNF TNF-alpha TNF-alpha 50 1.7 factor-kappaB NF-kappaB (index index of NF-kappaB activity tumor necrosis factor-alpha TNF-alpha and CD14 (data data not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180910 14960605 241565 14211 7685 NDUFA2 CD14 CD14 53 1.0 (index index of NF-kappaB activity tumor necrosis factor-alpha TNF-alpha and CD14 (data data not shown 1 JUMiner_v2.2 1 0 0 2 7685 TotalCon:2<>1628|CD14|929|Complete__7685|NDUFA2|4695|Complete__<>AvaiableGeneRif=2<>BEST:7685|NDUFA2|0.000470291351227346<>ScoreDetail__7685|NDUFA2|0.000470291351227346__1628|CD14|0.000414718472071218__ 0 0 0 0 0 180911 14960605 241566 10676 6121 IRF6 LPS LPS 26 0.3 control of the innate immune response in the CNS after LPS administration 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180912 14960605 241567 22217 11848 TLR2 TLR2 TLR2 9 5.1 Activation of innate immunity featured by the expression of TLR2 and several other inflammatory genes takes place in transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180913 14960605 241567 20996 11179 SOD1 SOD1 SOD1 21 3.0 several other inflammatory genes takes place in transgenic mice expressing SOD1 linked to ALS (Nguyen Nguyen et al. 2001b 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180914 14960605 241567 20996 11179 SOD1 ALS ALS 24 1.7 genes takes place in transgenic mice expressing SOD1 linked to ALS (Nguyen Nguyen et al. 2001b 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180915 14960605 241568 10676 6121 IRF6 LPS LPS 7 0.3 The results presented here demonstrate that repeated LPS injections exacerbated the pathogenesis and neuronal death processes of ALS 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180916 14960605 241568 20996 11179 SOD1 ALS ALS 17 1.7 LPS injections exacerbated the pathogenesis and neuronal death processes of ALS caused by SOD1 mutation 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180917 14960605 241568 20996 11179 SOD1 SOD1 SOD1 20 3.0 the pathogenesis and neuronal death processes of ALS caused by SOD1 mutation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180918 14960605 241569 20996 11179 SOD1 SOD1 SOD1 1 3.0 Although SOD1 mice responded normally to an acute systemic injection of LPS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180919 14960605 241569 10676 6121 IRF6 LPS LPS 11 0.3 SOD1 mice responded normally to an acute systemic injection of LPS chronic stimulation of innate immune response with the bacterial cell 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180920 14960605 241569 22217 11848 TLR2 TLR2 TLR2 29 5.1 the bacterial cell wall component led to sustained induction of TLR2 receptor strictly within parenchymal microglial cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180921 14960605 241570 22217 11848 TLR2 TLR2 TLR2 3 5.1 This upregulation of TLR2 was not accompanied by enhanced expression of both endogenous and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180922 14960605 241570 20996 11179 SOD1 SOD1 SOD1 15 3.0 not accompanied by enhanced expression of both endogenous and transgene SOD1 ( Fig 6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180923 14960605 241571 22217 11848 TLR2 TLR2 TLR2 5 5.1 Most importantly the degree of TLR2 induction correlated perfectly with degenerating motor neurons and motor axons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180924 14960605 241572 10676 6121 IRF6 LPS LPS-treated 5 0.3 As a consequence the chronically LPS-treated SOD1 mice exhibited accelerated disease progression motor axon degeneration and 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180925 14960605 241572 20996 11179 SOD1 SOD1 SOD1 6 3.0 As a consequence the chronically LPS-treated SOD1 mice exhibited accelerated disease progression motor axon degeneration and a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180926 14960605 241573 10676 6121 IRF6 LPS LPS-treated 2 0.3 Interestingly chronically LPS-treated SOD1 mice exhibited a more important loss of astrocytes than 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180927 14960605 241573 20996 11179 SOD1 SOD1 SOD1 3 3.0 Interestingly chronically LPS-treated SOD1 mice exhibited a more important loss of astrocytes than Veh-treated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180928 14960605 241573 20996 11179 SOD1 SOD1 SOD1 16 3.0 a more important loss of astrocytes than Veh-treated or nontreated SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180929 14960605 241575 20996 11179 SOD1 ALS ALS 13 1.7 compatible with a non-cell-autonomous mechanism of motor neuron death in ALS mice (Clement Clement et al. 2003 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180930 14960605 241576 10676 6121 IRF6 LPS LPS 2 0.3 The endotoxin LPS is able to activate microglia because these cells are of 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180931 14960605 241576 14211 7685 NDUFA2 CD14 CD14 17 1.0 microglia because these cells are of myeloid lineage and express CD14 and TLR4 receptors (Lacroix Lacroix et al. 1998 gamma (Moser 1 JUMiner_v2.2 1 0 0 2 7685 TotalCon:2<>1628|CD14|929|Complete__7685|NDUFA2|4695|Complete__<>AvaiableGeneRif=2<>BEST:7685|NDUFA2|0.000470291351227346<>ScoreDetail__7685|NDUFA2|0.000470291351227346__1628|CD14|0.000414718472071218__ 0 0 0 0 0 180932 14960605 241576 22219 11850 TLR4 TLR4 TLR4 19 1.6 these cells are of myeloid lineage and express CD14 and TLR4 receptors (Lacroix Lacroix et al. 1998 gamma (Moser Moser and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180933 14960605 241578 20996 11179 SOD1 ALS ALS 14 1.7 supported by studies on human patients with neurodegenerative disorders including ALS reporting the expression of molecules of adaptive immunity such as 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180934 14960605 241578 9353 4931 HLA-A MHC MHC 28 1.5 molecules of adaptive immunity such as major histocompatibility complex (MHC) MHC class I MHC class II and human histocompatibility leukocyte antigen 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180935 14960605 241578 9353 4931 HLA-A MHC MHC 31 1.5 immunity such as major histocompatibility complex (MHC) MHC class I MHC class II and human histocompatibility leukocyte antigen in brains spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180936 14960605 241578 11629 6493 LAMC2 CSF CSF 43 0.3 II and human histocompatibility leukocyte antigen in brains spinal cords CSF and sera (Kriz Kriz et al. 2002 Nguyen et al. 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 180937 14960605 241579 10676 6121 IRF6 LPS LPS 15 0.3 the gene encoding IL-12 was found in the CNS of LPS treated-SOD1 mice the cerebral tissue of these animals did not 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180938 14960605 241579 9905 5438 IFNG IFN-gamma IFN-gamma 30 1.1 tissue of these animals did not exhibit positive signal for IFN-gamma transcript 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180939 14960605 241580 3865 1678 CD4 CD4 CD4 6 0.3 Immunohistochemistry also failed to detect infiltrating CD4 and CD8 cells in the brain and spinal cord of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180940 14960605 241580 20996 11179 SOD1 SOD1 SOD1 17 3.0 and CD8 cells in the brain and spinal cord of SOD1 mice treated chronically with vehicle or LPS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180941 14960605 241580 10676 6121 IRF6 LPS LPS 24 0.3 spinal cord of SOD1 mice treated chronically with vehicle or LPS 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180942 14960605 241580 3870 1706 CD8A CD8 CD8 6 0.3 Immunohistochemistry also failed to detect infiltrating CD4 and CD8 cells in the brain and spinal cord of 4 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 180943 14960605 241580 3870 1706 CD8A CD8 CD8 8 0.1 Immunohistochemistry also failed to detect infiltrating CD4 and CD8 cells in the brain and spinal cord of SOD1 mice 6 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 180944 14960605 241581 20996 11179 SOD1 ALS ALS 24 1.7 with a specific transfer to an adaptive immune response in ALS mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180945 14960605 241582 10676 6121 IRF6 LPS LPS-treated 28 0.3 adaptive response may be toxic for the CNS of the LPS-treated SOD1 and SOD1 mice 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180946 14960605 241582 20996 11179 SOD1 SOD1 SOD1 29 3.0 response may be toxic for the CNS of the LPS-treated SOD1 and SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180947 14960605 241582 20996 11179 SOD1 SOD1 SOD1 29 3.0 response may be toxic for the CNS of the LPS-treated SOD1 and SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180948 14960605 241582 20996 11179 SOD1 SOD1 SOD1 31 3.0 be toxic for the CNS of the LPS-treated SOD1 and SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180949 14960605 241583 20996 11179 SOD1 SOD1 SOD1 10 3.0 For instance upregulation of the local adaptive immune response in SOD1 mice with Copaxone (glatiramer glatiramer acetate vaccination eliminates destructive self-compounds 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180950 14960605 241585 22551 11892 TNF TNF-alpha TNF-alpha 3 1.7 The proapoptotic cytokine TNF-alpha is likely to play a determinant role in this model 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180951 14960605 241586 10676 6121 IRF6 LPS LPS 2 0.3 The endotoxin LPS is able to trigger transcriptional activation of the gene encoding 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180952 14960605 241586 22551 11892 TNF TNF-alpha TNF-alpha 13 1.7 is able to trigger transcriptional activation of the gene encoding TNF-alpha in microglial cells across the CNS and TNF-alpha gene expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180953 14960605 241586 22551 11892 TNF TNF-alpha TNF-alpha 22 1.7 gene encoding TNF-alpha in microglial cells across the CNS and TNF-alpha gene expression progressively increased in the spinal cord of SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180954 14960605 241586 20996 11179 SOD1 SOD1 SOD1 33 3.0 TNF-alpha gene expression progressively increased in the spinal cord of SOD1 mice (Nadeau Nadeau and Rivest 2000 alpha levels are also 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180955 14960605 241586 11629 6493 LAMC2 CSF CSF 46 0.3 and Rivest 2000 alpha levels are also found in the CSF of ALS patients (Poloni Poloni et al. 2000 kappaB pathway 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 180956 14960605 241586 20996 11179 SOD1 ALS ALS 48 1.7 2000 alpha levels are also found in the CSF of ALS patients (Poloni Poloni et al. 2000 kappaB pathway which is 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180957 14960605 241586 7334 11936 FASLG FasL FasL 76 2.2 immune response (Nguyen Nguyen et al. 2002 alpha TNFRI TNFRII FasL and FasR will be essential to clarify the roles of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180958 14960605 241587 22217 11848 TLR2 TLR2 TLR2 7 5.1 In addition determining the endogenous ligand of TLR2 would help in deciphering the mechanistic details of its actions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180959 14960605 241592 20996 11179 SOD1 ALS ALS 7 1.7 Indeed the mechanisms that underlie 90% of ALS cases sporadic Parkinson's disease and Alzheimer's disease remain elusive (Nguyen 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180960 14960605 241593 20996 11179 SOD1 ALS ALS 2 1.7 Actually sporadic ALS may result from gene-environment interactions 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180961 14960605 241594 20996 11179 SOD1 ALS ALS 17 1.7 dietary glutamate-fat intake have been proposed as etiological causes for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180962 14960605 241597 20996 11179 SOD1 ALS ALS 20 1.7 infiltration of peripheral immune cells in the CNS of sporadic ALS cases have been reported (Nguyen Nguyen et al. 2002 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180963 14960605 241599 10676 6121 IRF6 LPS LPS 7 0.3 Beyond the toxicity of chronic administration of LPS in the mutant SOD1 mice our study constitutes a simple 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180964 14960605 241599 20996 11179 SOD1 SOD1 SOD1 11 3.0 the toxicity of chronic administration of LPS in the mutant SOD1 mice our study constitutes a simple example of genetic modulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180965 14960605 241600 20996 11179 SOD1 ALS ALS 17 1.7 bacterial infections in a wide diversity of neurodegenerative disorder including ALS we provide evidence here that environmental factors and innate immunity 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 180966 14960605 241604 10676 6121 IRF6 LPS LPS 6 0.3 Effect of a single bolus of LPS on TLR2 gene expression in the brains and spinal cords 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180967 14960605 241604 22217 11848 TLR2 TLR2 TLR2 8 5.1 Effect of a single bolus of LPS on TLR2 gene expression in the brains and spinal cords of SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180968 14960605 241604 20996 11179 SOD1 SOD1 SOD1 18 3.0 TLR2 gene expression in the brains and spinal cords of SOD1 mice and their WT littermates 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180969 14960605 241605 22217 11848 TLR2 TLR2 TLR2 11 5.1 (BF) BF and dark-field photomicrographs depict the expression pattern of TLR2 mRNA 24 hr after a single intraperitoneal injection of vehicle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180970 14960605 241605 10676 6121 IRF6 LPS LPS 24 0.3 after a single intraperitoneal injection of vehicle (Veh) Veh or LPS (1 1 mg/kg mg kg of body weight 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180971 14960605 241606 22217 11848 TLR2 TLR2 TLR2 9 5.1 Coronal and longitudinal sections were hybridized using a mouse TLR2 cRNA probe and dipped into NTB2 emulsion milk 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180972 14960605 241610 20996 11179 SOD1 SOD1 SOD1 17 3.0 within the brain and spinal cord of both WT and SOD1 mice that received an intraperitoneal bolus of LPS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180973 14960605 241610 10676 6121 IRF6 LPS LPS 25 0.3 WT and SOD1 mice that received an intraperitoneal bolus of LPS 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180974 14960605 241614 10676 6121 IRF6 LPS LPS-treated 22 0.3 main effect ( p _lt_ 0.0001 between the vehicle- and LPS-treated groups 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180975 14960605 241619 10676 6121 IRF6 LPS LPS 5 0.3 Chronic treatment with the endotoxin LPS increases the innate immune response and neurodegeneration in SOD1 mice 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180976 14960605 241619 20996 11179 SOD1 SOD1 SOD1 14 3.0 endotoxin LPS increases the innate immune response and neurodegeneration in SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180977 14960605 241620 22551 11892 TNF TNF-alpha TNF-alpha 14 1.7 dark-field photomicrographs depict representative examples of the hybridization signal for TNF-alpha ( B IL-12 ( C and TLR2 ( D mRNA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180978 14960605 241620 22217 11848 TLR2 TLR2 TLR2 24 5.1 hybridization signal for TNF-alpha ( B IL-12 ( C and TLR2 ( D mRNA in the reticular formation just above the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180979 14960605 241621 22217 11848 TLR2 TLR2 TLR2 13 5.1 interest to note that the hybridization signal for IL-12 and TLR2 overlaps with the fluorochrome FJB ( C D vs E 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180980 14960605 241623 22217 11848 TLR2 TLR2 TLR2 15 5.1 depict examples of microglial cells containing positive hybridization signal for TLR2 mRNA in the reticular formation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180981 14960605 241625 22217 11848 TLR2 TLR2 TLR2 0 5.1 TLR2 mRNA was thereafter hybridized on the same sections by means 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180982 14960605 241626 22217 11848 TLR2 TLR2 TLR2 7 5.1 Note the presence of the mRNA encoding TLR2 within parenchymal microglia (agglomeration agglomeration of silver grains within the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180983 14960605 241630 10676 6121 IRF6 LPS LPS-treated 7 0.3 Exacerbation of motor axon degeneration in chronically LPS-treated SOD1 mice accelerates disease progression 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180984 14960605 241630 20996 11179 SOD1 SOD1 SOD1 8 3.0 Exacerbation of motor axon degeneration in chronically LPS-treated SOD1 mice accelerates disease progression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180985 14960605 241631 20996 11179 SOD1 SOD1 SOD1 8 3.0 A Survival curves of transgenic mice expressing SOD1 challenged systemically with LPS or vehicle every 2 weeks 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180986 14960605 241631 10676 6121 IRF6 LPS LPS 12 0.3 Survival curves of transgenic mice expressing SOD1 challenged systemically with LPS or vehicle every 2 weeks 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180987 14960605 241632 10676 6121 IRF6 LPS LPS-treated 4 0.3 Disease progression of chronically LPS-treated mice is exacerbated by ~3 weeks 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180988 14960605 241633 10676 6121 IRF6 LPS LPS 15 0.3 of wild-type mice is unaffected by the same dose of LPS (see see Materials and Methods 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180989 14960605 241635 10676 6121 IRF6 LPS LPS 17 0.3 from normal mice treated chronically with vehicle (WT-Veh) WT-Veh or LPS (WT-LPS) WT-LPS and from SOD1 mice challenged chronically with vehicle 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180990 14960605 241635 20996 11179 SOD1 SOD1 SOD1 21 3.0 with vehicle (WT-Veh) WT-Veh or LPS (WT-LPS) WT-LPS and from SOD1 mice challenged chronically with vehicle (G37R-Veh) G37R-Veh or LPS (G37R-LPS) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180991 14960605 241635 10676 6121 IRF6 LPS LPS 29 0.3 from SOD1 mice challenged chronically with vehicle (G37R-Veh) G37R-Veh or LPS (G37R-LPS) G37R-LPS 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180992 14960605 241641 10676 6121 IRF6 LPS LPS-treated 9 0.3 Robust inflammatory response in ventral spinal horn of chronically LPS-treated SOD1 mice associated with massive degeneration of astrocytes 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 180993 14960605 241641 20996 11179 SOD1 SOD1 SOD1 10 3.0 Robust inflammatory response in ventral spinal horn of chronically LPS-treated SOD1 mice associated with massive degeneration of astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180994 14960605 241642 22551 11892 TNF TNF-alpha TNF-alpha 14 1.7 dark-field photomicrographs depict representative examples of the hybridization signal for TNF-alpha IL-12 and TLR2 mRNA in the L5 segment of the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180995 14960605 241642 22217 11848 TLR2 TLR2 TLR2 18 5.1 representative examples of the hybridization signal for TNF-alpha IL-12 and TLR2 mRNA in the L5 segment of the spinal cord ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180996 14960605 241643 22217 11848 TLR2 TLR2 TLR2 8 5.1 Here also the hybridization signal for IL-12 and TLR2 overlaps with the fluorochrome FJB 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180997 14960605 241646 20996 11179 SOD1 SOD1 SOD1 19 3.0 neurons and astrocytes in this region of spinal cord from SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180998 14960605 241651 22217 11848 TLR2 TLR2 TLR2 4 5.1 Relative expression levels of TLR2 hybridization signal in the brains of SOD1 mice and their 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 180999 14960605 241651 20996 11179 SOD1 SOD1 SOD1 11 3.0 expression levels of TLR2 hybridization signal in the brains of SOD1 mice and their wild-type littermates that received chronic systemic injections 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181000 14960605 241651 10676 6121 IRF6 LPS LPS 25 0.3 wild-type littermates that received chronic systemic injections of the endotoxin LPS or sterile saline solution (Veh) Veh 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181001 14960605 241658 10676 6121 IRF6 LPS LPS-treated 10 0.3 reported as mean values (_amp_#177;SEM) _amp_#177 SEM for vehicle- and LPS-treated animals of both mouse stains 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181002 14960605 241664 10676 6121 IRF6 LPS LPS 5 0.3 Acute and chronic administration of LPS in SOD1 failed to alter expression of endogenous and transgene 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181003 14960605 241664 20996 11179 SOD1 SOD1 SOD1 7 3.0 Acute and chronic administration of LPS in SOD1 failed to alter expression of endogenous and transgene SOD1 Six-month-old 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181004 14960605 241664 20996 11179 SOD1 SOD1 SOD1 16 3.0 in SOD1 failed to alter expression of endogenous and transgene SOD1 Six-month-old WT and transgenic SOD1 littermates were analyzed for SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181005 14960605 241664 20996 11179 SOD1 SOD1 SOD1 21 3.0 expression of endogenous and transgene SOD1 Six-month-old WT and transgenic SOD1 littermates were analyzed for SOD1 levels 24 hr after acute 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181006 14960605 241664 20996 11179 SOD1 SOD1 SOD1 26 3.0 SOD1 Six-month-old WT and transgenic SOD1 littermates were analyzed for SOD1 levels 24 hr after acute injection of LPS (1 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181007 14960605 241664 10676 6121 IRF6 LPS LPS 34 0.3 analyzed for SOD1 levels 24 hr after acute injection of LPS (1 1 mg/kg mg kg of body weight 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181008 14960605 241665 20996 11179 SOD1 SOD1 mSOD1 4 1.7 Expression of both endogenous mSOD1 and hSOD1 remained unaffected in spinal cord ( A lanes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181009 14960605 241665 20996 11179 SOD1 SOD1 hSOD1 6 1.7 Expression of both endogenous mSOD1 and hSOD1 remained unaffected in spinal cord ( A lanes 5-8 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181010 14960605 241665 20996 11179 SOD1 SOD1 SOD1 25 3.0 A lanes 5-8 and spleen ( B lanes 5-8 of SOD1 animals in response to saline (Veh) Veh or LPS injection 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181011 14960605 241665 10676 6121 IRF6 LPS LPS 33 0.3 of SOD1 animals in response to saline (Veh) Veh or LPS injection as detected by means of an antibody recognizing both 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181012 14960605 241665 20996 11179 SOD1 SOD1 SOD1 44 3.0 injection as detected by means of an antibody recognizing both SOD1 proteins 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181013 14960605 241666 20996 11179 SOD1 SOD1 mSOD1 7 1.7 The endotoxin also failed to significantly upregulate mSOD1 expression in WT animals ( A B lanes 1-4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181014 14960605 241667 20996 11179 SOD1 SOD1 SOD1s 4 1.7 Similar levels of both SOD1s were found in WT and SOD1 mice 48 hr after 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181015 14960605 241667 20996 11179 SOD1 SOD1 SOD1 10 3.0 Similar levels of both SOD1s were found in WT and SOD1 mice 48 hr after LPS or Veh administration (data data 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181016 14960605 241667 10676 6121 IRF6 LPS LPS 15 0.3 were found in WT and SOD1 mice 48 hr after LPS or Veh administration (data data not shown 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181017 14960605 241668 20996 11179 SOD1 SOD1 SOD1 1 3.0 In SOD1 mice that were chronically treated with LPS expression of mutant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181018 14960605 241668 10676 6121 IRF6 LPS LPS 8 0.3 In SOD1 mice that were chronically treated with LPS expression of mutant SOD1 (detected detected with an antibody directed 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181019 14960605 241668 20996 11179 SOD1 SOD1 SOD1 12 3.0 mice that were chronically treated with LPS expression of mutant SOD1 (detected detected with an antibody directed against the human transgene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181020 14960605 241669 20996 11179 SOD1 SOD1 SOD1 2 3.0 Lysates from SOD1 line 42 (L42) L42 overexpressing 2- to 2.5-fold the levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181021 14960605 241670 10676 6121 IRF6 LPS LPS 7 0.3 Thus neither acute nor chronic administration of LPS in SOD1 mice affected expression of endogenous and transgene SOD1 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181022 14960605 241670 20996 11179 SOD1 SOD1 SOD1 9 3.0 Thus neither acute nor chronic administration of LPS in SOD1 mice affected expression of endogenous and transgene SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181023 14960605 241670 20996 11179 SOD1 SOD1 SOD1 17 3.0 LPS in SOD1 mice affected expression of endogenous and transgene SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181024 14960605 241689 19573 10691 SDS SDS SDS 14 0.0 spinal cord were obtained by homogenization in SDS-urea beta-mercaptoethanol 0.5% SDS 8 M urea in phosphate buffer pH 7.4 with a 1 JUMiner_v2.2 1 0 0 2 19440 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:19440|SBDS|0.000304534248390088<>ScoreDetail__10691|SDS|0.000200734113328745__19440|SBDS|0.000304534248390088__ 0 0 0 0 0 181025 14960605 241692 20996 11179 SOD1 SOD1 SOD1 6 3.0 Membranes were incubated with antibodies against SOD1 (Biodesign; Biodesign Santa Cruz Biotechnology Santa Cruz CA alpha-tubulin (B512; 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181026 14960605 241697 22217 11848 TLR2 TLR2 TLR2 9 5.1 Semiquantitative analyses revealed similar increases in expression levels of TLR2 mRNA in different regions of the CNS in both WT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181027 14960605 241697 20996 11179 SOD1 SOD1 SOD1 21 3.0 in different regions of the CNS in both WT and SOD1 groups of mice challenged acutely with LPS ( Fig 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181028 14960605 241697 10676 6121 IRF6 LPS LPS 28 0.3 both WT and SOD1 groups of mice challenged acutely with LPS ( Fig 1 D E 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181029 14960605 241698 10676 6121 IRF6 LPS LPS-treated 9 0.3 The area postrema (AP) AP and spinal L5 segment of LPS-treated SOD1 mice did not exhibit a different hybridization signal when 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181030 14960605 241698 20996 11179 SOD1 SOD1 SOD1 10 3.0 area postrema (AP) AP and spinal L5 segment of LPS-treated SOD1 mice did not exhibit a different hybridization signal when compared 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181031 14960605 241699 20996 11179 SOD1 SOD1 SOD1 4 3.0 These results indicate that SOD1 are not more sensitive to the endotoxin and therefore exhibit 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181032 14960605 241700 10676 6121 IRF6 LPS LPS 4 0.3 Chronic systemic injections of LPS exacerbate disease progression and motor axon degeneration in SOD1 mice 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181033 14960605 241700 20996 11179 SOD1 SOD1 SOD1 13 3.0 of LPS exacerbate disease progression and motor axon degeneration in SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181034 14960605 241701 10676 6121 IRF6 LPS LPS 10 0.3 Remarkably a chronic systemic injection of an equal dose of LPS in presymptomatic 6-month-old SOD1 mice had a significant effect on 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181035 14960605 241701 20996 11179 SOD1 SOD1 SOD1 14 3.0 injection of an equal dose of LPS in presymptomatic 6-month-old SOD1 mice had a significant effect on their life span 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181036 14960605 241702 20996 11179 SOD1 SOD1 SOD1 8 3.0 Figure 2 A shows the survival curve of SOD1 mice (line line 29 treated chronically with Veh or LPS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181037 14960605 241702 10676 6121 IRF6 LPS LPS 17 0.3 SOD1 mice (line line 29 treated chronically with Veh or LPS 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181038 14960605 241703 20996 11179 SOD1 SOD1 SOD1 1 3.0 The SOD1 mice treated with vehicle ( n = 16 used as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181039 14960605 241703 20996 11179 SOD1 SOD1 SOD1 42 3.0 is not different from the life span of the nontreated SOD1 mice (Nguyen Nguyen et al. 2000 2001a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181040 14960605 241705 20996 11179 SOD1 SOD1 SOD1 0 3.0 SOD1 mice treated chronically with LPS ( n = 13 exhibited 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181041 14960605 241705 10676 6121 IRF6 LPS LPS 5 0.3 SOD1 mice treated chronically with LPS ( n = 13 exhibited an average life span of 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181042 14960605 241706 10676 6121 IRF6 LPS LPS 12 0.3 demonstrate that repeated intraperitoneal injections of a nontoxic dose of LPS in presymptomatic 6-month-old SOD1 mice exacerbated disease progression by 3 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181043 14960605 241706 20996 11179 SOD1 SOD1 SOD1 16 3.0 injections of a nontoxic dose of LPS in presymptomatic 6-month-old SOD1 mice exacerbated disease progression by 3 weeks 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181044 14960605 241707 20996 11179 SOD1 SOD1 SOD1 34 3.0 counted the number of axons in L5 ventral roots of SOD1 mice treated chronically with LPS or vehicle and killed at 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181045 14960605 241707 10676 6121 IRF6 LPS LPS 39 0.3 in L5 ventral roots of SOD1 mice treated chronically with LPS or vehicle and killed at 10 months of age 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181046 14960605 241708 10676 6121 IRF6 LPS LPS-treated 8 0.3 At this age the L5 ventral roots of LPS-treated SOD1 mice were smaller when compared with those dissected from 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181047 14960605 241708 20996 11179 SOD1 SOD1 SOD1 9 3.0 At this age the L5 ventral roots of LPS-treated SOD1 mice were smaller when compared with those dissected from Veh-SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181048 14960605 241709 10676 6121 IRF6 LPS LPS-treated 1 0.3 Furthermore LPS-treated SOD1 mice ( n = 5 had 358 _amp_#177 48 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181049 14960605 241709 20996 11179 SOD1 SOD1 SOD1 2 3.0 Furthermore LPS-treated SOD1 mice ( n = 5 had 358 _amp_#177 48 axons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181050 14960605 241709 20996 11179 SOD1 SOD1 SOD1 15 3.0 n = 5 had 358 _amp_#177 48 axons whereas Veh-treated SOD1 mice ( n = 4 had 478 _amp_#177 40 ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181051 14960605 241710 20996 11179 SOD1 SOD1 SOD1 14 3.0 there was a more severe loss of motor axons in SOD1 mice that received repeated injections with the endotoxin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181052 14960605 241712 10676 6121 IRF6 LPS LPS 8 0.3 It is noteworthy that the chronic injection of LPS in WT mice did not cause neurodegeneration (1033 1033 _amp_#177 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181053 14960605 241714 22217 11848 TLR2 TLR2 TLR2 12 5.1 assessed the transcriptional activation of the receptor of innate immunity TLR2 and the proapoptotic cytokine TNF-alpha in the SOD1 mice challenged 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181054 14960605 241714 22551 11892 TNF TNF-alpha TNF-alpha 17 1.7 the receptor of innate immunity TLR2 and the proapoptotic cytokine TNF-alpha in the SOD1 mice challenged chronically with LPS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181055 14960605 241714 20996 11179 SOD1 SOD1 SOD1 21 3.0 innate immunity TLR2 and the proapoptotic cytokine TNF-alpha in the SOD1 mice challenged chronically with LPS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181056 14960605 241714 10676 6121 IRF6 LPS LPS 26 0.3 proapoptotic cytokine TNF-alpha in the SOD1 mice challenged chronically with LPS 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181057 14960605 241715 22217 11848 TLR2 TLR2 TLR2 0 5.1 TLR2 is induced during disease progression of SOD1 mice and especially 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181058 14960605 241715 20996 11179 SOD1 SOD1 SOD1 7 3.0 TLR2 is induced during disease progression of SOD1 mice and especially in late stages where massive neurodegeneration occurs 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181059 14960605 241718 22217 11848 TLR2 TLR2 TLR2 5 5.1 Similarly a chronic expression of TLR2 might also trigger microglial apoptosis and thereby prevent the detrimental 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181060 14960605 241719 10676 6121 IRF6 LPS LPS-treated 10 0.3 The innate immune response was much more pronounced in chronically LPS-treated SOD1 mice than in Veh-treated SOD1 mice (Figs Figs 3 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181061 14960605 241719 20996 11179 SOD1 SOD1 SOD1 11 3.0 innate immune response was much more pronounced in chronically LPS-treated SOD1 mice than in Veh-treated SOD1 mice (Figs Figs 3 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181062 14960605 241719 20996 11179 SOD1 SOD1 SOD1 16 3.0 more pronounced in chronically LPS-treated SOD1 mice than in Veh-treated SOD1 mice (Figs Figs 3 4 5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181063 14960605 241720 22217 11848 TLR2 TLR2 TLR2 4 5.1 The robust expression of TLR2 mRNA ( Fig 3 D G is associated with strong 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181064 14960605 241720 22551 11892 TNF TNF-alpha TNF-alpha 24 1.7 strong hybridization signals for the genes encoding the proapoptotic cytokines TNF-alpha andinterleukin-12 (IL-12) IL-12 in degenerating efferent fiber tracts of the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181065 14960605 241724 10676 6121 IRF6 LPS LPS-treated 16 0.3 FJB-positive astrocytes were found in the spinal cord of chronically LPS-treated mutant SOD1 mice ( Fig 4 B 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181066 14960605 241724 20996 11179 SOD1 SOD1 SOD1 18 3.0 were found in the spinal cord of chronically LPS-treated mutant SOD1 mice ( Fig 4 B 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181067 14960605 241725 20996 11179 SOD1 ALS ALS 19 1.7 first pathological changes observed in patients and rodent models with ALS (Rothstein Rothstein et al. 1995 Bristol and Rothstein 1996 Bruijn 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 181068 14960605 241726 10676 6121 IRF6 LPS LPS-treated 8 0.3 Absence of adaptive immunity in the CNS of LPS-treated SOD1 mice 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181069 14960605 241726 20996 11179 SOD1 SOD1 SOD1 9 3.0 Absence of adaptive immunity in the CNS of LPS-treated SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181070 14960605 241727 9905 5438 IFNG IFN-gamma IFN-gamma 29 1.1 cord and brain tissues using highly sensitive probes for interferon-gamma IFN-gamma and IL-12 two cytokines essential for the transfer from the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181071 14960605 241728 10676 6121 IRF6 LPS LPS-treated 21 0.3 upregulation of IL-12 in degenerating CNS regions of the chronically LPS-treated SOD1 mice when compared with chronically Veh-treated SOD1 mice 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181072 14960605 241728 20996 11179 SOD1 SOD1 SOD1 22 3.0 of IL-12 in degenerating CNS regions of the chronically LPS-treated SOD1 mice when compared with chronically Veh-treated SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181073 14960605 241728 20996 11179 SOD1 SOD1 SOD1 29 3.0 the chronically LPS-treated SOD1 mice when compared with chronically Veh-treated SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181074 14960605 241729 9905 5438 IFNG IFN-gamma IFN-gamma 10 1.1 However in situ hybridization failed to detect positive signal for IFN-gamma transcript in the brain and spinal cord of SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181075 14960605 241729 20996 11179 SOD1 SOD1 SOD1 20 3.0 for IFN-gamma transcript in the brain and spinal cord of SOD1 mice treated acutely or chronically with the endotoxin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181076 14960605 241730 3865 1678 CD4 CD4 CD4 5 0.3 Immunohistochemistry using antibodies directed against CD4 or CD8 also failed to provide anatomical evidence of infiltrating 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181077 14960605 241730 10676 6121 IRF6 LPS LPS-treated 25 0.3 infiltrating T cells in the CNS of both vehicle- and LPS-treated SOD1 mice (data data not shown 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181078 14960605 241730 20996 11179 SOD1 SOD1 SOD1 26 3.0 T cells in the CNS of both vehicle- and LPS-treated SOD1 mice (data data not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181079 14960605 241730 3870 1706 CD8A CD8 CD8 7 0.1 Immunohistochemistry using antibodies directed against CD4 or CD8 also failed to provide anatomical evidence of infiltrating T cells 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181080 14960605 241732 10676 6121 IRF6 LPS LPS-treated 4 0.3 Accelerated neurodegeneration in chronically LPS-treated SOD1 mice is not attributable to an upregulation in levels 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181081 14960605 241732 20996 11179 SOD1 SOD1 SOD1 5 3.0 Accelerated neurodegeneration in chronically LPS-treated SOD1 mice is not attributable to an upregulation in levels of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181082 14960605 241733 10676 6121 IRF6 LPS LPS 4 0.3 Emerging evidence indicates that LPS can induce SOD1 which subsequently might play an important role 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181083 14960605 241733 20996 11179 SOD1 SOD1 SOD1 7 3.0 Emerging evidence indicates that LPS can induce SOD1 which subsequently might play an important role in mediating the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181084 14960605 241734 10676 6121 IRF6 LPS LPS-treated 11 0.3 to the understanding of mechanisms causing accelerated neurodegeneration in chronically LPS-treated SOD1 mice is whether LPS upregulates expression of the transgene 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181085 14960605 241734 20996 11179 SOD1 SOD1 SOD1 12 3.0 the understanding of mechanisms causing accelerated neurodegeneration in chronically LPS-treated SOD1 mice is whether LPS upregulates expression of the transgene SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181086 14960605 241734 10676 6121 IRF6 LPS LPS 16 0.3 causing accelerated neurodegeneration in chronically LPS-treated SOD1 mice is whether LPS upregulates expression of the transgene SOD1 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181087 14960605 241734 20996 11179 SOD1 SOD1 SOD1 22 3.0 SOD1 mice is whether LPS upregulates expression of the transgene SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181088 14960605 241735 20996 11179 SOD1 SOD1 SOD1 7 3.0 Indeed transgenic mice having higher levels of SOD1 (line line 42 exhibit a more aggressive pathology with previous 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181089 14960605 241736 20996 11179 SOD1 SOD1 SOD1 10 3.0 To address this question protein levels for both endogenous mouse SOD1 (mSOD1) mSOD1 and human mutant SOD1 (hSOD1) hSOD1 were determined 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181090 14960605 241736 20996 11179 SOD1 SOD1 mSOD1 11 1.7 this question protein levels for both endogenous mouse SOD1 (mSOD1) mSOD1 and human mutant SOD1 (hSOD1) hSOD1 were determined in SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181091 14960605 241736 20996 11179 SOD1 SOD1 SOD1 15 3.0 for both endogenous mouse SOD1 (mSOD1) mSOD1 and human mutant SOD1 (hSOD1) hSOD1 were determined in SOD1 mice in response to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181092 14960605 241736 20996 11179 SOD1 SOD1 hSOD1 16 1.7 endogenous mouse SOD1 (mSOD1) mSOD1 and human mutant SOD1 (hSOD1) hSOD1 were determined in SOD1 mice in response to acute or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181093 14960605 241736 20996 11179 SOD1 SOD1 SOD1 20 3.0 mSOD1 and human mutant SOD1 (hSOD1) hSOD1 were determined in SOD1 mice in response to acute or chronic injection of LPS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181094 14960605 241736 10676 6121 IRF6 LPS LPS 30 0.3 SOD1 mice in response to acute or chronic injection of LPS 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181095 14960605 241737 20996 11179 SOD1 SOD1 mSOD1 6 1.7 As shown in Figure 6 mSOD1 and hSOD1 levels in spinal cord and spleen were unchanged 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181096 14960605 241737 20996 11179 SOD1 SOD1 hSOD1 8 1.7 As shown in Figure 6 mSOD1 and hSOD1 levels in spinal cord and spleen were unchanged 24 hr 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181097 14960605 241737 10676 6121 IRF6 LPS LPS 23 0.3 and spleen were unchanged 24 hr after acute injection of LPS when compared with animals treated with vehicle solution (Veh) Veh 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181098 14960605 241739 20996 11179 SOD1 SOD1 SOD1 2 3.0 In addition SOD1 mice chronically challenged with LPS did not display increased levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181099 14960605 241739 10676 6121 IRF6 LPS LPS 7 0.3 In addition SOD1 mice chronically challenged with LPS did not display increased levels of both enzymes 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181100 14960605 241740 10676 6121 IRF6 LPS LPS 9 0.3 These results clearly indicate that toxicity caused by chronic LPS treatment is not caused by enhanced SOD1 expression 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 181101 14960605 241740 20996 11179 SOD1 SOD1 SOD1 16 3.0 caused by chronic LPS treatment is not caused by enhanced SOD1 expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181102 14960605 241742 20996 11179 SOD1 ALS ALS 18 1.7 Health Research (CIHR) CIHR and the Robert Packard Center for ALS Research at Johns Hopkins 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00127141958380738<>ScoreDetail__5468|IGFALS|0.000363923721587955__11179|SOD1|0.00127141958380738__ 0 0 0 0 0 181103 14960605 241748 20996 11179 SOD1 SOD1 SOD1 25 3.0 San Diego La Jolla CA for the kind gift of SOD1 mice (line line 29 Dr Y Imai (National National Institute 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181104 14960605 241748 479 352 AIF1 IBA1 iba1 43 1.3 Institute of Neuroscience Kodaira Tokyo Japan for the gift of iba1 antisera Dr A Israel (Institut Institut Pasteur Paris France for 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181105 14960605 241748 22551 11892 TNF TNF-alpha TNF-alpha 73 1.7 al Qu_amp_eacute bec Canada for the plasmid containing the mouse TNF-alpha cDNA Dr I Campbell (The The Scripps Research Institute La 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 181106 14960605 241748 9905 5438 IFNG IFN-gamma IFN-gamma 89 1.1 The Scripps Research Institute La Jolla CA for the mouse IFN-gamma cDNA Dr K Pahan (University University of Nebraska Lincoln NE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176355 15081582 235151 20996 11179 SOD1 ALS ALS 25 1.4 in these types of disease including amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176356 15081582 235153 17610 9605 PTGS2 COX COX 5 0.3 Inflammatory pathways involving the cyclooxygenase (COX) COX enzymes and subsequent generation of prostaglandins are potential target sites 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176357 15081582 235153 20996 11179 SOD1 ALS ALS 23 1.4 potential target sites for treatments to halt the progression of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176358 15081582 235154 17610 9605 PTGS2 COX COX 3 0.3 In the CNS COX enzymes are localized to neurons astrocytes and microglia and can 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176359 15081582 235155 17610 9605 PTGS2 COX COX 14 0.3 to be a dual role for the prostaglandin products of COX enzymes in the nervous system 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176360 15081582 235157 17610 9605 PTGS2 COX COX 6 0.3 In this review the pathways of COX activity and prostaglandin production form the center of the debate 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176361 15081582 235158 20996 11179 SOD1 ALS ALS 16 1.4 duality may affect future treatments for neurodegenerative diseases such as ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176362 15081582 235161 20996 11179 SOD1 ALS ALS 8 1.4 In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), ALS neuroinflammation is a key event although the cause and significance 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176363 15081582 235168 20996 11179 SOD1 ALS ALS 18 1.4 leukocytes marginating along postcapillary venules around areas of neuroinflammation in ALS ( Engelhardt et al. 1989 and Engelhardt et al. 1993 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176364 15081582 235175 17610 9605 PTGS2 COX COX 12 0.3 many aspects to neuroinflammation the pathways involving the cyclooxygenase (COX) COX enzyme and subsequent generation of prostaglandins clearly play a role 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176365 15081582 235176 20996 11179 SOD1 ALS ALS 13 1.4 represent potential sites for treatments to curb the progression of ALS ( McGeer and McGeer 2002 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176366 15081582 235177 17610 9605 PTGS2 COX COX 4 0.3 In this review the COX and prostaglandin pathways are used to frame the debate regarding 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176367 15081582 235178 17610 9605 PTGS2 COX COX 4 0.3 The significance of the COX pathway having both positive and negative outcomes in neurodegenerative disease 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176368 15081582 235178 20996 11179 SOD1 ALS ALS 31 1.4 its impact upon the design of future treatment strategies for ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176369 15081582 235179 17610 9605 PTGS2 COX COX 0 0.3 COX prostaglandins and neuroinflammation 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176370 15081582 235180 17610 9605 PTGS2 COX COX 1 0.3 Cyclooxygenase (COX) COX is the rate-limiting step in the production of prostaglandins 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176371 15081582 235182 17610 9605 PTGS2 COX COX 7 0.3 Arachidonic acid is the principal substrate for COX ( O'Banion 1999 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176372 15081582 235185 17610 9605 PTGS2 COX COX 4 0.3 There are two distinct COX isoenzymes known as COX-1 and COX-2 that are 65% homologous 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176373 15081582 235185 17609 9604 PTGS1 COX-1 COX-1 8 1.3 There are two distinct COX isoenzymes known as COX-1 and COX-2 that are 65% homologous 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176374 15081582 235185 17610 9605 PTGS2 COX-2 COX-2 8 3.8 There are two distinct COX isoenzymes known as COX-1 and COX-2 that are 65% homologous 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176375 15081582 235185 17610 9605 PTGS2 COX-2 COX-2 10 3.8 There are two distinct COX isoenzymes known as COX-1 and COX-2 that are 65% homologous 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176376 15081582 235186 17609 9604 PTGS1 COX-1 COX-1 0 1.3 COX-1 is constitutively expressed in most tissues and produces prostaglandins that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176377 15081582 235187 17610 9605 PTGS2 COX-2 COX-2 1 3.8 Conversely COX-2 was initially characterized as an inducible enzyme that is expressed 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176378 15081582 235188 17610 9605 PTGS2 COX-2 COX-2 0 3.8 COX-2 is now known to be constitutively expressed in the kidney 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176379 15081582 235189 17610 9605 PTGS2 COX-2 COX-2 4 3.8 Many cellular factors induce COX-2 expression including multiple growth factors cytokines interleukin (IL)-1_amp_#x3b2; IL -1_amp_#x3b2 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176380 15081582 235189 10676 6121 IRF6 LPS LPS 19 0.3 cytokines interleukin (IL)-1_amp_#x3b2; IL -1_amp_#x3b2 tumor necrosis factor-TNF lipopolysaccharide (LPS), LPS phorbol ester and elevated intracellular calcium concentration 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176381 15081582 235190 17610 9605 PTGS2 COX-2 COX-2 5 3.8 One transcription factor that influences COX-2 expression following exposure to these cellular factors is NF-_amp_#x3ba B 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176382 15081582 235191 17610 9605 PTGS2 COX-2 COX-2 0 3.8 COX-2 has an NF-_amp_#x3ba B binding site in its promoter region 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176383 15081582 235191 9808 5344 ICAM1 ICAM-1 ICAM-1 18 0.3 promoter region that is shared with other inflammatory mediators including ICAM-1 IL-2 IL-8 and complement ( Baldwin 1996 and Schmedtje et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176384 15081582 235191 10452 6001 IL2 IL-2 IL-2 19 1.3 region that is shared with other inflammatory mediators including ICAM-1 IL-2 IL-8 and complement ( Baldwin 1996 and Schmedtje et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176385 15081582 235191 10470 6025 IL8 IL-8 IL-8 20 1.3 that is shared with other inflammatory mediators including ICAM-1 IL-2 IL-8 and complement ( Baldwin 1996 and Schmedtje et al. 1997 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176386 15081582 235192 17610 9605 PTGS2 COX-2 COX-2 3 3.8 Specific inhibition of COX-2 upregulation can be achieved by factors that inhibit NF-_amp_#x3ba B 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176387 15081582 235192 10458 6014 IL4 IL-4 IL-4 16 1.3 achieved by factors that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 and glucocorticoids ( O'Banion 1999 (see see 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176388 15081582 235192 10480 5962 IL10 IL-10 IL-10 17 1.3 by factors that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 and glucocorticoids ( O'Banion 1999 (see see Table 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176389 15081582 235192 10490 5973 IL13 IL-13 IL-13 17 1.3 by factors that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 and glucocorticoids ( O'Banion 1999 (see see Table 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176390 15081582 235192 10490 5973 IL13 IL-13 IL-13 19 1.3 that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 and glucocorticoids ( O'Banion 1999 (see see Table 1 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176391 15081582 235193 17610 9605 PTGS2 COX COX 1 0.3 The COX enzymes (COX-1 COX-1 and COX-2 are more completely termed prostaglandin 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176392 15081582 235193 17609 9604 PTGS1 COX-1 COX-1 3 1.3 The COX enzymes (COX-1 COX-1 and COX-2 are more completely termed prostaglandin G/H G H 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176393 15081582 235193 17610 9605 PTGS2 COX-2 COX-2 3 3.8 The COX enzymes (COX-1 COX-1 and COX-2 are more completely termed prostaglandin G/H G H 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176394 15081582 235193 17610 9605 PTGS2 COX-2 COX-2 5 3.8 The COX enzymes (COX-1 COX-1 and COX-2 are more completely termed prostaglandin G/H G H synthases (1 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176395 15081582 235196 17610 9605 PTGS2 COX COX 6 0.3 Next the peroxidase action of the COX enzyme rapidly converts PGG 2 to prostaglandin H (PGH PGH 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176396 15081582 235198 16459 8893 PGF PGF PGF 19 0.3 prostaglandin D 2 (PGD PGD 2 prostaglandin F 2 (PGF PGF 2 prostaglandin (PGI PGI 2 also known as prostacyclin and 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 176397 15081582 235198 16457 8891 PGD PGD PGD 13 0.0 prostaglandin E 2 (PGE PGE 2 prostaglandin D 2 (PGD PGD 2 prostaglandin F 2 (PGF PGF 2 prostaglandin (PGI PGI 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176398 15081582 235198 1647 1044 BGN PGI PGI 23 0.0 PGD 2 prostaglandin F 2 (PGF PGF 2 prostaglandin (PGI PGI 2 also known as prostacyclin and thromboxane A 2 ( 1 JUMiner_v2.2 1 0 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.00055137110031907<>ScoreDetail__1044|BGN|0.00055137110031907__4458|GPI|0.000443515174554901__ 0 0 0 0 0 176399 15081582 235200 17610 9605 PTGS2 COX-2 COX-2 6 3.8 The second peroxidase step of the COX-2 reaction produces the free radical superoxide which may cause damage 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176400 15081582 235200 20996 11179 SOD1 ALS ALS 20 1.4 free radical superoxide which may cause damage to cells in ALS and other neurodegenerative diseases ( Kaufmann et al. 1996 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176401 15081582 235202 17610 9605 PTGS2 COX-2 COX-2 7 3.8 Although it is unlikely that upregulation of COX-2 activity alone produces enough free radicals to account for the 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176402 15081582 235203 17610 9605 PTGS2 COX COX 1 0.3 Both COX isoforms are detectable in various cell types in the CNS 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176403 15081582 235204 17610 9605 PTGS2 COX COX 5 0.3 Identification of the patterns of COX enzyme expression will permit us to form a hypothesis regarding 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176404 15081582 235204 17609 9604 PTGS1 COX-1 COX-1 19 1.3 permit us to form a hypothesis regarding the roles of COX-1 and -2 under normal conditions and during disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176405 15081582 235204 17610 9605 PTGS2 COX-2 COX-2 19 3.8 permit us to form a hypothesis regarding the roles of COX-1 and -2 under normal conditions and during disease 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176406 15081582 235205 17610 9605 PTGS2 COX COX 5 0.3 Analysis of the expression of COX isoforms in ALS models is expected to not only determine 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176407 15081582 235205 20996 11179 SOD1 ALS ALS 8 1.4 Analysis of the expression of COX isoforms in ALS models is expected to not only determine the role of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176408 15081582 235205 20996 11179 SOD1 ALS ALS 33 1.4 disease but also provide clues toward understanding the pathology of ALS itself 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176409 15081582 235206 17610 9605 PTGS2 COX COX 23 0.3 we will better understand the pathogenic and protective implications of COX activity in ALS 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176410 15081582 235206 20996 11179 SOD1 ALS ALS 26 1.4 understand the pathogenic and protective implications of COX activity in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176411 15081582 235207 17610 9605 PTGS2 COX COX 0 0.3 COX and neurons 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176412 15081582 235208 17609 9604 PTGS1 COX-1 COX-1 0 1.3 COX-1 is constitutively expressed throughout the normal brain ( Kawasaki et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176413 15081582 235209 17610 9605 PTGS2 COX-2 COX-2 2 3.8 Immunoreactivity for COX-2 is present in the dendritic spines of cortical neurons and 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176414 15081582 235211 17610 9605 PTGS2 COX-2 COX-2 12 3.8 display a distinct alteration in the laminar pattern of cortical COX-2 immunoreactivity ( Kaufmann et al. 1996 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176415 15081582 235212 17610 9605 PTGS2 COX-2 COX-2 0 3.8 COX-2 immunoreactivity also is observed in the soma and throughout the 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176416 15081582 235213 17610 9605 PTGS2 COX-2 COX-2 1 3.8 Constitutive COX-2 is in the spinal dorsal and ventral horns as well 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176417 15081582 235214 17610 9605 PTGS2 COX COX 5 0.3 Indeed the antihyperalgesic activity of COX inhibitors is associated with regulation of constitutive COX-2 in the 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176418 15081582 235214 17610 9605 PTGS2 COX-2 COX-2 13 3.8 activity of COX inhibitors is associated with regulation of constitutive COX-2 in the spinal cord ( Svensson and Yaksh 2002 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176419 15081582 235215 17610 9605 PTGS2 COX-2 COX-2 4 3.8 Although a role for COX-2 in healthy cells is not clear under pathological conditions the 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176420 15081582 235215 17610 9605 PTGS2 COX-2 COX-2 17 3.8 cells is not clear under pathological conditions the induction of COX-2 in neurons has been well demonstrated 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176421 15081582 235216 17610 9605 PTGS2 COX-2 COX-2 0 3.8 COX-2 was originally localized in neurons using in situ hybridization 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176422 15081582 235217 17610 9605 PTGS2 COX-2 COX-2 6 3.8 Following a single maximal electroconvulsive seizure COX-2 is rapidly induced in hippocampal and cortical neurons peaking between 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176423 15081582 235218 17610 9605 PTGS2 COX-2 COX-2 16 3.8 the N -methyl--aspartic acid (NMDA) NMDA receptor completely inhibits the COX-2 induction implying that NMDA receptor activation is involved in the 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176424 15081582 235218 17610 9605 PTGS2 COX-2 COX-2 29 3.8 that NMDA receptor activation is involved in the upregulation of COX-2 in these neurons 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176425 15081582 235219 17610 9605 PTGS2 COX-2 COX-2 9 3.8 In addition administration of the glucocorticoid dexamethasone markedly decreases COX-2 induction but only in the neocortex ( Yamagata et al. 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176426 15081582 235220 17610 9605 PTGS2 COX-2 COX-2 4 3.8 This study suggests that COX-2 upregulation in neurons is dependent upon glutamatergic activity at the 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176427 15081582 235222 17610 9605 PTGS2 COX-2 COX-2 23 3.8 basalis can induce seizures in a rat and subsequently upregulate COX-2 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176428 15081582 235225 17610 9605 PTGS2 COX-2 COX-2 3 3.8 (1997) 1997 showed that COX-2 induction overlaps with the development of neuronal apoptosis 8 h 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176429 15081582 235226 17610 9605 PTGS2 COX-2 COX-2 26 3.8 that precede neuronal death and correlates with the induction of COX-2 mRNA 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176430 15081582 235227 17610 9605 PTGS2 COX-2 COX-2 13 3.8 prostaglandin production and subsequent cell death is attenuated by a COX-2 inhibitor but not with a COX-1 selective inhibitor ( Hewett 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176431 15081582 235227 17609 9604 PTGS1 COX-1 COX-1 19 1.3 is attenuated by a COX-2 inhibitor but not with a COX-1 selective inhibitor ( Hewett et al. 2000 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176432 15081582 235228 17610 9605 PTGS2 COX-2 COX-2 9 3.8 In addition genetic studies show that transgenic mice overexpressing COX-2 specifically in neurons are more susceptible to excitotoxicity ( Kelley 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176433 15081582 235229 17610 9605 PTGS2 COX-2 COX-2 2 3.8 In contrast COX-2 knockout mice experience reduced neuronal death compared to wild-type mice 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176434 15081582 235230 17610 9605 PTGS2 COX-2 COX-2 0 3.8 COX-2 is induced in models of cerebral ischemia 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176435 15081582 235232 17610 9605 PTGS2 COX-2 COX-2 12 3.8 but especially the penumbra region show a significant increase in COX-2 mRNA in the ischemic area ipsilateral to the occlusion 4 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176436 15081582 235233 17610 9605 PTGS2 COX-2 COX-2 9 3.8 There is a direct correlation between the extent of COX-2 mRNA induction at 4 h and the severity of subsequent 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176437 15081582 235234 17610 9605 PTGS2 COX-2 COX-2 11 3.8 the glutamate antagonist agent MK-801 significantly prevents the induction of COX-2 in the penumbra region ( Collaco-Moraes et al. 1996 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176438 15081582 235235 17610 9605 PTGS2 COX-2 COX-2 11 3.8 studies provide evidence of a linkage between glutamate activity subsequent COX-2 induction and finally apoptotic death in neurons 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176439 15081582 235236 17610 9605 PTGS2 COX-2 COX-2 10 3.8 Although increased extracellular glutamate regardless of its source can induce COX-2 in neurons the full consequences of this induction in neurons 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176440 15081582 235237 17610 9605 PTGS2 COX-2 COX-2 0 3.8 COX-2 activity correlates with apoptosis in certain models however from studies 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176441 15081582 235237 17610 9605 PTGS2 COX-2 COX-2 21 3.8 conducted thus far it is not clear which products of COX-2 induction are contributing to neuronal death which are helping neurons 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176442 15081582 235238 17610 9605 PTGS2 COX COX 0 0.3 COX and astrocytes 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176443 15081582 235239 17610 9605 PTGS2 COX-2 COX-2 4 3.8 In the nervous system COX-2 induction following cell activation or injury is not restricted to 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176444 15081582 235239 17610 9605 PTGS2 COX-2 COX-2 20 3.8 injury is not restricted to neurons since astrocytes also upregulate COX-2 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176445 15081582 235241 17610 9605 PTGS2 COX-2 COX-2 6 3.8 IL-1_amp_#x3b2 causes a rapid induction of COX-2 peaking at 2 h and returning to baseline by 24 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176446 15081582 235242 17609 9604 PTGS1 COX-1 COX-1 6 1.3 There is no correlate change in COX-1 mRNA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176447 15081582 235243 17610 9605 PTGS2 COX-2 COX-2 8 3.8 Dexamethasone can attenuate IL-1_amp_#x3b2 -mediated PGE 2 secretion and COX-2 expression ( O'Banion et al. 1996 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176448 15081582 235244 17610 9605 PTGS2 COX-2 COX-2 1 3.8 Astrocytic COX-2 is also induced by LPS TNF basic fibroblast growth factor 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176449 15081582 235244 10676 6121 IRF6 LPS LPS 6 0.3 Astrocytic COX-2 is also induced by LPS TNF basic fibroblast growth factor (bFGF), bFGF and phorbol ester 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176450 15081582 235244 22551 11892 TNF TNF TNF 7 1.2 Astrocytic COX-2 is also induced by LPS TNF basic fibroblast growth factor (bFGF), bFGF and phorbol ester ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176451 15081582 235244 14766 8053 NUDT6 bFGF bFGF 13 1.0 also induced by LPS TNF basic fibroblast growth factor (bFGF), bFGF and phorbol ester ( O'Banion 1999 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176452 15081582 235246 17610 9605 PTGS2 COX-2 COX-2 9 3.8 Although there is strong evidence for the induction of COX-2 in astrocytes in vitro there are few studies that confirm 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176453 15081582 235247 17610 9605 PTGS2 COX-2 COX-2 0 3.8 COX-2 immunoreactive astrocytes have been observed in the hippocampus at 1_amp_#x2013 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176454 15081582 235248 17610 9605 PTGS2 COX-2 COX-2 11 3.8 the cortex in Alzheimer's disease in situ hybridization with a COX-2 riboprobe revealed signal in a small proportion of GFAP-positive astrocytes 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176455 15081582 235248 8254 4235 GFAP GFAP GFAP-positive 20 0.0 a COX-2 riboprobe revealed signal in a small proportion of GFAP-positive astrocytes ( Chang et al. 1996 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176456 15081582 235249 17610 9605 PTGS2 COX-2 COX-2 2 3.8 In addition COX-2 colocalizes with GFAP in infarcted human brains ( Sairanen et 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176457 15081582 235249 8254 4235 GFAP GFAP GFAP 5 0.0 In addition COX-2 colocalizes with GFAP in infarcted human brains ( Sairanen et al. 1998 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176458 15081582 235251 17610 9605 PTGS2 COX-2 COX-2 8 3.8 Most in vitro studies are short-term and demonstrate COX-2 induction in the order of hours after the insult 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176459 15081582 235252 17610 9605 PTGS2 COX-2 COX-2 13 3.8 vitro models may skew attempts to ascertain the significance of COX-2 activity in neurodegenerative disease 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176460 15081582 235253 17610 9605 PTGS2 COX-2 COX-2 10 3.8 In the context of neurodegenerative diseases the chronic induction of COX-2 will be more pathophysiologically relevant 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176461 15081582 235254 17610 9605 PTGS2 COX COX 0 0.3 COX and microglia 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176462 15081582 235255 17609 9604 PTGS1 COX-1 COX-1 15 1.3 types in the CNS microglia appear to predominantly express the COX-1 isoform ( Yermakova et al. 1999 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176463 15081582 235256 17609 9604 PTGS1 COX-1 COX-1 2 1.3 In addition COX-1 positive microglia accumulate at sites of neuronal degeneration including traumatic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176464 15081582 235257 17610 9605 PTGS2 COX COX 7 0.3 The significance of the different isoform of COX expression in this cell type is not clear 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176465 15081582 235258 9353 4931 HLA-A MHC MHC 13 0.6 brain injury by making morphologic changes producing proinflammatory cytokines expressing MHC class II antigens and increasing phagocytosis ( Kreutzberg 1996 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176466 15081582 235259 10676 6121 IRF6 LPS LPS 18 0.3 to release PGE 2 and PGD 2 in response to LPS stimulation ( Gebicke-Haerter et al. 1989 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176467 15081582 235259 16457 8891 PGD PGD PGD 13 0.0 in culture acquire the capacity to release PGE 2 and PGD 2 in response to LPS stimulation ( Gebicke-Haerter et al. 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176468 15081582 235260 10676 6121 IRF6 LPS LPS 6 0.3 In cultures of neonatal rat microglia LPS induces equivalent levels of PGD 2 and TXA 2 over 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176469 15081582 235260 16457 8891 PGD PGD PGD 11 0.0 cultures of neonatal rat microglia LPS induces equivalent levels of PGD 2 and TXA 2 over the initial 8 h 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176470 15081582 235264 17610 9605 PTGS2 COX-2 COX-2 14 3.8 mechanisms than macrophages fibroblasts and synovial cells that can induce COX-2 via the cytokines TNF IL-1_amp_#x3b2 and IL-6 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176471 15081582 235264 22551 11892 TNF TNF TNF 18 1.2 and synovial cells that can induce COX-2 via the cytokines TNF IL-1_amp_#x3b2 and IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176472 15081582 235264 10463 6018 IL6 IL-6 IL-6 22 1.3 that can induce COX-2 via the cytokines TNF IL-1_amp_#x3b2 and IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176473 15081582 235265 17610 9605 PTGS2 COX-2 COX-2 5 3.8 None of these agents induce COX-2 or NF-_amp_#x3ba B expression in na_amp_#xef ve microglial cells 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176474 15081582 235266 10676 6121 IRF6 LPS LPS 5 0.3 In cultured rat brain microglia LPS induces COX-2 expression that is prevented in the presence of 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176475 15081582 235266 17610 9605 PTGS2 COX-2 COX-2 7 3.8 In cultured rat brain microglia LPS induces COX-2 expression that is prevented in the presence of inhibitors of 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176476 15081582 235266 14352 7794 NFKB1 NF-kappaB NF-kappaB 18 0.3 expression that is prevented in the presence of inhibitors of NF-kappaB (dexamethasone, dexamethasone the antioxidant pyrrolidine dithiocarbamate and the protein C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176477 15081582 235267 10676 6121 IRF6 LPS LPS-stimulated 5 0.3 Thus NF-_amp_#x3ba B is involved in LPS-stimulated microglial COX-2 expression ( Bauer et al. 1997 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176478 15081582 235267 17610 9605 PTGS2 COX-2 COX-2 7 3.8 Thus NF-_amp_#x3ba B is involved in LPS-stimulated microglial COX-2 expression ( Bauer et al. 1997 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176479 15081582 235268 17609 9604 PTGS1 COX-1 COX-1 2 1.3 Although increased COX-1 in microglia is observed injury paradigms there are little data 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176480 15081582 235268 17610 9605 PTGS2 COX-2 COX-2 17 3.8 injury paradigms there are little data indicating the expression of COX-2 in microglia in vivo 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176481 15081582 235270 17610 9605 PTGS2 COX-2 COX-2 2 3.8 (1998) 1998 showed COX-2 immunostaining of cells with a microglial-like morphology in infarcted human 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176482 15081582 235272 17610 9605 PTGS2 COX COX 8 0.3 After examining the locations and activity of the COX enzymes throughout the CNS a discussion of the potential actions 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176483 15081582 235276 1647 1044 BGN PGI PGI 16 0.0 by thromboxane A 2 (TXA TXA 2 but inhibited by PGI 2 ( Wu and Thiagarajan 1996 1 JUMiner_v2.2 1 0 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.00055137110031907<>ScoreDetail__1044|BGN|0.00055137110031907__4458|GPI|0.000443515174554901__ 0 0 0 0 0 176484 15081582 235278 16457 8891 PGD PGD PGD 0 0.0 PGD 2 produces sleep but wakefulness is promoted by PGE 2 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176485 15081582 235279 17610 9605 PTGS2 COX-2 COX-2 7 3.8 In a carrageenin-induced pleurisy model in rats COX-2 induction peaks at 2 h with maximal PGE 2 production 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176486 15081582 235280 17610 9605 PTGS2 COX-2 COX-2 4 3.8 At a later time COX-2 increases again but this time with increased levels of PGD 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176487 15081582 235280 16457 8891 PGD PGD PGD 14 0.0 COX-2 increases again but this time with increased levels of PGD 2 and PGJ 2 and decreased inflammation 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176488 15081582 235281 17610 9605 PTGS2 COX-2 COX-2 12 3.8 different inflammatory responses are modulated by the addition of a COX-2 inhibitor that causes inhibition of the early inflammatory response but 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176489 15081582 235282 17610 9605 PTGS2 COX-2 COX-2 13 3.8 to be a dual role for the products of the COX-2 enzyme in the nervous system 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176490 15081582 235288 16440 8884 PGA PGA PGA 2 0.6 For example PGA 1 that is derived from PGE 2 blunts NMDA receptor 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 176491 15081582 235288 7708 3811 FOXG1 QIN Qin 32 0.0 heat shock proteins and inhibition of NF-_amp_#x3ba B activity ( Qin et al. 2001 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176492 15081582 235289 12354 6886 MAPK9 SAPK SAPK 39 1.3 apoptotic signals through blocking the activation of stress-activated protein kinase SAPK c-Jun N-terminal kinase (JNK) JNK ( Kawamura et al. 1999 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176493 15081582 235289 10824 6204 JUN c-Jun c-Jun 39 0.3 signals through blocking the activation of stress-activated protein kinase SAPK c-Jun N-terminal kinase (JNK) JNK ( Kawamura et al. 1999 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176494 15081582 235289 12349 6881 MAPK8 JNK JNK 43 0.3 activation of stress-activated protein kinase SAPK c-Jun N-terminal kinase (JNK) JNK ( Kawamura et al. 1999 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176495 15081582 235291 1647 1044 BGN PGI PGI 2 0.0 Analogs of PGI 2 also are neuroprotective ( Watanabe et al. 1999 1 JUMiner_v2.2 1 0 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.00055137110031907<>ScoreDetail__1044|BGN|0.00055137110031907__4458|GPI|0.000443515174554901__ 0 0 0 0 0 176496 15081582 235294 20996 11179 SOD1 ALS ALS 9 1.4 In both in vitro and in vivo models of ALS strong evidence is obtained for prostaglandins mediating apoptosis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176497 15081582 235295 17610 9605 PTGS2 COX-2 COX-2 5 3.8 In these models inhibition of COX-2 can delay disease onset and progression 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176498 15081582 235296 17610 9605 PTGS2 COX-2 COX-2 4 3.8 Thus prostaglandin products of COX-2 appear to play a critical role in the development of 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176499 15081582 235297 17597 9594 PTGER2 EP2 EP2 18 0.6 2 induce apoptosis in a dose-dependent manner likely via the EP2 receptor and subsequent activation of caspase-3 ( Takadera et al. 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00127562619623389<>ScoreDetail__9594|PTGER2|0.00127562619623389__14534|SPAG11B|0.00040037692049485__ 0 0 0 0 0 176500 15081582 235299 17610 9605 PTGS2 COX-2 COX-2 2 3.8 Addition of COX-2 inhibitors prevents both PGE 2 production and kainic acid-induced neuronal 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176501 15081582 235301 17610 9605 PTGS2 COX-2 COX-2 23 3.8 -induced glutamate may lead to further excitatory cell activation and COX-2 induction 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176502 15081582 235302 17610 9605 PTGS2 COX-2 COX-2 8 3.8 This mechanism is highlighted in a model of COX-2 overexpression that displays acceleration of glutamate-mediated neuronal apoptosis ( Mirjany 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176503 15081582 235303 16457 8891 PGD PGD PGD 15 0.0 PGJ 2 a natural peroxisome proliferator-activated receptor-gamma ligand formed from PGD 2 induces apoptosis in both human astrocytes ( Chattopadhyay et 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176504 15081582 235304 16457 8891 PGD PGD PGD 2 0.0 Exposure to PGD 2 synthase induces apoptosis in PC12 neuronal cells via caspase-3 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176505 15081582 235305 16457 8891 PGD PGD PGD 16 0.0 with anti-PGD 2 synthase antibody or selenium that both inhibit PGD 2 synthase activity 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176506 15081582 235307 16459 8893 PGF PGF PGF 9 0.3 In addition PGE 1 PGE 2 and PGF 2 all inhibit PGD 2 synthase-induced apoptosis while PGH 2 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 176507 15081582 235307 16457 8891 PGD PGD PGD 13 0.0 addition PGE 1 PGE 2 and PGF 2 all inhibit PGD 2 synthase-induced apoptosis while PGH 2 has no effect ( 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 176508 15081582 235315 17610 9605 PTGS2 COX COX 13 0.3 of prostaglandins also are different depending upon the presence of COX inhibitors 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176509 15081582 235316 16459 8893 PGF PGF PGF 4 0.3 Both PGE 2 and PGF 2 at micromolar concentrations prevent NMDA-induced death in cultured cortical 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 176510 15081582 235317 17610 9605 PTGS2 COX-2 COX-2 9 3.8 Independently these cells are protected from death by the COX-2 inhibitor APHS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176511 15081582 235318 16459 8893 PGF PGF PGF 19 0.3 PGE 2 abrogates APHS neuroprotection but coapplication of APHS with PGF 2 maintains the APHS neuroprotective effect ( Carlson 2003 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 176512 15081582 235319 17610 9605 PTGS2 COX-2 COX-2 18 3.8 on cell survival in the presence or absence of a COX-2 inhibitor may be because COX-2 activity results in the generation 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176513 15081582 235319 17610 9605 PTGS2 COX-2 COX-2 23 3.8 presence or absence of a COX-2 inhibitor may be because COX-2 activity results in the generation of multiple prostaglandins with potentially 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176514 15081582 235320 17610 9605 PTGS2 COX-2 COX-2 1 3.8 When COX-2 is inhibited both the pro- and anti-apoptotic products are lost 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176515 15081582 235321 17610 9605 PTGS2 COX-2 COX-2 2 3.8 However when COX-2 is not inhibited multiple prostaglandins are present that can act 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176516 15081582 235324 16440 8884 PGA PGA PGA 1 0.6 Prostaglandins PGA 1 PGA 2 and PGJ 2 all can suppress NF-_amp_#x3ba 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 176517 15081582 235324 16440 8884 PGA PGA PGA 4 0.6 Prostaglandins PGA 1 PGA 2 and PGJ 2 all can suppress NF-_amp_#x3ba B activation 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 176518 15081582 235324 17610 9605 PTGS2 COX-2 COX-2 18 3.8 2 all can suppress NF-_amp_#x3ba B activation and thus suppress COX-2 induction as well as other inflammatory mediators including inducible nitric 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176519 15081582 235335 17609 9604 PTGS1 COX-1 COX-1 15 1.3 in which the significance of the differential expression of the COX-1 and COX-2 isoforms may arise 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176520 15081582 235335 17610 9605 PTGS2 COX-2 COX-2 15 3.8 in which the significance of the differential expression of the COX-1 and COX-2 isoforms may arise 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176521 15081582 235335 17610 9605 PTGS2 COX-2 COX-2 17 3.8 the significance of the differential expression of the COX-1 and COX-2 isoforms may arise 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176522 15081582 235336 17609 9604 PTGS1 COX-1 COX-1 1 1.3 Since COX-1 increases in activated microglia and is not regulated by NF-_amp_#x3ba 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176523 15081582 235336 17610 9605 PTGS2 COX-2 COX-2 24 3.8 microglial origin can regulate the activity of NF-_amp_#x3ba B and COX-2 in adjacent neurons without the same feedback regulation affecting the 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176524 15081582 235337 20996 11179 SOD1 ALS ALS 0 1.4 ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176525 15081582 235338 20996 11179 SOD1 ALS ALS 0 1.4 ALS is the most common motor neuron disease in adults 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176526 15081582 235344 20996 11179 SOD1 ALS ALS 5 1.4 The pathogenic mechanisms underlying idiopathic ALS remain unknown 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176527 15081582 235345 20996 11179 SOD1 ALS ALS 1 1.4 Although ALS is described as a motor neuron disease it is likely 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176528 15081582 235347 20996 11179 SOD1 ALS ALS 10 1.4 The familial disorder is clinically and pathologically indistinguishable from sporadic ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176529 15081582 235348 20996 11179 SOD1 SOD1 SOD1 10 1.4 mutations in the cytosolic protein copper_amp_#x2013 zinc superoxide dismutase (SOD1) SOD1 were reported in several FALS families 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176530 15081582 235349 20996 11179 SOD1 SOD1 SOD1 6 1.4 Since then over 95 mutations in SOD1 have been identified in patients with FALS ( Mithal et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176531 15081582 235350 20996 11179 SOD1 SOD1 SOD1 0 1.4 SOD1 is a metalloenzyme that detoxifies the superoxide anion to form 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176532 15081582 235351 20996 11179 SOD1 SOD1 SOD1 1 1.4 However SOD1 mutations account for only 20% of familial ALS ( Feldman 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176533 15081582 235351 20996 11179 SOD1 ALS ALS 9 1.4 However SOD1 mutations account for only 20% of familial ALS ( Feldman 1999 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176534 15081582 235352 20996 11179 SOD1 SOD1 SOD1 2 1.4 Because mutant SOD1 explains only a very small subset of ALS pathology it 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176535 15081582 235352 20996 11179 SOD1 ALS ALS 10 1.4 Because mutant SOD1 explains only a very small subset of ALS pathology it is very likely that ALS is a disorder 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176536 15081582 235352 20996 11179 SOD1 ALS ALS 17 1.4 small subset of ALS pathology it is very likely that ALS is a disorder with heterogeneous causes 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176537 15081582 235354 20996 11179 SOD1 ALS ALS 9 1.4 Common theories to explain the pathogenic mechanism of idiopathic ALS include (1) 1 excitotoxic damage secondary to excessive glutamate (2) 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176538 15081582 235356 20996 11179 SOD1 ALS ALS 7 1.4 Although the root cause or causes of ALS remain unclear there is new interest in the role of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176539 15081582 235357 20996 11179 SOD1 ALS ALS 0 1.4 ALS spinal cord tissue is characterized by neuroinflammatory changes consistent with 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176540 15081582 235359 20996 11179 SOD1 ALS ALS 18 1.4 major relevance to developing new clinical therapies for treatment of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176541 15081582 235360 17610 9605 PTGS2 COX COX 0 0.3 COX prostaglandins and ALS 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176542 15081582 235360 20996 11179 SOD1 ALS ALS 3 1.4 COX prostaglandins and ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176543 15081582 235361 17610 9605 PTGS2 COX-2 COX-2 0 3.8 COX-2 activity appears to play an important role in ALS 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176544 15081582 235361 20996 11179 SOD1 ALS ALS 9 1.4 COX-2 activity appears to play an important role in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176545 15081582 235362 17610 9605 PTGS2 COX-2 COX-2 4 3.8 In many different models COX-2 upregulation occurs concurrently with ALS disease events 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176546 15081582 235362 20996 11179 SOD1 ALS ALS 9 1.4 In many different models COX-2 upregulation occurs concurrently with ALS disease events 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176547 15081582 235363 17610 9605 PTGS2 COX-2 COX-2 0 3.8 COX-2 and PGE 2 are significantly elevated upwards of sevenfold in 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176548 15081582 235363 20996 11179 SOD1 ALS ALS 18 1.4 of sevenfold in postmortem spinal cords of patients with sporadic ALS ( Almer et al. 2001 and Yasojima et al. 2001 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176549 15081582 235364 20996 11179 SOD1 SOD1 SOD1-expressing 8 1.4 In the spinal cords of transgenic mutant human SOD1-expressing (mSOD1) mSOD1 mice there is increased expression of COX-2 but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176550 15081582 235364 20996 11179 SOD1 SOD1 mSOD1 9 1.4 In the spinal cords of transgenic mutant human SOD1-expressing (mSOD1) mSOD1 mice there is increased expression of COX-2 but not COX-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176551 15081582 235364 17610 9605 PTGS2 COX-2 COX-2 16 3.8 human SOD1-expressing (mSOD1) mSOD1 mice there is increased expression of COX-2 but not COX-1 mRNA 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176552 15081582 235364 17609 9604 PTGS1 COX-1 COX-1 19 1.3 mSOD1 mice there is increased expression of COX-2 but not COX-1 mRNA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176553 15081582 235365 17610 9605 PTGS2 COX-2 COX-2 0 3.8 COX-2 mRNA and protein levels COX catalytic activity and PGE 2 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176554 15081582 235365 17610 9605 PTGS2 COX COX 5 0.3 COX-2 mRNA and protein levels COX catalytic activity and PGE 2 levels are all increased in 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176555 15081582 235365 20996 11179 SOD1 SOD1 mSOD1 24 1.4 increased in the spinal cord but not the cerebellum of mSOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176556 15081582 235366 20996 11179 SOD1 ALS ALS 14 1.4 glutamate-induced motor neuron loss this prominent prostaglandin is implicated in ALS pathogenesis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176557 15081582 235367 17610 9605 PTGS2 COX-2 COX-2 0 3.8 COX-2 levels in mSOD1 mice are increased in both early symptomatic 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176558 15081582 235367 20996 11179 SOD1 SOD1 mSOD1 3 1.4 COX-2 levels in mSOD1 mice are increased in both early symptomatic and end-stage disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176559 15081582 235369 17610 9605 PTGS2 COX-2 COX-2 3 3.8 Selective inhibition of COX-2 with SC236 protects motor neurons in an organotypic cell culture 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176560 15081582 235369 20996 11179 SOD1 ALS ALS 16 1.4 protects motor neurons in an organotypic cell culture model of ALS ( Drachman and Rothstein 2000 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176561 15081582 235370 17610 9605 PTGS2 COX COX 6 0.3 In addition several drugs that inhibit COX isoforms directly prevent the death of motor neurons in enriched 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176562 15081582 235371 17610 9605 PTGS2 COX COX 7 0.3 This suggests that the motor neurons activate COX during an injury and the mechanisms of protection by COX 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176563 15081582 235371 17610 9605 PTGS2 COX COX 17 0.3 COX during an injury and the mechanisms of protection by COX inhibitors in mixed culture or in vivo is not mediated 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176564 15081582 235372 20996 11179 SOD1 SOD1 mSOD1 3 1.4 In the transgenic mSOD1 mouse the nonselective COX inhibitor acetylsalicylate delays the appearance of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176565 15081582 235372 17610 9605 PTGS2 COX COX 7 0.3 In the transgenic mSOD1 mouse the nonselective COX inhibitor acetylsalicylate delays the appearance of motor deficits ( Barneoud 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176566 15081582 235373 17610 9605 PTGS2 COX-2 COX-2 8 3.8 This delayed onset is recapitulated when the selective COX-2 inhibitor nimesulide is administered prophylactically in these mice ( Pompl 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176567 15081582 235375 17610 9605 PTGS2 COX-2 COX-2 6 3.8 Treatment with Celecoxib a different selective COX-2 inhibitor also prolongs survival in the mSOD1 mouse model of 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176568 15081582 235375 20996 11179 SOD1 SOD1 mSOD1 13 1.4 a different selective COX-2 inhibitor also prolongs survival in the mSOD1 mouse model of ALS ( Drachman et al. 2002 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176569 15081582 235375 20996 11179 SOD1 ALS ALS 17 1.4 inhibitor also prolongs survival in the mSOD1 mouse model of ALS ( Drachman et al. 2002 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176570 15081582 235377 17610 9605 PTGS2 COX-2 COX-2 9 3.8 It seems that neuroinflammation proceeds albeit more slowly in COX-2 inhibitor-treated animals possibly through the slower microglial COX-1 upregulation and 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176571 15081582 235377 17609 9604 PTGS1 COX-1 COX-1 17 1.3 slowly in COX-2 inhibitor-treated animals possibly through the slower microglial COX-1 upregulation and likely through multiple additional regulatory mechanisms 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176572 15081582 235378 17610 9605 PTGS2 COX-2 COX-2 6 3.8 Experiments that demonstrate protective abilities of COX-2 inhibition imply that COX-2 activation contributes to neuronal vulnerability and 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176573 15081582 235378 17610 9605 PTGS2 COX-2 COX-2 10 3.8 Experiments that demonstrate protective abilities of COX-2 inhibition imply that COX-2 activation contributes to neuronal vulnerability and apoptosis by an undefined 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176574 15081582 235379 17610 9605 PTGS2 COX COX-dependent 5 0.0 It may be that the COX-dependent production of reactive oxygen species during the peroxidase step of 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 176575 15081582 235380 18723 10261 ROS1 ROS ROS 3 0.0 Reactive oxygen species (ROS) ROS that are produced downstream of exposure to NMDA can cause 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176576 15081582 235381 17610 9605 PTGS2 COX COX 21 0.3 not known whether the amount of ROS produced by the COX enzyme is sufficient to cause neuronal death 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176577 15081582 235381 18723 10261 ROS1 ROS ROS 2 0.0 Yet NMDA-induced ROS are produced from multiple sources and it is not known 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176578 15081582 235381 18723 10261 ROS1 ROS ROS 17 0.0 sources and it is not known whether the amount of ROS produced by the COX enzyme is sufficient to cause neuronal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176579 15081582 235382 17610 9605 PTGS2 COX-2 COX-2 9 3.8 In addition some of the prostaglandin products of the COX-2 enzyme cause direct damage to neurons as well as act 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176580 15081582 235384 17610 9605 PTGS2 COX-2 COX-2 6 3.8 It is clear that neuroinflammation particularly COX-2 upregulation and prostaglandin production plays a significant role in neurodegenerative 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176581 15081582 235384 20996 11179 SOD1 ALS ALS 20 1.4 production plays a significant role in neurodegenerative disorders such as ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176582 15081582 235385 20996 11179 SOD1 ALS ALS 1 1.4 In ALS however the link between the pathology of the disease and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176583 15081582 235386 17610 9605 PTGS2 COX-2 COX-2 4 3.8 It seems likely that COX-2 inhibitors can delay the progression of symptoms and clinical studies 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176584 15081582 235387 20996 11179 SOD1 ALS ALS 7 1.4 Although treatment of neurodegenerative diseases such as ALS with COX-2 inhibitors is likely to produce some symptomatic benefit 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176585 15081582 235387 17610 9605 PTGS2 COX-2 COX-2 9 3.8 Although treatment of neurodegenerative diseases such as ALS with COX-2 inhibitors is likely to produce some symptomatic benefit it is 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176586 15081582 235388 17610 9605 PTGS2 COX-2 COX-2 21 3.8 activate NF-_amp_#x3ba B leading to a paradoxical activation of the COX-2 enzyme that is clearly a problem for this therapeutic approach 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176587 15081582 235389 17610 9605 PTGS2 COX-2 COX-2 21 3.8 prostaglandins that feedback on NF-_amp_#x3ba B to regulate transcription of COX-2 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176588 15081582 235390 17610 9605 PTGS2 COX-2 COX-2 5 3.8 Certain downstream products of the COX-2 enzyme are pro-apoptotic while others are neuroprotective 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176589 15081582 235391 17610 9605 PTGS2 COX-2 COX-2 1 3.8 Inhibiting COX-2 will block both the neurodegenerative and neuroprotective products of this 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176590 15081582 235392 17610 9605 PTGS2 COX-2 COX-2 15 3.8 in the development of future therapies rather than broadly targeting COX-2 or even further upstream at the level of NF-_amp_#x3ba B 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176591 15081582 235392 17610 9605 PTGS2 COX-2 COX-2 32 3.8 of NF-_amp_#x3ba B to target specific prostaglandin synthases downstream of COX-2 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 176592 15081582 235396 20996 11179 SOD1 ALS ALS 22 1.4 also stop the progressive loss of motor neurons in the ALS patient 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000767671373411518<>ScoreDetail__5468|IGFALS|0.00028997100289971__11179|SOD1|0.000767671373411518__ 0 0 0 0 0 176593 15081582 235398 17610 9605 PTGS2 COX COX 8 0.3 Thorough understanding of the individual roles of prostaglandins COX isoforms and neuroprotective mechanisms of COX inhibitors are essential to 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 176594 15081582 235398 17610 9605 PTGS2 COX COX 14 0.3 individual roles of prostaglandins COX isoforms and neuroprotective mechanisms of COX inhibitors are essential to further these therapeutic developments 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 169750 15210305 227134 20996 11179 SOD1 ALS ALS 6 4.1 Research efforts in amyotrophic lateral sclerosis (ALS) ALS have not yet provided a comprehensive explanation of the disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169751 15210305 227136 20996 11179 SOD1 ALS ALS 14 4.1 significantly improved our understanding of the molecular changes occurring in ALS although its limitations in the detection of low-abundance transcripts in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169752 15210305 227137 20996 11179 SOD1 ALS ALS 16 4.1 on an expression study in post-mortem spinal cord from sporadic ALS individuals will be discussed in light of recently published data 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169753 15210305 227139 20996 11179 SOD1 ALS ALS 8 4.1 Through the analysis of the information arising from ALS post-mortem and animal model tissues studies we have identified a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169754 15210305 227141 20996 11179 SOD1 ALS ALS 4 4.1 Introduction molecular studies on ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169755 15210305 227142 20996 11179 SOD1 ALS ALS 19 4.1 shed light on the pathogenesis of amyotrophic lateral sclerosis (ALS) ALS which include the significant findings that have arisen in the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169756 15210305 227143 20996 11179 SOD1 ALS ALS 0 4.1 ALS can be inherited as an autosomal dominant trait in a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169757 15210305 227144 20996 11179 SOD1 ALS ALS 1 4.1 Familial ALS (FALS) FALS is a heterogeneous entity 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169758 15210305 227146 20996 11179 SOD1 ALS ALS 2 4.1 The first ALS locus (ALS1) ALS1 to be identified on chromosome 21 contains 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169759 15210305 227146 20996 11179 SOD1 ALS1 ALS1 4 2.9 The first ALS locus (ALS1) ALS1 to be identified on chromosome 21 contains the cytosolic copper_amp_#x2013 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169760 15210305 227146 20996 11179 SOD1 SOD1 SOD1 17 6.9 chromosome 21 contains the cytosolic copper_amp_#x2013 zinc superoxide dismutase (SOD1) SOD1 gene which has been found to harbour at least 100 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169761 15210305 227147 20996 11179 SOD1 ALS ALS 15 4.1 been identified for the classical form of adult-onset autosomal dominant ALS but two new loci have been reported the first of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169762 15210305 227150 622 443 ALS2 ALS2 ALS2 8 1.5 In the case of the chromosome 2 locus (ALS2), ALS2 mutations in a putative GTPase (the the alsin gene have 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169763 15210305 227150 20996 11179 SOD1 ALS ALS 28 4.1 been found in a juvenile onset rare recessive form of ALS characterized by a predominant spastic paraparesis 33 and 112 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169764 15210305 227152 23910 12680 VEGFA VEGF VEGF 9 2.8 The potential role of the vascular endothelial growth gene (VEGF) VEGF as a risk/causitive risk causitive factor in ALS has been 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169765 15210305 227152 20996 11179 SOD1 ALS ALS 15 4.1 gene (VEGF) VEGF as a risk/causitive risk causitive factor in ALS has been recently evaluated through extensive genotyping in patients and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169766 15210305 227152 20996 11179 SOD1 ALS ALS 37 4.1 populations and using expression analysis in an animal model of ALS and post-mortem tissue from affected individuals 31 50 and 74 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169767 15210305 227153 23910 12680 VEGFA VEGF VEGF 0 2.8 VEGF induction occurs following the binding of hypoxia-inducible factors to the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169768 15210305 227154 23910 12680 VEGFA VEGF VEGF 0 2.8 VEGF coding region analysis has failed to identify mutations in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169769 15210305 227154 20996 11179 SOD1 ALS ALS 10 4.1 VEGF coding region analysis has failed to identify mutations in ALS patients but further genotyping of Swedish Belgian and English patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169770 15210305 227154 23910 12680 VEGFA VEGF VEGF 25 2.8 of Swedish Belgian and English patients has revealed a specific VEGF haplotype in the promoter region which is associated with a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169771 15210305 227154 20996 11179 SOD1 ALS ALS 41 4.1 which is associated with a 1.8 times greater risk of ALS and with lowered circulating VEGF levels in vivo 31 and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169772 15210305 227154 23910 12680 VEGFA VEGF VEGF 46 2.8 1.8 times greater risk of ALS and with lowered circulating VEGF levels in vivo 31 and 50 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169773 15210305 227155 20996 11179 SOD1 ALS ALS 13 4.1 have emerged from the analysis of potential risk factors in ALS such as the neurofilament heavy subunit 25 the apolipoprotein E 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169774 15210305 227155 20478 11117 SMN1 SMN SMN 35 0.6 apolipoprotein E allele 4 71 the gene-survival motor neuron (SMN) SMN and neuronal apoptosis inhibitory protein (NAIP) NAIP 79 1 JUMiner_v2.2 1 2 UserEdit 0 2 6510 TotalCon:3<>6510|STMN1|3925|Complete__11117|SMN1|6606|Complete__11164|SNRPN|6638|Complete__<>AvaiableGeneRif=3<>BEST:6510|STMN1|0.00124258466838137<>ScoreDetail__11117|SMN1|0.000835550050902403__11164|SNRPN|0.000636246962125556__6510|STMN1|0.00124258466838137__ 1 1 0 0 0 169775 15210305 227155 14064 7634 NAIP NAIP NAIP 41 0.6 motor neuron (SMN) SMN and neuronal apoptosis inhibitory protein (NAIP) NAIP 79 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169776 15210305 227156 4649 2169 CNTF CNTF CNTF 4 1.9 Recently Ciliary Neurotrophic factor (CNTF) CNTF has been proposed as a modifier gene since the rare 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169777 15210305 227156 20996 11179 SOD1 SOD1 SOD1 30 6.9 age of onset of disease in FALS cases carrying a SOD1 mutation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169778 15210305 227157 4649 2169 CNTF CNTF CNTF-deficient 2 1.9 Similarly when CNTF-deficient mice are crossed with SOD1 G93A transgenic mice an earlier 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169779 15210305 227157 20996 11179 SOD1 SOD1 SOD1 7 6.9 Similarly when CNTF-deficient mice are crossed with SOD1 G93A transgenic mice an earlier age of onset has been 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169780 15210305 227158 20996 11179 SOD1 ALS ALS 17 4.1 by the disease has represented an alternative research strategy in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169781 15210305 227159 20996 11179 SOD1 ALS ALS 26 4.1 proteins and enzyme activity in spinal cord and cortex from ALS individuals 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169782 15210305 227163 20996 11179 SOD1 ALS ALS 18 4.1 the main findings obtained through traditional gene expression studies in ALS affected tissues and describe the results of large-scale gene expression 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169783 15210305 227163 20996 11179 SOD1 ALS ALS 42 4.1 spinal cord from individuals affected by the sporadic form of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169784 15210305 227166 20996 11179 SOD1 ALS ALS 12 4.1 is to extrapolate significant information about molecular pathways involved in ALS pathogenesis and their importance in different phases of disease progression 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169785 15210305 227182 19327 30369 SAGE1 SAGE SAGE 12 1.0 hybridization (SH) SH and serial analysis of gene expression (SAGE) SAGE allow the comparison of a large number of mRNAs at 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 169786 15210305 227192 19327 30369 SAGE1 SAGE SAGE 17 1.0 rat hippocampus comparing the results to baseline data obtained from SAGE expression analysis on the same tissue estimates that Affymetrix arrays 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 169787 15210305 227198 20233 10986 SLC25A16 GDA GDA 9 0.6 A traditional membrane-based array technology the Gene Discovery Array (GDA) GDA filter is the array format utilized in a study of 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>4212|GDA|9615|Complete__10986|SLC25A16|8034|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 169788 15210305 227198 20996 11179 SOD1 ALS ALS 23 4.1 array format utilized in a study of gene expression in ALS spinal cord study discussed in this paper 60 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169789 15210305 227200 20233 10986 SLC25A16 GDA GDA 1 0.6 The GDA filter is a low-cost alternative to the recently developed microarrays 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>4212|GDA|9615|Complete__10986|SLC25A16|8034|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 169790 15210305 227202 20996 11179 SOD1 ALS ALS 25 4.1 expression studies undertaken in spinal cord tissue from individuals with ALS compared to normal controls 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169791 15210305 227204 20996 11179 SOD1 ALS ALS 3 4.1 Transcriptional analysis in ALS spinal cord single mRNA studies and gene array screening 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169792 15210305 227205 20996 11179 SOD1 ALS ALS 4 4.1 Gene expression studies in ALS have targeted tissues known to be functionally involved and those 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169793 15210305 227206 20996 11179 SOD1 ALS ALS 1 4.1 Both ALS post-mortem tissue and tissues taken from animal models (G93 G93 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169794 15210305 227206 20996 11179 SOD1 SOD1 SOD1 11 6.9 post-mortem tissue and tissues taken from animal models (G93 G93 SOD1 transgenic mouse of ALS have been investigated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169795 15210305 227206 20996 11179 SOD1 ALS ALS 15 4.1 taken from animal models (G93 G93 SOD1 transgenic mouse of ALS have been investigated 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169796 15210305 227209 20996 11179 SOD1 ALS ALS 18 4.1 under five main headings which cover pathogenic mechanisms implicated in ALS pathogenesis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169797 15210305 227212 20996 11179 SOD1 ALS ALS 39 4.1 analysis of spinal cord tissues from both sporadic and familial ALS individuals and from healthy controls 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169798 15210305 227215 20996 11179 SOD1 SOD1 SOD1 4 6.9 With the discovery of SOD1 gene mutations oxidative stress has gained momentum as a major 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169799 15210305 227215 20996 11179 SOD1 ALS ALS 17 4.1 oxidative stress has gained momentum as a major factor in ALS pathogenesis 90 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169800 15210305 227216 20996 11179 SOD1 SOD1 SOD1 2 6.9 The cytosolic SOD1 protein has a widespread expression in different human tissues and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169801 15210305 227217 20996 11179 SOD1 SOD1 SOD1 9 6.9 Human motor neurones show high levels of expression of SOD1 proteins compared to others neurones and this may reflect a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169802 15210305 227220 20996 11179 SOD1 SOD1 SOD1 5 6.9 It has been proposed that SOD1 may be crtical for motor neurones in stressful conditions but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169803 15210305 227222 20996 11179 SOD1 ALS ALS 1 4.1 In ALS prolonged synaptic activation by glutamate could trigger neuronal cell damage 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169804 15210305 227223 20017 10940 SLC1A2 EAAT2 EAAT2 16 1.3 receptors and of the excitatory amino acid transporter 2 (EAAT2) EAAT2 (which which is involved in the removal of glutamate from 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169805 15210305 227224 20996 11179 SOD1 ALS ALS 4 4.1 The array-based analysis of ALS spinal cord using a GDA filter format has also confirmed 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169806 15210305 227224 20233 10986 SLC25A16 GDA GDA 9 0.6 The array-based analysis of ALS spinal cord using a GDA filter format has also confirmed a pattern of marked differential 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>4212|GDA|9615|Complete__10986|SLC25A16|8034|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 169807 15210305 227225 7643 3769 FMO1 FMO1 FMO1 23 0.9 events include thioredoxin lysyl oxidase (LO), LO flavin-containing monooxygenase (FMO1), FMO1 interleukin I receptor accessory protein (IL-1RAcP) IL-1RAcP and a transcript 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169808 15210305 227225 10446 5995 IL1RAP IL-1RAcP IL-1RAcP 29 1.3 flavin-containing monooxygenase (FMO1), FMO1 interleukin I receptor accessory protein (IL-1RAcP) IL-1RAcP and a transcript representing a possible 14-3-3 spinal-cord isoform 59 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169809 15210305 227226 20996 11179 SOD1 ALS ALS 16 4.1 powerful antioxidant function counteracting the copper-catalysed oxidation of proteins in ALS tissue 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169810 15210305 227228 4682 2197 COL1A1 collagen collagen 14 0.3 copper-dependent enzyme that catalyses the synthesis reaction of hydroxylysine in collagen biosynthesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169811 15210305 227230 20996 11179 SOD1 ALS ALS 9 4.1 Flavin-containing monooxygenase (FMO) FMO found to be significantly down-regulated in ALS spinal cord exerts a powerful intrinsic protective action against oxidative 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169812 15210305 227231 20996 11179 SOD1 ALS ALS 23 4.1 to be markedly up-regulated in spinal cord from individuals with ALS 59 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169813 15210305 227234 22710 12017 TPR TPR TPR 8 0.6 A transcript identical to the ubiquitous tetratricopeptide repeat (TPR) TPR motif (Y Y isoform showed the highest level of differential 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 169814 15210305 227234 20233 10986 SLC25A16 GDA GDA 22 0.6 showed the highest level of differential gene expression in the GDA array study 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>4212|GDA|9615|Complete__10986|SLC25A16|8034|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 169815 15210305 227235 22710 12017 TPR TPR TPR 1 0.6 The TPR motif facilitates protein_amp_#x2013 protein interaction and the assembly of multiprotein 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 169816 15210305 227236 22710 12017 TPR TPR TPR-containing 0 1.1 TPR-containing mRNAs share common structural and functional properties with 14-3-3 proteins 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 169817 15210305 227237 22710 12017 TPR TPR TPR 0 0.6 TPR motifs are also involved in processes such as transcription control 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 169818 15210305 227239 20996 11179 SOD1 ALS ALS 10 4.1 Altered patterns of NF phosphorylation have also been documented in ALS 47 and 104 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169819 15210305 227240 20996 11179 SOD1 SOD1 SOD1 11 6.9 slowing of axonal transport is an important feature in mutant SOD1 mice 111 where NF aggregates are detected which affect transport 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169820 15210305 227241 20996 11179 SOD1 ALS ALS 7 4.1 Indirect evidence of nitration of neurofilaments in ALS spinal cord is indicated by elevated levels of 3-nitrotyrosine and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169821 15210305 227242 8254 4235 GFAP GFAP GFAP 0 0.6 GFAP up-regulation is not uncommonly seen in expression studies reflecting reactive 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169822 15210305 227243 20996 11179 SOD1 ALS ALS 23 4.1 the degeneration of the motor neurones in spinal cord from ALS individuals 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169823 15210305 227245 20996 11179 SOD1 ALS ALS-related 0 2.9 ALS-related differential expression has been identified in tissues other than those 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169824 15210305 227247 20996 11179 SOD1 ALS ALS 31 4.1 procollagen (PIIIP) PIIIP in serum and skin of patients with ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169825 15210305 227248 20996 11179 SOD1 ALS ALS 7 4.1 The PIIIP immunoreactivity in these tissues from ALS individuals was significantly higher than in controls and was markedly 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169826 15210305 227249 4682 2197 COL1A1 collagen collagen 7 0.3 The relationship between the metabolic alteration of collagen taking place in the skin and serum of ALS patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169827 15210305 227249 20996 11179 SOD1 ALS ALS 16 4.1 of collagen taking place in the skin and serum of ALS patients and the neurodegenerative changes targeting the motor neurones population 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169828 15210305 227250 23910 12680 VEGFA VEGF VEGF 3 2.8 An increase of VEGF levels in serum but not in homogenates of spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169829 15210305 227250 20996 11179 SOD1 ALS ALS 16 4.1 serum but not in homogenates of spinal cord from sporadic ALS patients indicates that hypoxia may play a part during the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169830 15210305 227250 23910 12680 VEGFA VEGF VEGF 35 2.8 during the course of the disease process generating a time-dependent VEGF tissue response 74 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169831 15210305 227256 20996 11179 SOD1 ALS ALS 14 4.1 in human neuroblastoma cell lines by anti-Fas antibody-containing sera from ALS patients whereas this was less convincingly obtained using sera from 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169832 15210305 227257 20996 11179 SOD1 ALS ALS 10 4.1 Other authors have failed to demonstrate evidence of apoptosis in ALS 36 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169833 15210305 227258 20996 11179 SOD1 ALS ALS 38 4.1 in dorsal and ventral horns of autopsied spinal cord from ALS cases 108 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169834 15210305 227259 10824 6204 JUN c-Jun c-jun 9 2.4 Immunohistochemical expression of a number of gene candidates including c-jun JNK/SAPK JNK SAPK (a a kinase that exerts a stress-related 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169835 15210305 227259 12349 6881 MAPK8 JNK JNK 10 0.3 expression of a number of gene candidates including c-jun JNK/SAPK JNK SAPK (a a kinase that exerts a stress-related activation of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169836 15210305 227259 12354 6886 MAPK9 SAPK SAPK 10 1.3 of a number of gene candidates including c-jun JNK/SAPK JNK SAPK (a a kinase that exerts a stress-related activation of c-jun 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169837 15210305 227259 10824 6204 JUN c-Jun c-jun 19 2.4 SAPK (a a kinase that exerts a stress-related activation of c-jun and NF-kappa B a transcription factor induced by oxidative injury 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169838 15210305 227260 12349 6881 MAPK8 JNK JNK 1 0.3 The JNK/SAPK-c-Jun JNK SAPK-c-Jun pathway was found to be markedly up-regulated 67 in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169839 15210305 227260 20996 11179 SOD1 ALS ALS 13 4.1 SAPK-c-Jun pathway was found to be markedly up-regulated 67 in ALS spinal cord astrocytes together with NF-kappa B whereas motor neurones 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169840 15210305 227261 20996 11179 SOD1 ALS ALS 14 4.1 idea that astrocytes are key players in the pathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169841 15210305 227262 20996 11179 SOD1 ALS ALS 22 4.1 to be differentially regulated using large-scale gene expression studies in ALS spinal cord 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169842 15210305 227265 20996 11179 SOD1 ALS ALS 12 4.1 selective pro-apoptotic activity targeting the glial and neuronal cells in ALS spinal cord may be suggested in light of these expression 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169843 15210305 227266 5063 2482 CSTB STFB STFB 14 4.6 was found to have a high homology with Stefin B STFB also called cystatin B (CSTB)], CSTB which is a member 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169844 15210305 227266 5063 2482 CSTB CSTB CSTB 19 4.6 homology with Stefin B STFB also called cystatin B (CSTB)], CSTB which is a member of the superfamily of non-caspase cysteine 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169845 15210305 227267 5063 2482 CSTB EPM1 EPM1 12 4.6 of progressive myoclonus epilepsy of the Unverricht_amp_#x2013 Lundborg type (EPM1) EPM1 are caused by mutations (mostly mostly an expansion of a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169846 15210305 227268 5063 2482 CSTB EPM1 EPM1 0 4.6 EPM1 is an autosomal recessive disorder characterized by seizures myoclonus and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169847 15210305 227269 5063 2482 CSTB EPM1 EPM1 16 4.6 cystatin B mRNA down-regulation in various tissues from patients with EPM1 49 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169848 15210305 227271 20996 11179 SOD1 ALS ALS 8 4.1 The importance of this anti-apoptotic agent over-expressed in ALS spinal cord and down-regulated in a hereditary form of epilepsy 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169849 15210305 227272 5063 2482 CSTB EPM1 EPM1 28 4.6 spinal cord involvement such as spinal or segmental myoclonus in EPM1 and paralysis with muscle wasting in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169850 15210305 227272 20996 11179 SOD1 ALS ALS 35 4.1 segmental myoclonus in EPM1 and paralysis with muscle wasting in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169851 15210305 227276 20996 11179 SOD1 ALS ALS 4 4.1 Gene expression analysis in ALS spinal cord has revealed the differential regulation of transcripts contributing 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169852 15210305 227276 20996 11179 SOD1 ALS ALS 40 4.1 silenced_amp_#x201d in spinal cord from post-mortem and animal model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169853 15210305 227277 4649 2169 CNTF CNTF CNTF 0 1.9 CNTF initially reported as a potent survival factor in spinal motor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169854 15210305 227278 4649 2169 CNTF CNTF CNTF 0 1.9 CNTF expression was down-regulated in the lateral corticospinal tracts of spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169855 15210305 227278 20996 11179 SOD1 ALS ALS 13 4.1 down-regulated in the lateral corticospinal tracts of spinal cord from ALS patients compared to control particularly in those patients exhibiting a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169856 15210305 227278 4649 2169 CNTF CNTF CNTF 25 1.9 compared to control particularly in those patients exhibiting a specific CNTF null allele 77 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169857 15210305 227279 4649 2169 CNTF CNTF CNTF 4 1.9 However genotyping of the CNTF receptor alpha (CNTFR-alpha) CNTFR-alpha has failed to show any significant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169858 15210305 227279 20996 11179 SOD1 ALS ALS 23 4.1 significant association between allelic variants of this gene and familial ALS (FALS) FALS 44 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169859 15210305 227280 20996 11179 SOD1 ALS ALS 10 4.1 A marked increase in CNTFR-alpha mRNA expression was found in ALS spinal cord whereas the same transcript showed little or no 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169860 15210305 227280 20996 11179 SOD1 ALS ALS 23 4.1 whereas the same transcript showed little or no expression in ALS motor cortex with no differences seen between ALS and control 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169861 15210305 227280 20996 11179 SOD1 ALS ALS 31 4.1 expression in ALS motor cortex with no differences seen between ALS and control tissues 22 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169862 15210305 227281 7521 3665 FGF1 AFGF aFGF 4 2.2 Acidic fibroblast growth factor (aFGF) aFGF has been investigated in anterior horn cells of spinal cord 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169863 15210305 227281 20996 11179 SOD1 ALS ALS 16 4.1 been investigated in anterior horn cells of spinal cord from ALS patients using reverse transcription polymerase chain reaction (RT-PCR) RT-PCR and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169864 15210305 227282 1746 3581 BPTF FAC1 FAC1 0 1.0 FAC1 a protein known to play a key role in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169865 15210305 227282 20996 11179 SOD1 ALS ALS 35 4.1 spinal cord but it became detectable in motor neurones of ALS patients with a further up-regulation during disease progression 70 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169866 15210305 227283 20996 11179 SOD1 ALS ALS 9 4.1 The same pattern of up-regulation in motor neurones from ALS spinal cord applies to growth-associated protein 43 (GAP43), GAP43 a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169867 15210305 227283 8117 4140 GAP43 GAP43 GAP43 17 0.6 from ALS spinal cord applies to growth-associated protein 43 (GAP43), GAP43 a phosphoprotein which is expressed during neurite elongation 42 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169868 15210305 227284 20996 11179 SOD1 ALS ALS 39 4.1 androgens and steroids were seen in post-mortem spinal cord from ALS individuals and from animal models of the disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169869 15210305 227285 951 644 AR SBMA SBMA 19 1.6 motor system is exemplified by spinal bulbar muscular atrophy (SBMA), SBMA a condition in which a clinical picture of motor neurone 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169870 15210305 227285 20996 11179 SOD1 ALS ALS 32 4.1 in which a clinical picture of motor neurone degeneration resembling ALS and clinical signs of androgen partial insensitivity (gynecomastia) gynecomastia coexist 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169871 15210305 227287 20996 11179 SOD1 ALS ALS 11 4.1 was found to be over-expressed in spinal cord tissues from ALS individuals 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169872 15210305 227290 9601 14922 HRASLS H-REV107 H-REV107-like 9 2.3 Another hormone sensitive transcript with high homology to rat H-REV107-like protein was found to be significantly up-regulated in ALS spinal 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169873 15210305 227290 20996 11179 SOD1 ALS ALS 18 4.1 rat H-REV107-like protein was found to be significantly up-regulated in ALS spinal cord 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169874 15210305 227291 9600 5173 HRAS HRAS HRAS 21 0.3 II tumour suppressor as shown by its reversible down-regulation in HRAS transformed cell line 99 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169875 15210305 227292 18105 9919 RBP1 CRBP1 CRBP1 3 3.1 Cellular retinol-binding protein1 (CRBP1) CRBP1 showed a marked up-regulation in ALS spinal cord 60 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169876 15210305 227292 20996 11179 SOD1 ALS ALS 9 4.1 Cellular retinol-binding protein1 (CRBP1) CRBP1 showed a marked up-regulation in ALS spinal cord 60 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169877 15210305 227295 18105 9919 RBP1 CRBP CRBP 3 3.1 Cellular retinoid-binding proteins (CRBP) CRBP have a privileged distribution in the ventral region (motor motor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169878 15210305 227297 18723 10261 ROS1 ROS ROS 8 0.3 Retinoid acid (RA) RA reduces neuronal reactive oxygen species (ROS) ROS content and enhances SOD1 protein levels during staurosporine-induced apoptosis in 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 169879 15210305 227297 20996 11179 SOD1 SOD1 SOD1 12 6.9 reduces neuronal reactive oxygen species (ROS) ROS content and enhances SOD1 protein levels during staurosporine-induced apoptosis in primary cultures from neonatal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169880 15210305 227298 14373 7808 NGF NGF NGF 8 0.6 In addition RA potentiates the protective effect of NGF in a model of stautosporine-induced apoptosis in cultured chick neurones 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169881 15210305 227300 18105 9919 RBP1 CRBP1 CRBP1 5 3.1 The marked up-regulation of the CRBP1 in ALS spinal cord and of the retinoid receptor subunit 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169882 15210305 227300 20996 11179 SOD1 ALS ALS 7 4.1 The marked up-regulation of the CRBP1 in ALS spinal cord and of the retinoid receptor subunit in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169883 15210305 227300 20996 11179 SOD1 ALS ALS 17 4.1 ALS spinal cord and of the retinoid receptor subunit in ALS transgenic mice may be a response to a _amp_#x201c loss 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169884 15210305 227302 20996 11179 SOD1 ALS ALS 13 4.1 an involvement of these molecular pathways in the pathogenesis of ALS may find some support in the study by Yoshihara et 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169885 15210305 227302 4911 2345 CREB1 CREB CREB-binding 35 2.1 et al 115 which shows a significant up-regulation of a CREB-binding protein in the G93A transgenic (TG) TG animal model 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169886 15210305 227304 20996 11179 SOD1 ALS ALS 8 4.1 In addition the over-expression of hormone-sensitive transcripts in ALS spinal cord such as granulin may be related to the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169887 15210305 227306 20996 11179 SOD1 ALS ALS 34 4.1 us to reveal further important clues in the pathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169888 15210305 227309 20996 11179 SOD1 ALS ALS 9 4.1 The role of tissue inflammation in the development of ALS pathology has been widely debated 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169889 15210305 227310 20996 11179 SOD1 ALS ALS 12 4.1 of any consistent response to immunosuppressive and immuno-modulatory treatments in ALS is not consistent with autoimmunity playing a major role in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169890 15210305 227311 20996 11179 SOD1 ALS ALS 21 4.1 of glutamate-mediated excitotoxicity may trigger a tissue inflammatory response in ALS 12 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169891 15210305 227314 3758 10618 CCL2 MCP-1 MCP-1 17 1.6 beta deposition activates astrocytes and oligodendrocytes to produce chemokines (MCP-1 MCP-1 and RANTES which act as potent in vitro microglial and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169892 15210305 227314 3766 10632 CCL5 RANTES RANTES 19 1.6 activates astrocytes and oligodendrocytes to produce chemokines (MCP-1 MCP-1 and RANTES which act as potent in vitro microglial and macrophage chemoattractants 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169893 15210305 227315 18723 10261 ROS1 ROS ROS 11 0.3 stimulates microglia to secrete cytokines and reactive oxygen species (ROS), ROS which can induce neuronal damage 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 169894 15210305 227316 20996 11179 SOD1 ALS ALS 13 4.1 T cells adhering to postcapillary venules are frequently observed in ALS and in mouse models of the disease 63 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169895 15210305 227317 20996 11179 SOD1 ALS ALS 18 4.1 over-expression of transcripts associated with immune and inflammatory response within ALS spinal cord and in the activation of the complement system 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169896 15210305 227318 2033 1242 C1QB C1QB C1qB 0 0.3 C1qB clusterin (apoJ) apoJ and the T-cell receptor (TCR) TCR transcript 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169897 15210305 227318 4560 2095 CLU APOJ apoJ 2 2.0 C1qB clusterin (apoJ) apoJ and the T-cell receptor (TCR) TCR transcript have been found 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169898 15210305 227318 20996 11179 SOD1 ALS ALS 19 4.1 have been found to be markedly up-regulated in areas of ALS spinal cord undergoing degeneration 30 and 80 whereas a study 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169899 15210305 227318 20996 11179 SOD1 ALS ALS 43 4.1 kinase-5 (cdk-5) cdk-5 regional expression identified a significant up-regulation in ALS affected motor neurones 6 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169900 15210305 227319 17610 9605 PTGS2 COX-2 COX-2 0 2.0 COX-2 and CD11B (a a specific marker of microglia activation have 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169901 15210305 227319 10731 6149 ITGAM CD11B CD11B 2 1.0 COX-2 and CD11B (a a specific marker of microglia activation have been reported 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169902 15210305 227319 20996 11179 SOD1 ALS ALS 16 4.1 of microglia activation have been reported to be up-regulated in ALS spinal cord tissue 113 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169903 15210305 227320 17610 9605 PTGS2 COX-2 COX-2 4 2.0 The significant up-regulation of COX-2 in ALS spinal cord compared to control tissues including patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169904 15210305 227320 20996 11179 SOD1 ALS ALS 6 4.1 The significant up-regulation of COX-2 in ALS spinal cord compared to control tissues including patients affected by 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169905 15210305 227320 20996 11179 SOD1 ALS ALS 42 4.1 observation of a central role of an inflammatory response in ALS pathogenesis 113 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169906 15210305 227321 17610 9605 PTGS2 COX-2 COX-2 0 2.0 COX-2 mRNA up-regulation was restricted to pathologically affected tissue and this 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169907 15210305 227321 17610 9605 PTGS2 COX-2 COX-2 15 2.0 to pathologically affected tissue and this was accompanied by increased COX-2 protein levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169908 15210305 227322 20233 10986 SLC25A16 GDA GDA 1 0.6 The GDA array study has further contributed to the identification of differentially 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>4212|GDA|9615|Complete__10986|SLC25A16|8034|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 169909 15210305 227323 10446 5995 IL1RAP IL-1RAcP IL-1RAcP 5 1.3 Interleukin I receptor accessory protein (IL-1RAcP) IL-1RAcP mRNA markedly over-expressed in ALS spinal cord is a trans-membrane 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169910 15210305 227323 20996 11179 SOD1 ALS ALS 10 4.1 I receptor accessory protein (IL-1RAcP) IL-1RAcP mRNA markedly over-expressed in ALS spinal cord is a trans-membrane protein belonging to a receptor 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169911 15210305 227323 10437 5992 IL1B IL-1 IL-1 29 1.3 receptor complex which binds to the pro-inflammatory protein interleukin-1 (IL-1) IL-1 14 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169912 15210305 227324 10446 5995 IL1RAP IL-1RAcP IL-1RAcP 0 1.3 IL-1RAcP has also been found to be up-regulated in spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169913 15210305 227324 20996 11179 SOD1 SOD1 SOD1 12 6.9 also been found to be up-regulated in spinal cord from SOD1 G93A transgenic mice 76 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169914 15210305 227326 20996 11179 SOD1 ALS ALS 30 4.1 reaction causing dendritic/axonal dendritic axonal and somatic degeneration closely resembling ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169915 15210305 227327 3766 10632 CCL5 RANTES RANTES 4 1.6 The small inducible cytokine (RANTES) RANTES mRNA was also found in the GDA study to be 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169916 15210305 227327 20233 10986 SLC25A16 GDA GDA 11 0.6 inducible cytokine (RANTES) RANTES mRNA was also found in the GDA study to be up-regulated in ALS spinal cord 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>4212|GDA|9615|Complete__10986|SLC25A16|8034|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 169917 15210305 227327 20996 11179 SOD1 ALS ALS 17 4.1 also found in the GDA study to be up-regulated in ALS spinal cord 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169918 15210305 227328 3865 1678 CD4 CD4 CD4 16 0.3 subfamily of chemokines that function as a pro-inflammatory chemoattractant for CD4 T cells monocytes and eosinophils and as an activator of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169919 15210305 227329 3766 10632 CCL5 RANTES RANTES 7 1.6 Like other members of the chemokine superfamily RANTES has been implicated in a number of chronic inflammatory and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169920 15210305 227332 20996 11179 SOD1 ALS ALS 3 4.1 Studies on post-mortem ALS spinal cord have hinted at a potential role for lipid 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169921 15210305 227332 20996 11179 SOD1 ALS ALS 21 4.1 role for lipid and oxysterols metabolism in the pathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169922 15210305 227333 20996 11179 SOD1 ALS ALS 12 4.1 up-regulation of cholesterol 25 hydroxylase has been identified in post-mortem ALS spinal cord 60 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169923 15210305 227336 20996 11179 SOD1 ALS ALS 13 4.1 an abnormal metabolism of cholesterol as a disease-causing factor in ALS has been strengthened further by the report of abnormalities in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169924 15210305 227336 20996 11179 SOD1 ALS ALS 33 4.1 in sphingolipid and cholesterol metabolism in the spinal cords of ALS patients and animal models of the disease based on the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169925 15210305 227339 5417 2641 CYP46A1 CYP46 CYP46 22 2.8 by a recent study on cholesterol 24-hydroxylase encoded by the CYP46 gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169926 15210305 227341 5417 2641 CYP46A1 CYP46 CYP46 1 2.8 A CYP46 polymorphism is associated with an increased beta-amyloid load in brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169927 15210305 227341 12369 6893 MAPT tau tau 20 0.8 tissues increased cerebrospinal fluid levels of beta-amyloid peptides/phosphorylated peptides phosphorylated tau protein and to a higher risk of late onset sporadic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169928 15210305 227342 14569 7897 NPC1 NPC NP-C 23 0.3 neurovisceral lipid storage disorder Niemann_amp_#x2013 Pick type C disease (NP-C) NP-C 84 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169929 15210305 227343 14569 7897 NPC1 NPC NP-C 0 0.3 NP-C is a neurodevelopmental disorder characterized by progressive neurodegeneration and lysosomal 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169930 15210305 227344 78 61 ABCD1 adrenoleukodystrophy adrenoleukodystrophy 4 1.0 A form of X-linked adrenoleukodystrophy (X-ALD) X-ALD which involves the spinal cord adrenomyeloneuropathy (AMN), AMN 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 169931 15210305 227344 78 61 ABCD1 AMN AMN 12 1.0 adrenoleukodystrophy (X-ALD) X-ALD which involves the spinal cord adrenomyeloneuropathy (AMN), AMN is another neurodegenerative disease characterized by elevated levels of saturated 1 JUMiner_v2.2 1 2 UserEdit 0 2 61 TotalCon:2<>14604|AMN|81693|Complete__61|ABCD1|215|Complete__<>AvaiableGeneRif=2<>BEST:61|ABCD1|0.000689058035943246<>ScoreDetail__14604|AMN|0.000485149686427642__61|ABCD1|0.000689058035943246__ 1 1 0 0 0 169932 15210305 227346 20996 11179 SOD1 ALS ALS 9 4.1 Spinal cord expression profiles in an animal model of ALS compared to post-mortem findings what can we learn 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169933 15210305 227349 20996 11179 SOD1 ALS ALS 1 4.1 In ALS the interpretation of the gene expression profile in post-mortem tissue 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169934 15210305 227350 20996 11179 SOD1 SOD1 SOD1 16 6.9 in spinal cord of transgenic mouse models with the G93A SOD1 gene mutation 37 76 and 115 the molecular profiling of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169935 15210305 227352 20996 11179 SOD1 SOD1 SOD1 1 6.9 In SOD1 G93A mice the timing of behavioural and pathological changes appears 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169936 15210305 227353 20996 11179 SOD1 ALS ALS 13 4.1 spinal cord from this transgenic construct is in line with ALS studies yielding a pattern of differential regulation of gene candidates 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169937 15210305 227360 18741 10289 RPA1 RPA RPAs 38 0.0 apoptosis-related genes were investigated using multiprobe ribonuclease protection assays (RPAs) RPAs in the study by Hensley et al 37 whereas the 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169938 15210305 227367 20996 11179 SOD1 ALS ALS 24 4.1 life in spinal cord from the G93A animal model of ALS which undergoes a slight decline towards the 120th day ( 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169939 15210305 227369 10436 5991 IL1A IL1A IL1alpha 11 0.3 study demonstrates the over-expression of a subset of cytokines including IL1alpha IL1beta and IL1RA at 80 days undergoing a significant increase 12 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169940 15210305 227369 10437 5992 IL1B IL1B IL1beta 12 1.3 demonstrates the over-expression of a subset of cytokines including IL1alpha IL1beta and IL1RA at 80 days undergoing a significant increase by 12 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169941 15210305 227369 10444 5993 IL1R1 IL1RA IL1RA 14 1.3 over-expression of a subset of cytokines including IL1alpha IL1beta and IL1RA at 80 days undergoing a significant increase by 120 days 1 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000604843604725064<>ScoreDetail__5993|IL1R1|0.00059381624914156__6000|IL1RN|0.000604843604725064__ 0 0 0 0 0 169942 15210305 227369 10452 6001 IL2 IL2 IL2 31 0.3 by 120 days whereas T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 are not differentially expressed at these time 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169943 15210305 227369 10456 6011 IL3 IL3 IL3 32 0.6 120 days whereas T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 are not differentially expressed at these time points 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169944 15210305 227369 10458 6014 IL4 IL4 IL4 32 0.3 120 days whereas T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 are not differentially expressed at these time points 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169945 15210305 227369 10458 6014 IL4 IL4 IL4 34 0.3 whereas T-cell derived cytokines (lymphokines) lymphokines including IL2 IL3 and IL4 are not differentially expressed at these time points 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169946 15210305 227371 20017 10940 SLC1A2 EAAT2 EAAT2 12 1.3 expression studies have highlighted the early focal loss of the EAAT2 glutamate transporter in the ventral horn of the G93A TG 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169947 15210305 227372 20017 10940 SLC1A2 EAAT2 EAAT2 11 1.3 pattern of steady increase of gliosis paralleled with a 90% EAAT2 loss in the ventral horn is also reported suggesting a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169948 15210305 227373 1576 990 BCL2 Bcl-2 Bcl-2 7 1.0 Towards the end stage of the disease Bcl-2 and Bcl-XL proteins acting as apoptosis inhibitors show reduced expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169949 15210305 227373 20996 11179 SOD1 ALS ALS 37 4.1 be up-regulated in spinal cord of the animal model of ALS 109 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169950 15210305 227375 20996 11179 SOD1 ALS ALS 5 4.1 In the animal model of ALS LO shows a steady increase at 3 and 4.5 months 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169951 15210305 227375 20996 11179 SOD1 SOD1 SOD1 35 6.9 stem cortex and in Purkinje cells of the cerebellum in SOD1 mutant animals 52 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169952 15210305 227376 20996 11179 SOD1 ALS ALS 8 4.1 The expression data from the animal model of ALS indicates that an inflammatory reaction persists throughout the disease enhanced 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169953 15210305 227379 20996 11179 SOD1 ALS ALS 25 4.1 regulated in a post-mortem expression study of spinal cord from ALS cases in adult rat motor neurones following hypoglossal nerve injury 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169954 15210305 227379 20996 11179 SOD1 SOD1 SOD1 43 6.9 hypoglossal nerve injury and in erythrocytes of FALS cases with SOD1 mutations 60 61 and 75 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169955 15210305 227380 20996 11179 SOD1 ALS ALS 11 4.1 the other hand RNAse-I which is also significantly up-regulated in ALS is known to have an anti-proliferative effect and it may 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169956 15210305 227381 9601 14922 HRASLS H-REV107 H-REV107-like 14 2.3 in the post-mortem study such as the human homologue of H-REV107-like protein are known to have an intrinsic anti-proliferative activity 41 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169957 15210305 227381 21719 11556 TAL1 TAL1 TAL-1 34 1.6 anti-proliferative activity 41 or as in the case of the TAL-1 proto-oncogene to increase cell proliferation via an anti-apoptotic effect 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169958 15210305 227382 20996 11179 SOD1 ALS ALS 8 4.1 Up-regulation of cystatin B and 14-3-3 proteins in ALS spinal cord may also be seen as an anti-apoptotic mechanism 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169959 15210305 227383 20996 11179 SOD1 ALS ALS 19 4.1 protective function has been found to be markedly down-regulated in ALS spinal cord 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169960 15210305 227385 20996 11179 SOD1 SOD1 SOD1 3 6.9 The study of SOD1 G93A transgenic mice by Olsen et al 76 identified a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169961 15210305 227386 912 613 APOE APOE ApoE 2 1.3 Apolipoprotein E (ApoE) ApoE and (to to a lesser extent Apo D gene expression 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169962 15210305 227388 6918 3562 FABP7 B-FABP B-FABP 10 2.5 include Hexosaminidase B and brain fatty acid binding protein (B-FABP), B-FABP the latter acting as a molecular scavenger binding to oxidized 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169963 15210305 227391 20996 11179 SOD1 ALS ALS 18 4.1 studies gene expression analysis in human post-mortem spinal cord from ALS individuals shows that the majority of differentially regulated transcripts serve 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169964 15210305 227394 20996 11179 SOD1 SOD1 SOD1 23 6.9 may also account for diversities in the molecular profile between SOD1 animal models and human tissue studies 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169965 15210305 227395 20996 11179 SOD1 ALS ALS 19 4.1 differentially expressed in the expression studies in human tissue from ALS individuals 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169966 15210305 227397 20996 11179 SOD1 ALS ALS 12 4.1 a recent molecular indexing and cDNA microarray analysis study on ALS spinal cord have also been included which account for a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169967 15210305 227404 20996 11179 SOD1 ALS ALS 6 4.1 In the G93A animal models of ALS clinical manifestations appear as early as 60_amp_#x2013 90 days of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169968 15210305 227407 20996 11179 SOD1 SOD1 SOD1 16 6.9 a markedly increased expression in spinal cord astrocytes of G93A SOD1 transgenic mice particularly in the early stage of disease whereas 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169969 15210305 227408 20996 11179 SOD1 ALS ALS 24 4.1 analysis in the spinal cord of the animal model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169970 15210305 227414 1372 870 ATP7B ATP7B ATP7B 0 0.0 ATP7B regulates copper uptake in the trans-Golgi network which is channeled 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169971 15210305 227416 20996 11179 SOD1 SOD1 SOD1 11 6.9 abnormal copper homeostasis may reflect the activity of the mutated SOD1 enzyme 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169972 15210305 227417 11153 6321 KIF3C KIF3C KIF3C 16 0.6 an early stage of the disease in TG mice include KIF3C which is involved in axonal transport and highlights the early 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169973 15210305 227417 20996 11179 SOD1 ALS ALS 36 4.1 early involvement of impaired axonal transport in the development of ALS 111 and LDL-r which is involved in lipid metabolism 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169974 15210305 227417 11736 6547 LDLR LDLR LDL-r 41 0.6 impaired axonal transport in the development of ALS 111 and LDL-r which is involved in lipid metabolism 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169975 15210305 227418 7526 3684 FGF6 FGF6 FGF-6 0 1.2 FGF-6 is significantly up-regulated at 80 days but its expression decreases 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169976 15210305 227421 20996 11179 SOD1 ALS ALS 6 4.1 The quest for pathogenic clues in ALS makes it a priority to understand these events in the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169977 15210305 227424 20996 11179 SOD1 ALS ALS 13 4.1 be also identified in more accessible tissue of the living ALS patients such as blood or skin providing a way of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169978 15210305 227429 20996 11179 SOD1 ALS ALS 21 4.1 candidates functionally related to the gene families highlighted in the ALS expression studies reported above 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169979 15210305 227435 20996 11179 SOD1 ALS ALS 9 4.1 This molecular picture clearly differs from the findings in ALS spinal cord where remarkable up-regulation of stress-related and cytoskeletal transcripts 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169980 15210305 227436 926 620 APP amyloid amyloid 17 1.6 of AD pathology possibly established and maintained by a significant amyloid beta deposition 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 169981 15210305 227438 926 620 APP amyloid amyloid 1 1.6 The amyloid precursor protein/presenilin-1 protein presenilin-1 (APP+PS1) APP PS1 transgenic mouse is 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 169982 15210305 227438 926 620 APP APP APP 4 0.6 The amyloid precursor protein/presenilin-1 protein presenilin-1 (APP+PS1) APP PS1 transgenic mouse is a model for amyloid deposition and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169983 15210305 227438 17461 9508 PSEN1 PS1 PS1 4 0.6 The amyloid precursor protein/presenilin-1 protein presenilin-1 (APP+PS1) APP PS1 transgenic mouse is a model for amyloid deposition and as 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 169984 15210305 227438 926 620 APP amyloid amyloid 11 1.6 presenilin-1 (APP+PS1) APP PS1 transgenic mouse is a model for amyloid deposition and as in AD the mice develop memory deficits 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 169985 15210305 227438 926 620 APP amyloid amyloid 23 1.6 and as in AD the mice develop memory deficits and amyloid deposits accumulate 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 169986 15210305 227442 9905 5438 IFNG IFN-gamma IFN-gamma 31 0.8 uninfected microglia exposed to inflammatory stimuli such as lipopolysaccharide and IFN-gamma as well as prion protein (PrP) PrP amyloid 5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169987 15210305 227442 2163 1325 C4BPA PrP PrP 37 1.3 as lipopolysaccharide and IFN-gamma as well as prion protein (PrP) PrP amyloid 5 1 JUMiner_v2.2 1 2 UserEdit 0 2 9353 TotalCon:4<>9353|PRDX2|7001|Complete__9449|PRNP|5621|Complete__47|ABCB6|10058|Complete__1325|C4BPA|722|Complete__<>AvaiableGeneRif=4<>BEST:9353|PRDX2|0.000802889290179192<>ScoreDetail__1325|C4BPA|0.000456412596987677__47|ABCB6|0.000359424920127796__9353|PRDX2|0.000802889290179192__9449|PRNP|0.000643033151108111__ 1 1 0 0 0 169988 15210305 227442 926 620 APP amyloid amyloid 38 1.6 lipopolysaccharide and IFN-gamma as well as prion protein (PrP) PrP amyloid 5 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 169989 15210305 227443 2163 1325 C4BPA PrP PrP 7 1.3 A microglia-activated phenotype is detectable even before PrP pathology is detectable in brain 1 JUMiner_v2.2 1 2 UserEdit 0 2 9353 TotalCon:4<>9353|PRDX2|7001|Complete__9449|PRNP|5621|Complete__47|ABCB6|10058|Complete__1325|C4BPA|722|Complete__<>AvaiableGeneRif=4<>BEST:9353|PRDX2|0.000802889290179192<>ScoreDetail__1325|C4BPA|0.000456412596987677__47|ABCB6|0.000359424920127796__9353|PRDX2|0.000802889290179192__9449|PRNP|0.000643033151108111__ 1 1 0 0 0 169990 15210305 227450 20996 11179 SOD1 ALS ALS 4 4.1 In contrast in the ALS studies various members of the retinoid pathways seem to be 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169991 15210305 227459 1494 936 BAD BAD BAD 28 0.3 specific apoptosis-related gene candidates such as Bcl-xl and the calcineurin-mediated BAD dephosphorylation which is known to activate the caspase 3 apoptotic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169992 15210305 227462 20996 11179 SOD1 ALS ALS 15 4.1 studies in tissues undergoing degeneration in neurological conditions such as ALS is becoming increasingly evident with the development of molecular studies 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169993 15210305 227463 19327 30369 SAGE1 SAGE SAGE 14 1.0 applied in a search for new PD molecular abnormalities using SAGE to identify potential candidate genes in substantia nigra (SN) SN 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 169994 15210305 227465 19760 445 SETX ALS4 ALS4 36 1.0 the locus on 16q 1 91 and 93 and the ALS4 locus (9q34) 9q34 for early onset dominant ALS cases 10 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169995 15210305 227465 20996 11179 SOD1 ALS ALS 43 4.1 and the ALS4 locus (9q34) 9q34 for early onset dominant ALS cases 10 in which RXR-alpha is located 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169996 15210305 227466 20996 11179 SOD1 SOD1 SOD1 10 6.9 Cystatin B was also found to be close to the SOD1 gene on chromosome 21 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 169997 15210305 227468 20996 11179 SOD1 ALS ALS 4 4.1 As reported above for ALS the two experimental approaches can yield a similar picture with 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169998 15210305 227472 20996 11179 SOD1 ALS ALS 3 4.1 A model of ALS pathogenesis from healthy motor neurones (MN) MN and glia through 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 169999 15210305 227472 20996 11179 SOD1 ALS ALS 37 4.1 genes that have been detected in spinal cord tissue from ALS cases 59 and 60 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 170000 15210305 227475 20996 11179 SOD1 SOD1 SOD1 10 6.9 Time-dependent differential gene expression in spinal cord from the G93A SOD1 gene transgenic mouse model 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 170001 15210305 227480 18741 10289 RPA1 RPA RPAs 38 0.0 apoptosis-related genes were investigated using multiprobe ribonuclease protection assays (RPAs) RPAs in the study by Hensley et al 39 whereas the 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 170002 15210305 227482 20996 11179 SOD1 ALS ALS 10 4.1 Summary of functional categories of genes that are affected in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 170003 15210305 227483 20996 11179 SOD1 ALS ALS 28 4.1 transcripts identified in the expression studies in spinal cord from ALS individuals 43 and 60 *This category includes genes involved in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000753659189285332<>ScoreDetail__5468|IGFALS|0.000600572854106994__11179|SOD1|0.000753659189285332__ 0 0 0 0 0 170004 15210305 227485 20996 11179 SOD1 SOD1 SOD1 12 6.9 spinal cord of animal model of the disease (G93A G93A SOD1 gene transgenic mouse candidate genes found to have an early 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 175686 15341181 234529 9691 5232 HSPA1A HSP HSP 30 1.4 genes termed vitagenes and including among others members of the HSP system such as HSP70 and HSP32 to detect and control 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 175687 15341181 234529 9691 5232 HSPA1A HSP70 HSP70 34 1.4 including among others members of the HSP system such as HSP70 and HSP32 to detect and control diverse forms of stress 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 175688 15341181 234530 9462 5013 HMOX1 HO-1 HO-1 8 2.4 In particular HSP32 also known as heme oxygenase-1 (HO-1), HO-1 has received considerable attention as it has been recently demonstrated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 175689 15341181 234530 9462 5013 HMOX1 HO-1 HO-1 20 2.4 received considerable attention as it has been recently demonstrated that HO-1 induction by generating the vasoactive molecule carbon monoxide and the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 175690 15341181 234531 9462 5013 HMOX1 HO-1 HO-1 5 2.4 Increasing evidence suggests that the HO-1 gene is redox-regulated and its expression appears closely related to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164416 15453089 221231 17610 9605 PTGS2 COX COX 1 0.6 Cyclooxygenase (COX) COX catalyses the first committed step in the synthesis of prostanoids 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164417 15453089 221232 17610 9605 PTGS2 COX COX 0 0.6 COX exists as constitutive and inducible isoforms 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164418 15453089 221233 17610 9605 PTGS2 COX-2 COX-2 0 4.4 COX-2 is the inducible isoform rapidly expressed in several cell types 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164419 15453089 221234 17610 9605 PTGS2 COX-2 COX-2 7 4.4 Since its discovery in the early 1990s COX-2 has emerged as a major player in inflammatory reactions in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164420 15453089 221235 17610 9605 PTGS2 COX-2 COX-2 2 4.4 By extension COX-2 expression in brain has been associated with pro-inflammatory activities thought 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164421 15453089 221237 17610 9605 PTGS2 COX-2 COX-2 6 4.4 First in the central nervous system COX-2 is expressed under normal conditions and contributes to fundamental brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164422 15453089 221239 17610 9605 PTGS2 COX-2 COX-2 17 4.4 the last decade the evidence of a direct role of COX-2 in neurodegenerative events is still controversial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164423 15453089 221241 17610 9605 PTGS2 COX-2 COX-2 5 4.4 Furthermore the emerging role of COX-2 in behavioral and cognitive functions will be discussed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164424 15453089 221242 17610 9605 PTGS2 COX COX 1 0.6 Cyclooxygenase (COX), COX also known as prostaglandin (PG) PG H synthase catalyses the 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164425 15453089 221243 17610 9605 PTGS2 COX COX 0 0.6 COX has become a very popular enzyme since 1971 when it 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164426 15453089 221243 17610 9605 PTGS2 COX COX 26 0.6 (NSAIDs) NSAIDs exert their anti-inflammatory properties through the inhibition of COX enzymatic activity thus preventing PG synthesis ( 1 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164427 15453089 221244 17610 9605 PTGS2 COX COX 16 0.6 class of drugs affects many other important cellular targets nonetheless COX remains central to the development of anti-inflammatory treatments of a 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164428 15453089 221245 17610 9605 PTGS2 COX COX 0 0.6 COX is a unique enzyme 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164429 15453089 221247 17610 9605 PTGS2 COX COX 17 0.6 production of free radicals which are in part utilized by COX itself ( Fig 1 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164430 15453089 221248 17610 9605 PTGS2 COX COX 11 0.6 two enzymatic activities occur at distinct interacting sites on the COX molecule and external factors can affect each of them independently 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164431 15453089 221249 17610 9605 PTGS2 COX COX 5 0.6 Second during the cyclooxygenase activity COX undergoes a conformational rearrangement leading to an unstable intermediate which 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164432 15453089 221251 17610 9605 PTGS2 COX COX 0 0.6 COX is an integral membrane glycoprotein consisting of a homodimer with 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164433 15453089 221252 17609 9604 PTGS1 COX-1 COX-1 4 2.3 Besides a constitutive isoform (COX-1), COX-1 which is widely distributed in virtually all cell types and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164434 15453089 221252 17610 9605 PTGS2 COX-2 COX-2 27 4.4 to mediate physiological responses a second and inducible isoform termed COX-2 was identified in the early 1990s ( 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164435 15453089 221253 17610 9605 PTGS2 COX-2 COX-2 0 4.4 COX-2 is rapidly expressed in several cell types in response to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164436 15453089 221254 17609 9604 PTGS1 COX-1 COX-1 0 2.3 COX-1 and COX-2 are coded by 2 distinct genes located on 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164437 15453089 221254 17610 9605 PTGS2 COX-2 COX-2 0 4.4 COX-1 and COX-2 are coded by 2 distinct genes located on 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164438 15453089 221254 17610 9605 PTGS2 COX-2 COX-2 2 4.4 COX-1 and COX-2 are coded by 2 distinct genes located on human chromosome 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164439 15453089 221255 17610 9605 PTGS2 COX-2 COX-2 1 4.4 The COX-2 gene is characterized by the presence of a TATA box 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164440 15453089 221255 17610 9605 PTGS2 COX-2 COX-2 32 4.4 its promoter region which account for the complex regulation of COX-2 expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164441 15453089 221256 17610 9605 PTGS2 COX-2 COX-2 28 4.4 determinant or as translation inhibitory element suggesting post-transcriptional control of COX-2 expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164442 15453089 221257 17609 9604 PTGS1 COX-1 COX-1 4 2.3 On the contrary the COX-1 gene represents a classical _amp_#147 housekeeping_amp_#148 gene lacking of a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164443 15453089 221259 17609 9604 PTGS1 COX-1 COX-1 31 2.3 2 isoenzymes which could account for the different sensitivities of COX-1 and COX-2 to specific inhibitors ( 5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164444 15453089 221259 17610 9605 PTGS2 COX-2 COX-2 31 4.4 2 isoenzymes which could account for the different sensitivities of COX-1 and COX-2 to specific inhibitors ( 5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164445 15453089 221259 17610 9605 PTGS2 COX-2 COX-2 33 4.4 which could account for the different sensitivities of COX-1 and COX-2 to specific inhibitors ( 5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164446 15453089 221260 17610 9605 PTGS2 COX-2 COX-2 14 4.4 the 2 isoforms is the 18-amino acid insert near the COX-2 C-terminus which is not present in COX-1 and has allowed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164447 15453089 221260 17609 9604 PTGS1 COX-1 COX-1 21 2.3 insert near the COX-2 C-terminus which is not present in COX-1 and has allowed the production of specific antibodies 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164448 15453089 221261 17610 9605 PTGS2 COX COX 5 0.6 The distribution of the 2 COX isoforms has been extensively studied in rat and human tissues 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164449 15453089 221262 17609 9604 PTGS1 COX-1 COX-1 6 2.3 In the majority of the tissues COX-1 appears to be the only isoform constitutively expressed confirming the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164450 15453089 221263 17609 9604 PTGS1 COX-1 COX-1 10 2.3 However in brain testes and kidney macula densa cells both COX-1 and COX-2 are expressed under physiological conditions ( 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164451 15453089 221263 17610 9605 PTGS2 COX-2 COX-2 10 4.4 However in brain testes and kidney macula densa cells both COX-1 and COX-2 are expressed under physiological conditions ( 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164452 15453089 221263 17610 9605 PTGS2 COX-2 COX-2 12 4.4 brain testes and kidney macula densa cells both COX-1 and COX-2 are expressed under physiological conditions ( 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164453 15453089 221264 17609 9604 PTGS1 COX-1 COX-1 3 2.3 In rat brain COX-1 and COX-2 immunoreactivities are present in discrete neuronal populations distributed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164454 15453089 221264 17610 9605 PTGS2 COX-2 COX-2 3 4.4 In rat brain COX-1 and COX-2 immunoreactivities are present in discrete neuronal populations distributed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164455 15453089 221264 17610 9605 PTGS2 COX-2 COX-2 5 4.4 In rat brain COX-1 and COX-2 immunoreactivities are present in discrete neuronal populations distributed in distinct 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164456 15453089 221265 17609 9604 PTGS1 COX-1 COX-1 9 2.3 In other regions such as midbrain pons and medulla COX-1 immunoreactivity prevails ( 6 7 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164457 15453089 221266 17609 9604 PTGS1 COX-1 COX-1 4 2.3 Similarly mRNAs for both COX-1 and COX-2 are present in several regions of human brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164458 15453089 221266 17610 9605 PTGS2 COX-2 COX-2 4 4.4 Similarly mRNAs for both COX-1 and COX-2 are present in several regions of human brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164459 15453089 221266 17610 9605 PTGS2 COX-2 COX-2 6 4.4 Similarly mRNAs for both COX-1 and COX-2 are present in several regions of human brain although COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164460 15453089 221266 17610 9605 PTGS2 COX-2 COX-2 16 4.4 COX-2 are present in several regions of human brain although COX-2 is the prominent isoform particularly in the hippocampus ( 8 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164461 15453089 221267 17609 9604 PTGS1 COX-1 COX-1 4 2.3 The relative contribution of COX-1 and COX-2 activity to brain pathology and physiology has been 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164462 15453089 221267 17610 9605 PTGS2 COX-2 COX-2 4 4.4 The relative contribution of COX-1 and COX-2 activity to brain pathology and physiology has been 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164463 15453089 221267 17610 9605 PTGS2 COX-2 COX-2 6 4.4 The relative contribution of COX-1 and COX-2 activity to brain pathology and physiology has been recently questioned 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164464 15453089 221268 17609 9604 PTGS1 COX-1 COX-1 8 2.3 On one side it has been argued that COX-1 activity in brain diseases has been overlooked on the other 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164465 15453089 221268 17610 9605 PTGS2 COX-2 COX-2 24 4.4 been overlooked on the other side mandatory evidence suggests that COX-2 plays a special role in normal neuronal function and in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164466 15453089 221269 17609 9604 PTGS1 COX-1 COX-1 22 2.3 studies it is clear that the popular paradigm by which COX-1 serves physiological functions and COX-2 is responsible for _amp_#147 pathological_amp_#148 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164467 15453089 221269 17610 9605 PTGS2 COX-2 COX-2 27 4.4 the popular paradigm by which COX-1 serves physiological functions and COX-2 is responsible for _amp_#147 pathological_amp_#148 PGs cannot explain an increasing 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164468 15453089 221270 17610 9605 PTGS2 COX COX 5 0.6 Recently a third variant of COX named COX-3 and 2 partial COX-1 proteins (PCOX-1 PCOX-1 proteins 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164469 15453089 221270 17609 9604 PTGS1 COX3 COX-3 7 0.3 Recently a third variant of COX named COX-3 and 2 partial COX-1 proteins (PCOX-1 PCOX-1 proteins have been 11 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.00113354759003357<>ScoreDetail__7422|MT-CO3|0.000275008354684193__9604|PTGS1|0.00113354759003357__ 0 0 0 0 0 164470 15453089 221270 17610 9605 PTGS2 COX2 COX2 7 1.8 Recently a third variant of COX named COX-3 and 2 partial COX-1 proteins (PCOX-1 PCOX-1 proteins have been 15 JUMiner_v2.2 1 0 0 2 9605 TotalCon:2<>7421|MT-CO2|4513|Complete__9605|PTGS2|5743|Complete__<>AvaiableGeneRif=2<>BEST:9605|PTGS2|0.00189208129877986<>ScoreDetail__7421|MT-CO2|0.00113442571310638__9605|PTGS2|0.00189208129877986__ 0 0 0 0 0 164471 15453089 221270 17609 9604 PTGS1 COX-1 COX-1 11 2.3 a third variant of COX named COX-3 and 2 partial COX-1 proteins (PCOX-1 PCOX-1 proteins have been identified from canine and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164472 15453089 221270 17609 9604 PTGS1 PCOX1 PCOX-1 13 0.8 of COX named COX-3 and 2 partial COX-1 proteins (PCOX-1 PCOX-1 proteins have been identified from canine and human cerebral cortex 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164473 15453089 221271 17609 9604 PTGS1 COX3 COX-3 0 0.3 COX-3 and one of the PCOX-1 are products of the COX-1 11 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.00113354759003357<>ScoreDetail__7422|MT-CO3|0.000275008354684193__9604|PTGS1|0.00113354759003357__ 0 0 0 0 0 164474 15453089 221271 17609 9604 PTGS1 PCOX1 PCOX-1 5 0.8 COX-3 and one of the PCOX-1 are products of the COX-1 gene but retain intron 1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164475 15453089 221271 17609 9604 PTGS1 COX-1 COX-1 10 2.3 COX-3 and one of the PCOX-1 are products of the COX-1 gene but retain intron 1 in their mRNA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164476 15453089 221273 17609 9604 PTGS1 COX-1 COX-1 17 2.3 in the in cerebral cortex where the expression of the COX-1 variant gene accounts for ~5_amp_#37 of COX-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164477 15453089 221273 17609 9604 PTGS1 COX-1 COX-1 24 2.3 expression of the COX-1 variant gene accounts for ~5_amp_#37 of COX-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164478 15453089 221274 17609 9604 PTGS1 COX-1 COX-1 3 2.3 As its counterpart COX-1 COX-3 is not induced by acute inflammatory stimulation ( 13 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164479 15453089 221274 17609 9604 PTGS1 COX3 COX-3 4 0.3 As its counterpart COX-1 COX-3 is not induced by acute inflammatory stimulation ( 13 11 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.00113354759003357<>ScoreDetail__7422|MT-CO3|0.000275008354684193__9604|PTGS1|0.00113354759003357__ 0 0 0 0 0 164480 15453089 221275 17609 9604 PTGS1 COX3 COX-3 0 0.3 COX-3 but not PCOX-1 exhibits enzymatic activity that is glycosylation-dependent and 11 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.00113354759003357<>ScoreDetail__7422|MT-CO3|0.000275008354684193__9604|PTGS1|0.00113354759003357__ 0 0 0 0 0 164481 15453089 221275 17609 9604 PTGS1 PCOX1 PCOX-1 3 0.8 COX-3 but not PCOX-1 exhibits enzymatic activity that is glycosylation-dependent and especially sensitive to 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164482 15453089 221276 17609 9604 PTGS1 COX3 COX-3 1 0.3 Thus COX-3 could represent the brain-specific COX isoform the existence of which 11 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.00113354759003357<>ScoreDetail__7422|MT-CO3|0.000275008354684193__9604|PTGS1|0.00113354759003357__ 0 0 0 0 0 164483 15453089 221276 17610 9605 PTGS2 COX COX 6 0.6 Thus COX-3 could represent the brain-specific COX isoform the existence of which was hypothesized a few decades 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164484 15453089 221276 17610 9605 PTGS2 COX COX 36 0.6 of paracetamol in spite of its poor ability to inhibit COX from peripheral tissues ( 12 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164485 15453089 221277 17609 9604 PTGS1 COX3 COX-3 5 0.3 Nonetheless the functional role of COX-3 is largely unknown and more intense research is required to 11 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.00113354759003357<>ScoreDetail__7422|MT-CO3|0.000275008354684193__9604|PTGS1|0.00113354759003357__ 0 0 0 0 0 164486 15453089 221277 17609 9604 PTGS1 COX3 COX-3 20 0.3 more intense research is required to elucidate the contribution of COX-3 to the overall PG production in brain 11 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.00113354759003357<>ScoreDetail__7422|MT-CO3|0.000275008354684193__9604|PTGS1|0.00113354759003357__ 0 0 0 0 0 164487 15453089 221278 17610 9605 PTGS2 COX COX 4 0.6 The potential role of COX isoforms and PGs in brain diseases has been extensively reviewed 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164488 15453089 221279 17610 9605 PTGS2 COX-2 COX-2 2 4.4 Over-expression of COX-2 has been associated with neurotoxicity in acute conditions such as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164489 15453089 221280 17610 9605 PTGS2 COX-2 COX-2 8 4.4 However the beneficial or detrimental role played by COX-2 in inflammatory and neurodegenerative brain pathologies is still controversial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164490 15453089 221281 20996 11179 SOD1 ALS ALS 25 3.4 such as multiple sclerosis (MS), MS amyotrophic lateral sclerosis (ALS), ALS Parkinson disease (PD), PD Creutzfeldt-Jakob disease (CJD), CJD and Alzheimer 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164491 15453089 221281 17345 9449 PRNP CJD CJD 31 1.7 sclerosis (ALS), ALS Parkinson disease (PD), PD Creutzfeldt-Jakob disease (CJD), CJD and Alzheimer disease (AD) AD 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164492 15453089 221282 17610 9605 PTGS2 COX-2 COX-2 5 4.4 First the emerging role of COX-2 in cognitive functions will be discussed since understanding the role 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164493 15453089 221282 17610 9605 PTGS2 COX-2 COX-2 17 4.4 cognitive functions will be discussed since understanding the role of COX-2 in brain function is an important prerequisite to fully understanding 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164494 15453089 221282 17610 9605 PTGS2 COX-2 COX-2 35 4.4 to fully understanding how to exploit the potential benefits of COX-2 inhibition in disabling neurological diseases 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164495 15453089 221283 17610 9605 PTGS2 COX-2 COX-2 3 4.4 In mammalian brain COX-2 is constitutively expressed in specific neuronal populations under normal physiological 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164496 15453089 221284 17610 9605 PTGS2 COX-2 COX-2 3 4.4 In rat brain COX-2 mRNA and immunoreactivity were detected in dentate gyrus granule cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164497 15453089 221285 17610 9605 PTGS2 COX-2 COX-2 3 4.4 This _amp_#147 constitutive_amp_#148 neuronal COX-2 expression should be more correctly regarded as _amp_#147 dynamically_amp_#148 regulated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164498 15453089 221286 17610 9605 PTGS2 COX-2 COX-2 3 4.4 The dependence of COX-2 expression on natural excitatory synaptic activity is supported by the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164499 15453089 221286 17610 9605 PTGS2 COX-2 COX-2 16 4.4 natural excitatory synaptic activity is supported by the presence of COX-2 immunoreactivity in distal dendrites and dendritic spines which are involved 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164500 15453089 221287 17610 9605 PTGS2 COX-2 COX-2 13 4.4 distribution within a neuronal population is compatible with induction of COX-2 in subsets of neurons in response to natural excitatory synaptic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164501 15453089 221288 17610 9605 PTGS2 COX-2 COX-2 3 4.4 The involvement of COX-2 in synaptic activity is further supported by the developmental profile 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164502 15453089 221288 17610 9605 PTGS2 COX-2 COX-2 15 4.4 synaptic activity is further supported by the developmental profile of COX-2 expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164503 15453089 221289 17610 9605 PTGS2 COX-2 COX-2 3 4.4 In rat brain COX-2 expression follows developmental gradients and coincides with the critical period 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164504 15453089 221290 17610 9605 PTGS2 COX-2 COX-2 23 4.4 and abnormalities of dendritic branching_amp_#151 the laminar pattern of cortical COX-2 immunoreactivity is disrupted in that COX-2-positive neurons are decreased in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164505 15453089 221290 17610 9605 PTGS2 COX COX-2-positive 29 0.0 laminar pattern of cortical COX-2 immunoreactivity is disrupted in that COX-2-positive neurons are decreased in number and randomly distributed ( 18 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164506 15453089 221291 17610 9605 PTGS2 COX-2 COX-2 19 4.4 neurons during the first post-natal week showed decreased levels of COX-2 but not COX-1 in the hippocampus at adulthood 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164507 15453089 221291 17609 9604 PTGS1 COX-1 COX-1 22 2.3 first post-natal week showed decreased levels of COX-2 but not COX-1 in the hippocampus at adulthood 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164508 15453089 221292 17610 9605 PTGS2 COX-2 COX-2 24 4.4 of hippocampal cholinergic input may impact on the expression of COX-2 in hippocampal neurons and on the functional role of PGs 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164509 15453089 221293 17610 9605 PTGS2 COX-2 COX-2 3 4.4 Indirect evidence of COX-2 involvement in synaptic plasticity has been obtained in the recent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164510 15453089 221293 17610 9605 PTGS2 COX COX 17 0.6 plasticity has been obtained in the recent years by using COX inhibitors in in vivo and in vitro models of synaptic 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164511 15453089 221294 17610 9605 PTGS2 COX-2 COX-2 0 4.4 COX-2 inhibitors but not COX-1 selective inhibitors administered systemically shortly after 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164512 15453089 221294 17609 9604 PTGS1 COX-1 COX-1 4 2.3 COX-2 inhibitors but not COX-1 selective inhibitors administered systemically shortly after training in the Morris 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164513 15453089 221295 17610 9605 PTGS2 COX COX 4 0.6 Similarly intracerebral injection of COX inhibitors in chicks attenuated memory of a passive avoidance response 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164514 15453089 221296 17610 9605 PTGS2 COX-2 COX-2-specific 6 1.8 In addition pre-training infusion of a COX-2-specific inhibitor (celecoxib) celecoxib in the hippocampus of adult rats impaired 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164515 15453089 221296 17610 9605 PTGS2 COX-2 COX-2 26 4.4 acquisition of the Morris water maze suggesting that in rats COX-2 activity in the hippocampus is necessary for both memory and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164516 15453089 221297 17610 9605 PTGS2 COX COX 11 0.6 keeping with these findings systemic administration of ibuprofen a non-selective COX inhibitor caused deficits in spatial learning in the water maze 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164517 15453089 221299 1624 1033 BDNF BDNF BDNF 14 0.3 the increase in PGE 2 and brain-derived growth factor (BDNF) BDNF levels following LTP and spatial learning 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164518 15453089 221300 1624 1033 BDNF BDNF BDNF 26 0.3 LTP and spatial learning most likely through an increase in BDNF levels supporting the hypothesis that COX activity plays a permissive 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164519 15453089 221300 17610 9605 PTGS2 COX COX 32 0.6 through an increase in BDNF levels supporting the hypothesis that COX activity plays a permissive role in synaptic plasticity and spatial 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164520 15453089 221300 1624 1033 BDNF BDNF BDNF-associated 45 0.3 a permissive role in synaptic plasticity and spatial learning via BDNF-associated mechanisms ( 23 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164521 15453089 221301 16457 8891 PGD PGD PGD 9 0.0 In agreement with this hypothesis PGE 2 but not PGD 2 reversed the suppression of LTP induced by COX-2-inhibitor in 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 164522 15453089 221301 17610 9605 PTGS2 COX COX-2-inhibitor 19 0.0 not PGD 2 reversed the suppression of LTP induced by COX-2-inhibitor in hippocampal dentate granule neurons in vitro ( 24 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164523 15453089 221302 17610 9605 PTGS2 COX-2 COX-2 12 4.4 2 which is preferentially formed during the enzymatic activity of COX-2 rather than of COX-1 could participate to synaptic plasticity through 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164524 15453089 221302 17609 9604 PTGS1 COX-1 COX-1 16 2.3 formed during the enzymatic activity of COX-2 rather than of COX-1 could participate to synaptic plasticity through several mechanisms including modulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164525 15453089 221303 17610 9605 PTGS2 COX-2 COX-2 34 4.4 neocortical blood flow in response to vibrissal stimulation by the COX-2 inhibitor NS398 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164526 15453089 221303 17610 9605 PTGS2 COX COX-2-derived 1 0.0 Moreover COX-2-derived PGs are involved in the coupling of synaptic plasticity with 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164527 15453089 221304 17610 9605 PTGS2 COX-2 COX-2 11 4.4 hyperemic response was also impaired in mutant mice lacking of COX-2 ( 26 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164528 15453089 221305 17610 9605 PTGS2 COX-2 COX-2 11 4.4 spite of the emerging evidence of a physiological role for COX-2 in brain development and function COX-2 knockout mice show no 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164529 15453089 221305 17610 9605 PTGS2 COX-2 COX-2 17 4.4 a physiological role for COX-2 in brain development and function COX-2 knockout mice show no gross abnormalities of brain anatomy 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164530 15453089 221307 17609 9604 PTGS1 COX-1 COX-1 6 2.3 In addition significant compensatory effects of COX-1 and possibly COX-3 cannot be ruled out 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164531 15453089 221307 17609 9604 PTGS1 COX3 COX-3 9 0.3 In addition significant compensatory effects of COX-1 and possibly COX-3 cannot be ruled out 11 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.00113354759003357<>ScoreDetail__7422|MT-CO3|0.000275008354684193__9604|PTGS1|0.00113354759003357__ 0 0 0 0 0 164532 15453089 221313 17610 9605 PTGS2 COX-2 COX-2 6 4.4 In this light the expression of COX-2 and its contribution to the pathogenic events in MS have 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164533 15453089 221314 17610 9605 PTGS2 COX-2 COX-2 0 4.4 COX-2 immunoreactivity has been found in experimental autoimmune encephalomyelitis (EAE), EAE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164534 15453089 221315 17610 9605 PTGS2 COX-2 COX-2 25 4.4 proteolipid protein revealed that during the acute phase of EAE COX-2 expression is confined within infiltrating macrophages and ramified microglia close 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164535 15453089 221316 17610 9605 PTGS2 COX-2 COX-2 5 4.4 Very rare reactive astrocytes expressed COX-2 in this phase but their number significantly increased during relapse 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164536 15453089 221316 17610 9605 PTGS2 COX-2 COX-2 19 4.4 but their number significantly increased during relapse phase suggesting that COX-2 induction in astrocytes could be due to soluble factors i.e 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164537 15453089 221317 17610 9605 PTGS2 COX-2 COX-2 22 4.4 a peptide of another myelin protein the myelin basic protein COX-2 immunoreactivity was exclusively found associated with neurons and endothelial cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164538 15453089 221318 17610 9605 PTGS2 COX COX-2-positive 3 0.0 The number of COX-2-positive endothelial cells increased with the progression of the disease most 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164539 15453089 221319 17609 9604 PTGS1 COX-1 COX-1 4 2.3 Macrophage/ Macrophage microglia-like cells expressing COX-1 were disseminated throughout the brain parenchyma of control animals 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164540 15453089 221320 17609 9604 PTGS1 COX COX-1-positive 5 0.0 In EAE the number of COX-1-positive macrophages increased along with that of COX-2-positive cells 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164541 15453089 221320 17610 9605 PTGS2 COX COX-2-positive 12 0.0 the number of COX-1-positive macrophages increased along with that of COX-2-positive cells 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164542 15453089 221321 17610 9605 PTGS2 COX-2 COX-2 31 4.4 brain parenchyma breakdown of BBB primary demyelination and axon damage COX-2 expression was restricted to major infiltrating hematogenous cell populations such 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164543 15453089 221322 17610 9605 PTGS2 COX-2 COX-2 16 4.4 macrophages but the possibility that some endothelial cells also expressed COX-2 could not be ruled out 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164544 15453089 221323 17610 9605 PTGS2 COX-2 COX-2 1 4.4 Neuronal COX-2 was not affected by the ongoing inflammation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164545 15453089 221324 17610 9605 PTGS2 COX-2 COX-2 22 4.4 broad area surrounding the inflammatory lesions there was no obvious COX-2 staining in these cells indicating that the upregulation of COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164546 15453089 221324 17610 9605 PTGS2 COX-2 COX-2 32 4.4 COX-2 staining in these cells indicating that the upregulation of COX-2 expression in this model of chronic immune-mediated lesions is remarkably 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164547 15453089 221325 17610 9605 PTGS2 COX-2 COX-2 3 4.4 A similar restricted COX-2 expression has been described in brain tissues from 7 MS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164548 15453089 221326 17610 9605 PTGS2 COX-2 COX-2 11 4.4 these specimens characterized by the presence of chronic active lesions COX-2 expression was studied by sophisticated confocal microscopy analysis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164549 15453089 221327 17610 9605 PTGS2 COX COX-2-positive 0 0.0 COX-2-positive cells were present in all chronic active lesions examined and 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164550 15453089 221328 17610 9605 PTGS2 COX-2 COX-2 0 4.4 COX-2 immunoreactivity was largely but not exclusively associated with cells expressing 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164551 15453089 221328 7438 3613 FCGR1A CD64 CD64 14 1.0 exclusively associated with cells expressing the macrophage/microglial macrophage microglial marker CD64 the FC receptor typically associated with activated macrophages 1 JUMiner_v2.2 1 0 0 2 3613 TotalCon:3<>3613|FCGR1A|2209|Complete__3614|FCGR1B|2210|Complete__3615|FCGR1C|2211|No_GeneRif__<>AvaiableGeneRif=2<>BEST:3613|FCGR1A|0.000638172481034299<>ScoreDetail__3614|FCGR1B|0.000511948995102179__3613|FCGR1A|0.000638172481034299__ 0 0 0 0 0 164552 15453089 221329 7438 3613 FCGR1A CD64 CD64-positive 3 1.0 However not all CD64-positive cells expressed COX-2 1 JUMiner_v2.2 1 2 32 0 2 3613 TotalCon:3<>3613|FCGR1A|2209|Complete__3614|FCGR1B|2210|Complete__3615|FCGR1C|2211|No_GeneRif__<>AvaiableGeneRif=2<>BEST:3613|FCGR1A|0.000638172481034299<>ScoreDetail__3614|FCGR1B|0.000511948995102179__3613|FCGR1A|0.000638172481034299__ 0 0 0 0 0 164553 15453089 221329 17610 9605 PTGS2 COX-2 COX-2 6 4.4 However not all CD64-positive cells expressed COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164554 15453089 221330 17610 9605 PTGS2 COX-2 COX-2 2 4.4 Expression of COX-2 was frequently associated with that of inducible NO synthase (iNOS), 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164555 15453089 221330 14535 7873 NOS2A iNOS iNOS 12 1.0 was frequently associated with that of inducible NO synthase (iNOS), iNOS suggesting that both enzymes could contribute to the progression of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164556 15453089 221331 17610 9605 PTGS2 COX-2 COX-2 8 4.4 The authors also propose that the colocalization of COX-2 and iNOS may be functionally linked to oligodendroglial excitotoxic death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164557 15453089 221331 14535 7873 NOS2A iNOS iNOS 10 1.0 The authors also propose that the colocalization of COX-2 and iNOS may be functionally linked to oligodendroglial excitotoxic death in MS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164558 15453089 221332 17610 9605 PTGS2 COX-2 COX-2 5 4.4 Nonetheless a protective role of COX-2 in MS cannot be excluded 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164559 15453089 221336 17610 9605 PTGS2 COX COX-derived 16 0.0 co-administration of misoprostol a PGE 2 analog suggesting that distinct COX-derived products (i.e i.e ROS and PGs may have protective or 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164560 15453089 221336 18723 10261 ROS1 ROS ROS 19 0.0 PGE 2 analog suggesting that distinct COX-derived products (i.e i.e ROS and PGs may have protective or detrimental effects in EAE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164561 15453089 221338 11629 6493 LAMC2 CSF CSF 3 0.3 Recently cerebrospinal fluid (CSF) CSF levels of PGE 2 and isoprostane 8-epi-PGF 2 a stable 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164562 15453089 221341 11629 6493 LAMC2 CSF CSF 12 0.3 of PGE 2 and that of 8-epi-PGF 2 in the CSF of each single subject were not correlated suggesting that PG 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164563 15453089 221343 20996 11179 SOD1 ALS ALS 3 3.4 Amyotrophic lateral sclerosis (ALS) ALS is a devastating neurodegenerative disease characterized by the progressive loss 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164564 15453089 221345 20996 11179 SOD1 SOD1 SOD1 11 3.4 gene encoding for the Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 account for a familial form of ALS linked to chromosome 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164565 15453089 221345 20996 11179 SOD1 ALS ALS 18 3.4 superoxide dismutase (SOD1) SOD1 account for a familial form of ALS linked to chromosome 21q 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164566 15453089 221346 20996 11179 SOD1 SOD1 SOD1 12 3.4 has led to the development of transgenic mice expressing mutant SOD1 with phenotype that mimics clinical and pathological characteristics of the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164567 15453089 221347 20996 11179 SOD1 ALS ALS 8 3.4 Spinal cord tissue from patients who died of ALS shows several neuroinflammatory changes that are found in other neurodegenerative 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164568 15453089 221349 11629 6493 LAMC2 CSF CSF 3 0.3 In addition high CSF levels of glutamate and excitotoxicity have been reported in ALS 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164569 15453089 221349 20996 11179 SOD1 ALS ALS 13 3.4 CSF levels of glutamate and excitotoxicity have been reported in ALS ( 41 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164570 15453089 221350 17610 9605 PTGS2 COX-2 COX-2 4 4.4 The well-established role of COX-2 in inflammation and in glutamate-dependent neurotoxicity has set the basis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164571 15453089 221350 17610 9605 PTGS2 COX-2 COX-2 19 4.4 glutamate-dependent neurotoxicity has set the basis for the hypothesis of COX-2 involvement in ALS pathogenesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164572 15453089 221350 20996 11179 SOD1 ALS ALS 22 3.4 set the basis for the hypothesis of COX-2 involvement in ALS pathogenesis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164573 15453089 221351 17610 9605 PTGS2 COX-2 COX-2 0 4.4 COX-2 mRNA and protein were increased in postmortem spinal cords of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164574 15453089 221351 20996 11179 SOD1 ALS ALS 11 3.4 mRNA and protein were increased in postmortem spinal cords of ALS patients ( 42 and transgenic mutated SOD1 mice ( 43 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164575 15453089 221351 20996 11179 SOD1 SOD1 SOD1 19 3.4 spinal cords of ALS patients ( 42 and transgenic mutated SOD1 mice ( 43 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164576 15453089 221352 17610 9605 PTGS2 COX-2 COX-2 11 4.4 of PGE 2 tissue levels paralleled the increased expression of COX-2 ( 43 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164577 15453089 221353 11629 6493 LAMC2 CSF CSF 12 0.3 independent studies reported increased levels of PGE 2 in the CSF of ALS patients ( 44 45 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164578 15453089 221353 20996 11179 SOD1 ALS ALS 14 3.4 reported increased levels of PGE 2 in the CSF of ALS patients ( 44 45 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164579 15453089 221354 17610 9605 PTGS2 COX-2 COX-2 4 4.4 The cell types expressing COX-2 have been identified in both animal and human specimens 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164580 15453089 221355 17610 9605 PTGS2 COX-2 COX-2 3 4.4 Under normal conditions COX-2 is expressed in neurons in the spinal cord dorsal and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164581 15453089 221356 20996 11179 SOD1 ALS ALS 5 3.4 In postmortem spinal cord of ALS patients COX-2 expression was markedly increased and localized to both 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164582 15453089 221356 17610 9605 PTGS2 COX-2 COX-2 7 4.4 In postmortem spinal cord of ALS patients COX-2 expression was markedly increased and localized to both neurons and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164583 15453089 221357 17610 9605 PTGS2 COX COX-2-positive 3 0.0 The number of COX-2-positive motor neurons and interneurons was significantly increased in spite of 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164584 15453089 221358 17610 9605 PTGS2 COX-2 COX-2 2 4.4 In addition COX-2 was associated with astrocytes and and to a much lesser 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164585 15453089 221359 17609 9604 PTGS1 COX-1 COX-1 2 2.3 In contrast COX-1 immunoreactivity was confined to some microglial cells and there was 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164586 15453089 221359 20996 11179 SOD1 ALS ALS 21 3.4 there was no significant difference was detected between control and ALS specimens ( 45 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164587 15453089 221360 17610 9605 PTGS2 COX-2 COX-2 4 4.4 A similar pattern of COX-2 expression was reported for the mutated SOD1 transgenic mice ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164588 15453089 221360 20996 11179 SOD1 SOD1 SOD1 11 3.4 similar pattern of COX-2 expression was reported for the mutated SOD1 transgenic mice ( 43 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164589 15453089 221361 17610 9605 PTGS2 COX-2 COX-2 3 4.4 The role of COX-2 activity in ALS was examined by using selective COX-2 inhibitors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164590 15453089 221361 20996 11179 SOD1 ALS ALS 6 3.4 The role of COX-2 activity in ALS was examined by using selective COX-2 inhibitors 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164591 15453089 221361 17610 9605 PTGS2 COX-2 COX-2 12 4.4 of COX-2 activity in ALS was examined by using selective COX-2 inhibitors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164592 15453089 221362 17610 9605 PTGS2 COX-2 COX-2 5 4.4 In the first study the COX-2 inhibitor SC236 significantly protected motor neurons in an organotypic spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164593 15453089 221363 17610 9605 PTGS2 COX-2 COX-2 4 4.4 These findings suggested that COX-2 could take part in the excitotoxic damage caused by elevated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164594 15453089 221364 20996 11179 SOD1 SOD1 SOD1 8 3.4 Subsequently the same group showed that treatment of SOD1 transgenic mice with COX-2 inhibitor celecoxib significantly delayed the onset 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164595 15453089 221364 17610 9605 PTGS2 COX-2 COX-2 12 4.4 same group showed that treatment of SOD1 transgenic mice with COX-2 inhibitor celecoxib significantly delayed the onset of disease prolonged the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164596 15453089 221365 17610 9605 PTGS2 COX-2 COX-2 6 4.4 These studies suggest that inhibition of COX-2 could have therapeutic benefits by altering the cascade of events 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164597 15453089 221365 20996 11179 SOD1 ALS ALS 24 3.4 cascade of events leading to the progressive neuronal death in ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164598 15453089 221366 17610 9605 PTGS2 COX-2 COX-2 7 4.4 However in these studies mice received the COX-2 inhibitor treatment beginning several weeks before the onset of disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164599 15453089 221367 17610 9605 PTGS2 COX-2 COX-2 4 4.4 Thus the efficacy of COX-2 inhibition in the presence of overt clinical signs of disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164600 15453089 221368 17610 9605 PTGS2 COX-2 COX-2 6 4.4 Several mechanisms could be triggered by COX-2 overexpression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164601 15453089 221369 17610 9605 PTGS2 COX-2 COX-2 12 4.4 to the enhancing effect of PGE 2 on glutamate release COX-2 could contribute to oxidative stress-mediated damage by producing oxidizing reactive 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164602 15453089 221370 20996 11179 SOD1 SOD1 SOD1 3 3.4 In transgenic mutated SOD1 mice COX-2 and iNOS are induced with a similar temporal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164603 15453089 221370 17610 9605 PTGS2 COX-2 COX-2 5 4.4 In transgenic mutated SOD1 mice COX-2 and iNOS are induced with a similar temporal pattern and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164604 15453089 221370 14535 7873 NOS2A iNOS iNOS 7 1.0 In transgenic mutated SOD1 mice COX-2 and iNOS are induced with a similar temporal pattern and co-expression of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164605 15453089 221371 17610 9605 PTGS2 COX-2 COX-2 0 4.4 COX-2 could also contribute to ALS by promoting inflammatory processes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164606 15453089 221371 20996 11179 SOD1 ALS ALS 5 3.4 COX-2 could also contribute to ALS by promoting inflammatory processes 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164607 15453089 221373 24402 12856 YY1 DELTA DELTA 17 1.3 can be generated and influence the course of disease 15-deoxy- DELTA 12-14 -PGJ 2 (15d-PGJ 15d-PGJ 2 immunoreactivity was found in 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>9543|PSMB6|5694|No_GeneRif__12856|YY1|7528|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 164608 15453089 221373 20996 11179 SOD1 ALS ALS 32 3.4 15d-PGJ 2 immunoreactivity was found in spinal cords of sporadic ALS patients ( 48 15d-PGJ 2 derives from the non-enzymatic dehydration 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131390228980071<>ScoreDetail__5468|IGFALS|0.000611670676507768__11179|SOD1|0.00131390228980071__ 0 0 0 0 0 164609 15453089 221373 16457 8891 PGD PGD PGD 45 0.0 ( 48 15d-PGJ 2 derives from the non-enzymatic dehydration of PGD 2 a major brain PG and activates the nuclear receptor 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 164610 15453089 221384 17610 9605 PTGS2 COX COX 15 0.6 been related to free radical scavenging effects rather then to COX inhibition or attenuation of inflammation ( 51 52 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164611 15453089 221385 17610 9605 PTGS2 COX COX 7 0.6 Two studies have investigated the expression of COX isoforms in postmortem PD specimens or in PD experimental models 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164612 15453089 221386 17610 9605 PTGS2 COX-2 COX-2 8 4.4 The first study reported an increased expression of COX-2 in ameboid or activated microglial cells in the substantia nigra 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164613 15453089 221386 17610 9605 PTGS2 COX-2 COX-2 28 4.4 nigra from 11 idiopathic PD patients whereas neuronal and astroglial COX-2 expression was not different in the control and PD groups 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164614 15453089 221387 17609 9604 PTGS1 COX-1 COX-1 1 2.3 Moderate COX-1 immunoreactivity was observed in some neuronal somata and processes and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164615 15453089 221387 17610 9605 PTGS2 COX-2 COX-2 30 4.4 that the greater potential for PG synthesis is associated to COX-2 and microglial cells ( 53 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164616 15453089 221388 17610 9605 PTGS2 COX-2 COX-2 13 4.4 the second and more recent study ( 52 showed that COX-2 is specifically induced in substantia nigra dopaminergic neurons in postmortem 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164617 15453089 221391 17610 9605 PTGS2 COX-2 COX-2 3 4.4 The involvement of COX-2 in PD neurodegeneration was further suggested by the observation that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164618 15453089 221391 17610 9605 PTGS2 COX-2 COX-2 19 4.4 suggested by the observation that MPTP neurodegeneration was mitigated in COX-2 but not in COX-1 knock out mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164619 15453089 221391 17609 9604 PTGS1 COX-1 COX-1 23 2.3 that MPTP neurodegeneration was mitigated in COX-2 but not in COX-1 knock out mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164620 15453089 221394 17345 9449 PRNP CJD CJD 2 1.7 Creutzfeldt-Jakob disease (CJD) CJD is the best known human form of transmissible spongiform encephalopathies 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164621 15453089 221395 926 620 APP amyloid amyloid 8 1.0 The characteristic neuropathological signs of the disease are amyloid deposition of the proteinase-resistant prion protein (PrP PrP res or 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 164622 15453089 221395 2163 1325 C4BPA PrP PrP 15 1.3 disease are amyloid deposition of the proteinase-resistant prion protein (PrP PrP res or PrP Sc astrocytosis and spongiform degeneration 1 JUMiner_v2.2 1 0 0 2 9353 TotalCon:4<>9353|PRDX2|7001|Complete__9449|PRNP|5621|Complete__47|ABCB6|10058|Complete__1325|C4BPA|722|Complete__<>AvaiableGeneRif=4<>BEST:9353|PRDX2|0.00101795470066014<>ScoreDetail__1325|C4BPA|0.000479151084517577__47|ABCB6|0.000349949098312973__9353|PRDX2|0.00101795470066014__9449|PRNP|0.000586393185857164__ 0 0 0 0 0 164623 15453089 221395 2163 1325 C4BPA PrP PrP 18 1.3 deposition of the proteinase-resistant prion protein (PrP PrP res or PrP Sc astrocytosis and spongiform degeneration 1 JUMiner_v2.2 1 0 0 2 9353 TotalCon:4<>9353|PRDX2|7001|Complete__9449|PRNP|5621|Complete__47|ABCB6|10058|Complete__1325|C4BPA|722|Complete__<>AvaiableGeneRif=4<>BEST:9353|PRDX2|0.00101795470066014<>ScoreDetail__1325|C4BPA|0.000479151084517577__47|ABCB6|0.000349949098312973__9353|PRDX2|0.00101795470066014__9449|PRNP|0.000586393185857164__ 0 0 0 0 0 164624 15453089 221396 17345 9449 PRNP CJD CJD 11 1.7 further disease hallmark is the extensive microglial activation observed in CJD patients as well as in experimental prion diseases which supports 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164625 15453089 221397 10437 5992 IL1B IL-1 IL-1 12 1.0 of the prominent microglial activation classical pro-inflammatory mediators such as IL-1 IL-6 TNF- alpha and IFN- gamma were not detected in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164626 15453089 221397 10463 6018 IL6 IL-6 IL-6 13 1.0 the prominent microglial activation classical pro-inflammatory mediators such as IL-1 IL-6 TNF- alpha and IFN- gamma were not detected in significant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164627 15453089 221397 9905 5438 IFNG IFN IFN- 16 0.3 classical pro-inflammatory mediators such as IL-1 IL-6 TNF- alpha and IFN- gamma were not detected in significant amount in a murine 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000717129499255751<>ScoreDetail__5438|IFNG|0.000582168758438777__5417|IFNA1|0.000717129499255751__ 0 0 0 0 0 164628 15453089 221397 22551 11892 TNF TNF TNF- 14 0.4 prominent microglial activation classical pro-inflammatory mediators such as IL-1 IL-6 TNF- alpha and IFN- gamma were not detected in significant amount 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164629 15453089 221399 17610 9605 PTGS2 COX-2 COX-2 14 4.4 PGE 2 levels was associated with a strong induction of COX-2 expression which increased with the progression of disease and was 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164630 15453089 221400 17609 9604 PTGS1 COX COX-1-positive 2 0.0 Few scattered COX-1-positive microglia-like cells were found in control and infected brains ( 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164631 15453089 221401 17345 9449 PRNP CJD CJD 23 1.7 mice were infected with homogenates from 2 cases of genetic CJD and 3 cases of sporadic CJD ( 57 suggesting that 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164632 15453089 221401 17345 9449 PRNP CJD CJD 29 1.7 2 cases of genetic CJD and 3 cases of sporadic CJD ( 57 suggesting that the selective upregulation of COX-2 in 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164633 15453089 221401 17610 9605 PTGS2 COX-2 COX-2 39 4.4 sporadic CJD ( 57 suggesting that the selective upregulation of COX-2 in microglial cells is not characteristic of a specific prion 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164634 15453089 221402 17609 9604 PTGS1 COX-1 COX-1 11 2.3 results were reported in a recent study in which both COX-1 and COX-2 were increased in sporadic CJD cortex ( 58 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164635 15453089 221402 17610 9605 PTGS2 COX-2 COX-2 11 4.4 results were reported in a recent study in which both COX-1 and COX-2 were increased in sporadic CJD cortex ( 58 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164636 15453089 221402 17610 9605 PTGS2 COX-2 COX-2 13 4.4 reported in a recent study in which both COX-1 and COX-2 were increased in sporadic CJD cortex ( 58 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164637 15453089 221402 17345 9449 PRNP CJD CJD 18 1.7 in which both COX-1 and COX-2 were increased in sporadic CJD cortex ( 58 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164638 15453089 221403 17609 9604 PTGS1 COX-1 COX-1 0 2.3 COX-1 immunoreactivity was present in macrophages/microglial macrophages microglial cells whereas COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164639 15453089 221403 17610 9605 PTGS2 COX-2 COX-2 8 4.4 COX-1 immunoreactivity was present in macrophages/microglial macrophages microglial cells whereas COX-2 was predominantly in neurons mRNAs and proteins of both isoforms 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164640 15453089 221403 17345 9449 PRNP CJD CJD 28 1.7 isoforms were higher in tissue from temporal lobe of 1 CJD patient when compared to 1 neuropathologically unaltered control case 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164641 15453089 221404 17610 9605 PTGS2 COX COX 1 0.6 Increased COX activity in prion diseases was confirmed by 2 studies ( 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164642 15453089 221404 11629 6493 LAMC2 CSF CSF 17 0.3 was confirmed by 2 studies ( 55 59 reporting elevated CSF PGE 2 levels in a group of 62 subjects affected 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164643 15453089 221404 17345 9449 PRNP CJD CJD 32 1.7 a group of 62 subjects affected by sporadic and genetic CJD and in 18 cases of variant CJD the novel human 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164644 15453089 221404 17345 9449 PRNP CJD CJD 39 1.7 sporadic and genetic CJD and in 18 cases of variant CJD the novel human form associated with the consumption of contaminated 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164645 15453089 221405 17345 9449 PRNP CJD CJD 2 1.7 In sporadic CJD patients higher CSF levels of PGE 2 were associated with 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164646 15453089 221405 11629 6493 LAMC2 CSF CSF 5 0.3 In sporadic CJD patients higher CSF levels of PGE 2 were associated with shorter survival 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164647 15453089 221406 11629 6493 LAMC2 CSF CSF 10 0.3 PGE 2 levels were not dependent on the time of CSF sampling during the course of the disease suggesting that PGE 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164648 15453089 221407 11629 6493 LAMC2 CSF CSF 8 0.3 The increased levels of PGE 2 in the CSF of CJD patients and the high expression of COX-2 in 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164649 15453089 221407 17345 9449 PRNP CJD CJD 10 1.7 The increased levels of PGE 2 in the CSF of CJD patients and the high expression of COX-2 in microglial cells 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164650 15453089 221407 17610 9605 PTGS2 COX-2 COX-2 17 4.4 the CSF of CJD patients and the high expression of COX-2 in microglial cells in experimental prion diseases suggest that PGE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164651 15453089 221408 17345 9449 PRNP CJD CJD 1 1.7 In CJD abundance of apoptotic neurons correlated well with microglial activation ( 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164652 15453089 221408 17610 9605 PTGS2 COX-2 COX-2 29 4.4 cells with apoptotic neurons has been reported to selectively promote COX-2 expression and PGE 2 synthesis ( 61 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164653 15453089 221409 2163 1325 C4BPA PrP PrP 18 1.3 death as suggested by the observation that in neuroblastoma cells PrP peptides increase PGE 2 levels and COX-1 inhibitors protect against 1 JUMiner_v2.2 1 0 0 2 9353 TotalCon:4<>9353|PRDX2|7001|Complete__9449|PRNP|5621|Complete__47|ABCB6|10058|Complete__1325|C4BPA|722|Complete__<>AvaiableGeneRif=4<>BEST:9353|PRDX2|0.00101795470066014<>ScoreDetail__1325|C4BPA|0.000479151084517577__47|ABCB6|0.000349949098312973__9353|PRDX2|0.00101795470066014__9449|PRNP|0.000586393185857164__ 0 0 0 0 0 164654 15453089 221409 17609 9604 PTGS1 COX-1 COX-1 25 2.3 in neuroblastoma cells PrP peptides increase PGE 2 levels and COX-1 inhibitors protect against PrP toxicity ( 62 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164655 15453089 221409 2163 1325 C4BPA PrP PrP 29 1.3 peptides increase PGE 2 levels and COX-1 inhibitors protect against PrP toxicity ( 62 1 JUMiner_v2.2 1 0 0 2 9353 TotalCon:4<>9353|PRDX2|7001|Complete__9449|PRNP|5621|Complete__47|ABCB6|10058|Complete__1325|C4BPA|722|Complete__<>AvaiableGeneRif=4<>BEST:9353|PRDX2|0.00101795470066014<>ScoreDetail__1325|C4BPA|0.000479151084517577__47|ABCB6|0.000349949098312973__9353|PRDX2|0.00101795470066014__9449|PRNP|0.000586393185857164__ 0 0 0 0 0 164656 15453089 221410 17610 9605 PTGS2 COX COX 4 0.6 By contrast the non-selective COX inhibitor indomethacin had no significant effect on onset of clinical 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164657 15453089 221411 17345 9449 PRNP CJD CJD 10 1.7 At present whether PGE 2 contributes to neuronal death in CJD is a consequence of neuronal apoptosis or is just an 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 164658 15453089 221412 926 620 APP amyloid amyloid 20 1.0 in the elderly characterized by senile plaques neurofibrillary tangles and amyloid angiopathy 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 164659 15453089 221415 17610 9605 PTGS2 COX COX 7 0.6 The concept of a pathogenic role of COX in AD is deeply rooted in epidemiological studies reporting an 3 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 164660 15453089 221416 17609 9604 PTGS1 COX-1 COX-1 8 2.3 Over the last 10 years several analyses of COX-1 and COX-2 expressions have been carried out in animal models 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164661 15453089 221416 17610 9605 PTGS2 COX-2 COX-2 8 4.4 Over the last 10 years several analyses of COX-1 and COX-2 expressions have been carried out in animal models 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164662 15453089 221416 17610 9605 PTGS2 COX-2 COX-2 10 4.4 Over the last 10 years several analyses of COX-1 and COX-2 expressions have been carried out in animal models and postmortem 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164663 15453089 221416 17610 9605 PTGS2 COX-2 COX-2 38 4.4 still controversial body of evidence pointing to the involvement of COX-2 in the cascade of events leading to neurodegeneration in AD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164664 15453089 221417 17610 9605 PTGS2 COX-2 COX-2 0 4.4 COX-2 mRNA levels in AD brains were reported as either decreased 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164665 15453089 221417 17610 9605 PTGS2 COX-2 COX-2 25 4.4 9 65 66 possibly because of the short half-life of COX-2 transcripts or individual variability of inflammatory-related processes ( 67 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164666 15453089 221419 17610 9605 PTGS2 COX-2 COX-2 5 4.4 Several studies reported increased neuronal COX-2 immunoreactivity compared to control brain tissues ( 9 68 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164667 15453089 221420 17610 9605 PTGS2 COX-2 COX-2 6 4.4 However in other studies in which COX-2 expression was related to specific hallmarks of the disease such 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164668 15453089 221420 17610 9605 PTGS2 COX COX-2-positive 29 0.0 dementia rating and Braak stage of disease the number of COX-2-positive neurons decreased with the severity of dementia 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164669 15453089 221421 17610 9605 PTGS2 COX COX-2-positive 4 0.0 In end stage AD COX-2-positive neurons were significantly fewer than in non-demented controls ( 68 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164670 15453089 221422 17610 9605 PTGS2 COX-2 COX-2 13 4.4 more recent study ( 70 the number of neurons expressing COX-2 negatively correlated with the Braak score for amyloid deposits although 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164671 15453089 221422 926 620 APP amyloid amyloid 21 1.0 neurons expressing COX-2 negatively correlated with the Braak score for amyloid deposits although a moderate albeit non-significant COX-2 increase was found 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 164672 15453089 221422 17610 9605 PTGS2 COX-2 COX-2 28 4.4 Braak score for amyloid deposits although a moderate albeit non-significant COX-2 increase was found at Braak stage A corresponding to the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164673 15453089 221423 17610 9605 PTGS2 COX-2 COX-2 0 4.4 COX-2 immunoreactivity did not correlate with Braak staging for neurofibrillary changes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164674 15453089 221424 17610 9605 PTGS2 COX-2 COX-2 5 4.4 These recent studies suggest that COX-2 expression varies with the disease stage and this may explain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164675 15453089 221425 17610 9605 PTGS2 COX-2 COX-2 13 4.4 also reported a colocalization and a significant correlation of neuronal COX-2 expression with cell cycle regulators involved in controlling the G 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164676 15453089 221427 17610 9605 PTGS2 COX-2 COX-2 6 4.4 Although there are some indications that COX-2 might regulate cell cycle progression ( 70 the functional link 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164677 15453089 221427 17610 9605 PTGS2 COX-2 COX-2 19 4.4 regulate cell cycle progression ( 70 the functional link between COX-2 and cell cycle alteration remains elusive 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164678 15453089 221428 17610 9605 PTGS2 COX-2 COX-2 6 4.4 Nonetheless it can be suggested that COX-2 and cell cycle proteins are involved in early steps leading 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164679 15453089 221429 17610 9605 PTGS2 COX-2 COX-2 3 4.4 In contrast to COX-2 the levels of COX-1 mRNA and protein were not significantly 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164680 15453089 221429 17609 9604 PTGS1 COX-1 COX-1 7 2.3 In contrast to COX-2 the levels of COX-1 mRNA and protein were not significantly altered in AD brains 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164681 15453089 221430 17609 9604 PTGS1 COX-1 COX-1 0 2.3 COX-1 appeared to be mainly expressed by microglial cells found in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164682 15453089 221430 926 620 APP amyloid amyloid 13 1.0 be mainly expressed by microglial cells found in association with amyloid deposits regardless their ramified or activated morphology ( 71 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 164683 15453089 221431 11629 6493 LAMC2 CSF CSF 0 0.3 CSF levels of PGE 2 were increased in probable AD patients 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164684 15453089 221432 11629 6493 LAMC2 CSF CSF 17 0.3 a longitudinal study in which PGE 2 was measured in CSF samples obtained on at least 3 annual visits in 35 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164685 15453089 221433 11629 6493 LAMC2 CSF CSF 4 0.3 The study showed that CSF PGE 2 declines with the increasing dementia severity 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164686 15453089 221434 11629 6493 LAMC2 CSF CSF 3 0.3 Compared with controls CSF PGE 2 was higher in patients with mild memory impairment 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 164687 15453089 221435 17610 9605 PTGS2 COX COX-2-positive 12 0.0 is consistent with the slight increase in the number of COX-2-positive neurons at Braak stage A as well as with the 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164688 15453089 221435 17610 9605 PTGS2 COX COX-2-positive 25 0.0 Braak stage A as well as with the reduction in COX-2-positive neurons reported in patients with severe dementia and Braak end-stage 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164689 15453089 221436 17610 9605 PTGS2 COX-2 COX-2 4 4.4 The moderate increase in COX-2 expression and activity at very early stages of AD could 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164690 15453089 221437 17610 9605 PTGS2 COX-2 COX-2 3 4.4 Upregulation of neuronal COX-2 is associated with ischemia and excitotoxicity suggesting that COX-2 is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164691 15453089 221437 17610 9605 PTGS2 COX-2 COX-2 12 4.4 neuronal COX-2 is associated with ischemia and excitotoxicity suggesting that COX-2 is involved in neurotoxic mechanisms 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164692 15453089 221438 17610 9605 PTGS2 COX-2 COX-2 5 4.4 Increased susceptibility to excitotoxicity in COX-2 over-expressing neurons and neuroprotection by COX-2 inhibition has been shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164693 15453089 221438 17610 9605 PTGS2 COX-2 COX-2 11 4.4 susceptibility to excitotoxicity in COX-2 over-expressing neurons and neuroprotection by COX-2 inhibition has been shown in several experimental models ( 64 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164694 15453089 221439 17610 9605 PTGS2 COX-2 COX-2 2 4.4 Nonetheless increased COX-2 expression could be an adaptive reaction to pathological events such 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164695 15453089 221440 17610 9605 PTGS2 COX-2 COX-2 10 4.4 Taking into account the positive and negative effects of increased COX-2 activity and the emerging role of COX-2-derived PGs in brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164696 15453089 221440 17610 9605 PTGS2 COX-2 COX-2 33 4.4 is difficult to predict the final outcome of long-term therapeutic COX-2 inhibition 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164697 15453089 221440 17610 9605 PTGS2 COX COX-2-derived 17 0.0 effects of increased COX-2 activity and the emerging role of COX-2-derived PGs in brain function it is difficult to predict the 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 164698 15453089 221441 17610 9605 PTGS2 COX-2 COX-2 6 4.4 At present clinical trials of selective COX-2 inhibitors have not been as convincing as expected but these 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164699 15453089 221442 17610 9605 PTGS2 COX-2 COX-2 41 4.4 the peroxisome proliferator-activated receptor- gamma suggesting that selective inhibition of COX-2 may not be the optimal therapeutic strategy ( 64 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164700 15453089 221443 17610 9605 PTGS2 COX-2 COX-2 6 4.4 Since its discovery in early 1990s COX-2 has emerged as a major player in inflammatory reactions in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164701 15453089 221444 17610 9605 PTGS2 COX-2 COX-2 6 4.4 Evidence from several laboratories indicates that COX-2 is induced in various inflammatory settings is the main source 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164702 15453089 221445 17610 9605 PTGS2 COX-2 COX-2 2 4.4 By extension COX-2 expression in brain has been associated with pro-inflammatory activities thought 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164703 15453089 221446 17610 9605 PTGS2 COX-2 COX-2 14 4.4 should be borne in mind when considering the significance of COX-2 activity in brain diseases 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164704 15453089 221447 17610 9605 PTGS2 COX-2 COX-2 1 4.4 First COX-2 is expressed under normal conditions and contributes to fundamental brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164705 15453089 221451 17610 9605 PTGS2 COX-2 COX-2 17 4.4 the last decade the evidence of a direct role of COX-2 in neurodegenerative events is still controversial and further experimental and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164706 15453089 221451 17610 9605 PTGS2 COX-2 COX-2 40 4.4 are required to improve our knowledge of how and when COX-2 inhibition may have beneficial effects for patients suffering from inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164707 15453089 221453 17610 9605 PTGS2 COX-2 COX-2 17 4.4 neurons glia endothelial cells and infiltrating blood cells can express COX-2 in brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164708 15453089 221454 17610 9605 PTGS2 COX-2 COX-2 2 4.4 Over-expression of COX-2 in each of these cells may have different functional consequences 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164709 15453089 221454 17610 9605 PTGS2 COX-2 COX-2 26 4.4 outcome is likely to depend on the prevailing product of COX-2 activity including PGs with different functions and free radicals 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164710 15453089 221455 17610 9605 PTGS2 COX-2 COX-2 12 4.4 particularly susceptible to damage caused by free radicals generated through COX-2 peroxidase activity whereas glial cells are more resistant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164711 15453089 221456 17610 9605 PTGS2 COX-2 COX-2 5 4.4 Specific signals seem responsible for COX-2 induction and/or and or over-expression in particular cell types such 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164712 15453089 221458 17610 9605 PTGS2 COX-2 COX-2 7 4.4 The beneficial effects of specific and non-specific COX-2 inhibitors in several experimental models and epidemiological studies are an 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164713 15453089 221458 17610 9605 PTGS2 COX-2 COX-2 25 4.4 studies are an indirect proof of the causative role of COX-2 in neurodegeneration as COX-independent mechanisms cannot be excluded 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 164714 15453089 221458 17610 9605 PTGS2 COX COX-independent 29 0.0 proof of the causative role of COX-2 in neurodegeneration as COX-independent mechanisms cannot be excluded 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 168299 15507874 225815 22078 11777 TGM1 TGASE TGase 1 1.3 Transglutaminase (TGase)2 TGase 2 is an enzyme that is widely used in many 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 168300 15507874 225816 22078 11777 TGM1 TGASE TGase 4 1.3 Many reports showed that TGase 2 is aberrantly activated in tissues and cells and contributes 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 168301 15507874 225817 22078 11777 TGM1 TGASE TGase 3 1.3 In most cases TGase 2 appears to be a factor in the formation of 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 168302 15507874 225818 22078 11777 TGM1 TGASE TGase 14 1.3 such as celiac disease arthritis lupus and amyotrophic lateral sclerosis TGase 2 is involved in the generation of autoantibodies 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 168303 15507874 225819 22078 11777 TGM1 TGASE TGase 10 1.3 the possibility that inappropriate expression and/or and or presentation of TGase 2 to T cells might contribute to these diseases in 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 168304 15507874 225820 22078 11777 TGM1 TGASE TGase 6 1.3 We and others have found that TGase 2 expression is also increased in the inflammation process 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 168305 15507874 225821 22078 11777 TGM1 TGASE Tgase 9 1.3 Furthermore we also demonstrated a reversal of inflammation by Tgase inhibition 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 168306 15507874 225822 22078 11777 TGM1 TGASE TGase 7 1.3 This review will examine a possibility of TGase inhibitors as therapeutic agents in a variety of inflammatory diseases 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 168688 15512862 226133 20996 11179 SOD1 ALS ALS 3 1.2 Amyotrophic lateral sclerosis (ALS) ALS is a fatal paralytic neurodegenerative disorder 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000822418971594751<>ScoreDetail__5468|IGFALS|0.000180973638173373__11179|SOD1|0.000822418971594751__ 0 0 0 0 0 168689 15512862 226134 20996 11179 SOD1 ALS ALS 3 1.2 Experimental models of ALS such as the transgenic rodents expressing mutant superoxide dimutase-1 are 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000822418971594751<>ScoreDetail__5468|IGFALS|0.000180973638173373__11179|SOD1|0.000822418971594751__ 0 0 0 0 0 168690 15512862 226134 20996 11179 SOD1 ALS ALS 22 1.2 dimutase-1 are playing a pivotal role in our understanding of ALS pathogenesis and in our testing of new therapeutic interventions aimed 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000822418971594751<>ScoreDetail__5468|IGFALS|0.000180973638173373__11179|SOD1|0.000822418971594751__ 0 0 0 0 0 168691 15512862 226135 20996 11179 SOD1 ALS ALS 13 1.2 as a significant pathogenic factor in several neurodegenerative diseases including ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000822418971594751<>ScoreDetail__5468|IGFALS|0.000180973638173373__11179|SOD1|0.000822418971594751__ 0 0 0 0 0 168692 15512862 226136 20996 11179 SOD1 ALS ALS 26 1.2 and genetic interventions to be tested in experimental models of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000822418971594751<>ScoreDetail__5468|IGFALS|0.000180973638173373__11179|SOD1|0.000822418971594751__ 0 0 0 0 0 168693 15512862 226137 20996 11179 SOD1 ALS ALS 22 1.2 scientific basis for the development of effective neuroprotective therapies for ALS and Behavior Columbia University New York NY 10032 USA 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000822418971594751<>ScoreDetail__5468|IGFALS|0.000180973638173373__11179|SOD1|0.000822418971594751__ 0 0 0 0 0 161097 15571972 216578 20996 11179 SOD1 ALS ALS 11 1.0 crucial for lethal disorders such as amyotrophic lateral sclerosis (ALS) ALS and Huntington's disease (HD) HD for which no pharmacological or 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974281109189134<>ScoreDetail__5468|IGFALS|0.000886173363494322__11179|SOD1|0.000974281109189134__ 0 0 0 0 0 161098 15571972 216600 5854 21528 DIABLO SMAC Smac 55 1.3 see Blum et al. 2001 such as cytochrome c Smac/Diablo Smac Diablo or Apoptosis Inducing Factor (AIF; AIF Wang et al. 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161099 15571972 216600 480 8768 AIFM1 AIF AIF 60 0.6 cytochrome c Smac/Diablo Smac Diablo or Apoptosis Inducing Factor (AIF; AIF Wang et al. 2003a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161100 15571972 216620 4772 26515 COQ10A Q10 Q10 18 0.9 genetic mouse models such as suberoylanilide hydroxamic acid or coenzyme Q10 may or not modulate the presence of aggregates ( Hockly 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161101 15571972 216625 926 620 APP amyloid amyloid 16 1.0 work suggesting that tetracyclines can inhibit the formation of _amp_#x3b2 -amyloid aggregates and are able to disassemble preformed fibrils ( Forloni 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 161102 15571972 216642 20177 10935 SLC18A2 VMAT2 VMAT2 24 1.3 to compromise the activity of the vesicular monoamine transporter (VMAT2; VMAT2 Yang et al. 2003 that could promote chemical toxicity of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161103 15571972 216643 20996 11179 SOD1 ALS ALS 3 1.0 Amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974281109189134<>ScoreDetail__5468|IGFALS|0.000886173363494322__11179|SOD1|0.000974281109189134__ 0 0 0 0 0 161104 15571972 216644 20996 11179 SOD1 ALS ALS 15 1.0 reported a beneficial effect of minocycline in mouse models of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974281109189134<>ScoreDetail__5468|IGFALS|0.000886173363494322__11179|SOD1|0.000974281109189134__ 0 0 0 0 0 161105 15571972 216645 20996 11179 SOD1 SOD SOD 11 1.0 therapeutic efficacy of the antibiotic has been tested in the SOD G93A (10_amp_#x2013;50 10_amp_#x2013 50 mg/kg mg kg i.p Van Den 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161106 15571972 216645 20996 11179 SOD1 SOD SOD 30 1.0 al. 2002 and Zhu et al. 2002 and in the SOD G37R (1 1 g/kg g kg in diet Kriz et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161107 15571972 216647 20996 11179 SOD1 SOD SOD 20 1.0 against the neurotoxicity of CSF coming from patients carrying the SOD D90A mutation ( Tikka et al. 2002 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161108 15571972 216647 11629 6493 LAMC2 CSF CSF 14 0.0 the protective effect that minocycline exerted against the neurotoxicity of CSF coming from patients carrying the SOD D90A mutation ( Tikka 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161109 15571972 216650 3353 1368 CA1 CA1 CA1 17 0.0 of minocycline increased the number of surviving neurons in the CA1 pyramidal cell layer of gerbils submitted to a global ischemia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161110 15571972 216658 10731 6149 ITGAM CD11b CD11b 12 1.0 proliferation activation of resting microglial cells as revealed by CD11b/OX-42, CD11b OX-42 MAC-2 or isolectine-B4 staining ( Dommergues et al. 2003 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161111 15571972 216658 11780 6563 LGALS3 MAC-2 MAC-2 13 0.2 of resting microglial cells as revealed by CD11b/OX-42, CD11b OX-42 MAC-2 or isolectine-B4 staining ( Dommergues et al. 2003 _amp_#x2014 45 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161112 15571972 216665 480 8768 AIFM1 AIF AIF 35 0.6 the cytosolic release of apoptogenic factors such as cytochrome c AIF or Smac/Diablo Smac Diablo mediating caspase-dependent and -independent cell death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161113 15571972 216665 5854 21528 DIABLO SMAC Smac 37 1.3 of apoptogenic factors such as cytochrome c AIF or Smac/Diablo Smac Diablo mediating caspase-dependent and -independent cell death ( Matsuki et 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161114 15571972 216666 1576 990 BCL2 Bcl-2 Bcl-2 13 2.1 been recently shown to up-regulate expression of the anti-apoptotic protein Bcl-2 ( Wang et al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161115 15571972 216667 1576 990 BCL2 Bcl-2 Bcl-2 15 2.1 thus the activation_amp_#x2014 of Bid a pro-apoptotic protein of the Bcl-2 family ( Wang et al. 2003a _amp_#x2014 10 mg/kg mg 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161116 15571972 216672 20996 11179 SOD1 ALS ALS 8 1.0 Minocycline is being tested in HD PD and ALS patients ( URL 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974281109189134<>ScoreDetail__5468|IGFALS|0.000886173363494322__11179|SOD1|0.000974281109189134__ 0 0 0 0 0 161117 15571972 216673 20996 11179 SOD1 ALS ALS 21 1.0 any efficient therapies for devastating disorders such as HD and ALS these therapeutical trials are justified in these circumstances 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974281109189134<>ScoreDetail__5468|IGFALS|0.000886173363494322__11179|SOD1|0.000974281109189134__ 0 0 0 0 0 161118 15571972 216680 20996 11179 SOD1 ALS ALS 7 1.0 A trial is also in progress for ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974281109189134<>ScoreDetail__5468|IGFALS|0.000886173363494322__11179|SOD1|0.000974281109189134__ 0 0 0 0 0 161119 15571972 216681 20996 11179 SOD1 ALS ALS 14 1.0 that minocycline is safe and well tolerated by patients with ALS with few side effects 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974281109189134<>ScoreDetail__5468|IGFALS|0.000886173363494322__11179|SOD1|0.000974281109189134__ 0 0 0 0 0 161120 15571972 216687 20996 11179 SOD1 ALS ALS 29 1.0 these deleterious events have been or are being tested in ALS or HD patients ( Huntington Study Group 2001 Huntington Study 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974281109189134<>ScoreDetail__5468|IGFALS|0.000886173363494322__11179|SOD1|0.000974281109189134__ 0 0 0 0 0 161121 15571972 216690 20996 11179 SOD1 SOD1 SOD1 20 1.0 supplements has been shown to be very effective in the SOD1 G37R mouse model of ALS with a major increase of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161122 15571972 216690 20996 11179 SOD1 ALS ALS 25 1.0 be very effective in the SOD1 G37R mouse model of ALS with a major increase of the mice life span of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974281109189134<>ScoreDetail__5468|IGFALS|0.000886173363494322__11179|SOD1|0.000974281109189134__ 0 0 0 0 0 161123 15571972 216692 20996 11179 SOD1 ALS ALS 13 1.0 with both creatine and minocycline which are clinically tested in ALS patients as a sole therapy significantly delayed disease onset and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974281109189134<>ScoreDetail__5468|IGFALS|0.000886173363494322__11179|SOD1|0.000974281109189134__ 0 0 0 0 0 161124 15571972 216692 20996 11179 SOD1 SOD1 SOD1 27 1.0 sole therapy significantly delayed disease onset and increased survival of SOD1 G93A mice ( Zhang et al. 2003b as compared to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161125 15571972 216693 4772 26515 COQ10A Q10 Q10 13 0.9 communication reported the potential interest to combine minocycline and coenzyme Q10 in the R6/2 R6 2 HD model ( Carreras et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161126 15571972 216709 20996 11179 SOD1 ALS ALS 26 1.0 worth to be tested in neurodegenerative disorders such as HD ALS and PD 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974281109189134<>ScoreDetail__5468|IGFALS|0.000886173363494322__11179|SOD1|0.000974281109189134__ 0 0 0 0 0 161141 15572176 216716 20996 11179 SOD1 ALS ALS 18 1.9 upper and lower motor neurons and degenerating descending tracts of ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161142 15572176 216717 20996 11179 SOD1 ALS ALS 3 1.9 Reactive astrocytes in ALS contain protein inclusions express inflammatory makers such as the inducible 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161143 15572176 216717 14535 7873 NOS2A iNOS iNOS 19 2.7 such as the inducible forms of nitric oxide synthase (iNOS) iNOS and cyclooxygenase (COX-2), COX-2 display nitrotyrosine immunoreactivity and downregulate the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161144 15572176 216717 17610 9605 PTGS2 COX-2 COX-2 22 1.0 forms of nitric oxide synthase (iNOS) iNOS and cyclooxygenase (COX-2), COX-2 display nitrotyrosine immunoreactivity and downregulate the glutamate transporter EAAT2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161145 15572176 216717 20017 10940 SLC1A2 EAAT2 EAAT2 31 2.8 (COX-2), COX-2 display nitrotyrosine immunoreactivity and downregulate the glutamate transporter EAAT2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161146 15572176 216718 20996 11179 SOD1 ALS ALS 23 1.9 in the induction and propagation of motor neuron loss in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161147 15572176 216722 14373 7808 NGF NGF NGF 12 1.2 astrocytes secrete pro-apoptotic mediators such as nerve growth factor (NGF) NGF or Fas-ligand a mechanism that may serve to eliminate vulnerable 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161148 15572176 216722 7333 11920 FAS FAS Fas-ligand 14 0.6 pro-apoptotic mediators such as nerve growth factor (NGF) NGF or Fas-ligand a mechanism that may serve to eliminate vulnerable motor neurons 11 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000976658452517106<>ScoreDetail__11920|FAS|0.000976658452517106__3594|FASN|0.000580842750026402__ 0 0 0 0 0 161149 15572176 216723 20996 11179 SOD1 ALS ALS 12 1.9 understanding of the interactions between motor neurons and glia in ALS may lead to a more accurate theory of the pathogenesis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161150 15572176 216727 20996 11179 SOD1 ALS ALS 3 1.9 Amyotrophic lateral sclerosis (ALS) ALS is a neurodegenerative disease originally described by Charcot in 1869 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161151 15572176 216729 20996 11179 SOD1 ALS ALS 23 1.9 subtle changes in other cell types that may contribute to ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161152 15572176 216730 20996 11179 SOD1 ALS ALS 12 1.9 review we will consider the origin of reactive astrogliosis in ALS and how reactive changes in astrocytes may contribute to the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161153 15572176 216730 20996 11179 SOD1 ALS ALS 26 1.9 changes in astrocytes may contribute to the progressive nature of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161154 15572176 216731 20996 11179 SOD1 ALS ALS 3 1.9 About 10% of ALS cases show familial inheritance 20% of which are caused by 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161155 15572176 216731 20996 11179 SOD1 SOD1 SOD-1 23 2.4 mutations in the gene encoding copper zinc superoxide dismutase (SOD-1) SOD-1 106 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161156 15572176 216732 20996 11179 SOD1 ALS ALS 7 1.9 An important clue to the pathogenesis of ALS was provided by the development of several strains of different 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161157 15572176 216732 20996 11179 SOD1 SOD1 SOD-1 32 2.4 the disease carrying the expression of high levels of mutated SOD-1 genes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161158 15572176 216733 20996 11179 SOD1 SOD1 SOD-1 3 2.4 Toxicity of mutant SOD-1 involves a dominant gain-of-function rather than simply diminished superoxide-scavenging activity 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161159 15572176 216734 20996 11179 SOD1 SOD1 SOD-1 8 2.4 Spinal motor neurons express high levels of mutant SOD-1 which might explain the selective vulnerability of these neurons 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161160 15572176 216735 20996 11179 SOD1 ALS ALS-linked 5 1.9 However current evidence indicates that ALS-linked SOD-1 mutations must be expressed in both neuronal and non-neuronal 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161161 15572176 216735 20996 11179 SOD1 SOD1 SOD-1 6 2.4 However current evidence indicates that ALS-linked SOD-1 mutations must be expressed in both neuronal and non-neuronal cells 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161162 15572176 216736 20996 11179 SOD1 SOD1 SOD-1 23 2.4 spinal cord nerve or skeletal muscle are required for mutated SOD-1 to initiate neurodegeneration in ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161163 15572176 216736 20996 11179 SOD1 ALS ALS 28 1.9 muscle are required for mutated SOD-1 to initiate neurodegeneration in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161164 15572176 216737 20996 11179 SOD1 ALS ALS 23 1.9 mice composed of mixtures of normal cells and cells expressing ALS mutant SOD-1 showed that motor neuron degeneration is not necessarily 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161165 15572176 216737 20996 11179 SOD1 SOD1 SOD-1 25 2.4 of mixtures of normal cells and cells expressing ALS mutant SOD-1 showed that motor neuron degeneration is not necessarily associated with 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161166 15572176 216737 20996 11179 SOD1 SOD1 SOD-1 39 2.4 neuron degeneration is not necessarily associated with the expression of SOD-1 mutations in the motor neuron per se but rather with 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161167 15572176 216742 8254 4235 GFAP GFAP GFAP 36 2.5 processes with increased content of glial fibrillary acidic protein (GFAP) GFAP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161168 15572176 216747 20996 11179 SOD1 ALS ALS 52 1.9 it is not considered as a primary pathogenic element in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161169 15572176 216749 20996 11179 SOD1 ALS ALS 10 1.9 Extensive reviews have been recently published about the pathogenesis of ALS 12 25 and 110 the role of microglia and inflammatory 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161170 15572176 216749 20996 11179 SOD1 ALS ALS 26 1.9 and 110 the role of microglia and inflammatory cells in ALS 83 and the immune function of astrocytes 31 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161171 15572176 216751 20996 11179 SOD1 ALS ALS 9 1.9 Understanding of the interactions between neurons and glia in ALS may help to explain the progressive nature of ALS 2 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161172 15572176 216751 20996 11179 SOD1 ALS ALS 18 1.9 in ALS may help to explain the progressive nature of ALS 2 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161173 15572176 216752 20996 11179 SOD1 ALS ALS 3 1.9 Astrocyte pathology in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161174 15572176 216753 20996 11179 SOD1 ALS ALS 13 1.9 reaction typically surrounds both upper and lower motor neurons in ALS patients 59 71 87 90 and 120 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161175 15572176 216756 20996 11179 SOD1 ALS ALS 3 1.9 Reactive astrocytes in ALS show increased immunoreactivity for GFAP and the calcium binding protein 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161176 15572176 216756 8254 4235 GFAP GFAP GFAP 8 2.5 Reactive astrocytes in ALS show increased immunoreactivity for GFAP and the calcium binding protein S100_amp_#x3b2 85 and express inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161177 15572176 216756 17610 9605 PTGS2 COX-2 COX-2 24 1.0 binding protein S100_amp_#x3b2 85 and express inflammatory makers such as COX-2 81 iNOS and neuronal NOS 5 and 115 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161178 15572176 216756 14535 7873 NOS2A iNOS iNOS 28 2.7 S100_amp_#x3b2 85 and express inflammatory makers such as COX-2 81 iNOS and neuronal NOS 5 and 115 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161179 15572176 216756 14533 7872 NOS1 NOS NOS 31 2.7 express inflammatory makers such as COX-2 81 iNOS and neuronal NOS 5 and 115 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000725093975995573<>ScoreDetail__7873|NOS2A|0.000725093975995573__7872|NOS1|0.000651188823231834__ 0 0 0 0 0 161180 15572176 216758 20996 11179 SOD1 ALS ALS 15 1.9 changes has been described in the different animal models of ALS including mice and rats carrying different SOD-1 mutations 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161181 15572176 216758 20996 11179 SOD1 SOD1 SOD-1 22 2.4 animal models of ALS including mice and rats carrying different SOD-1 mutations 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161182 15572176 216759 20996 11179 SOD1 SOD1 SOD-1 8 2.4 In the case of mice expressing the G85R SOD-1 mutation astrocytes display major morphological and functional changes characterized by 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161183 15572176 216759 20996 11179 SOD1 SOD1 SOD1-containing 22 1.9 major morphological and functional changes characterized by the appearance of SOD1-containing aggregates and decreased expression of glial glutamate transporter GLT-1 18 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161184 15572176 216759 20017 10940 SLC1A2 GLT-1 GLT-1 31 2.8 of SOD1-containing aggregates and decreased expression of glial glutamate transporter GLT-1 18 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161185 15572176 216761 20996 11179 SOD1 SOD1 SOD-1 10 2.4 However the selective expression of the equivalent murine of G86R SOD-1 mutation in astroglia under the control of a GFAP promoter 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161186 15572176 216761 8254 4235 GFAP GFAP GFAP 19 2.5 G86R SOD-1 mutation in astroglia under the control of a GFAP promoter failed to induce motor neuron loss and disease 52 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161187 15572176 216761 20996 11179 SOD1 SOD1 SOD-1 39 2.4 and disease 52 indicating that glial pathology induced by mutant SOD-1 is not sufficient to initiate neurodegeneration 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161188 15572176 216763 20996 11179 SOD1 SOD1 SOD-1 5 2.4 Thus the selective expression of SOD-1 mutations in glial cells cannot explain per se the striking 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161189 15572176 216765 19294 10496 S100A6 S100A6 S100A6 14 1.4 G93A mice also upregulate the expression of the calcium-binding protein S100A6 63 as well as iNOS and become immunoreactive for nitrotyrosine 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161190 15572176 216765 14535 7873 NOS2A iNOS iNOS 21 2.7 expression of the calcium-binding protein S100A6 63 as well as iNOS and become immunoreactive for nitrotyrosine 3 and 116 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161191 15572176 216766 12359 6876 MAPK14 p38 p38 19 1.2 late stages of the disease express the activated form of p38 mitogen-activated protein kinase 130 which is stimulated by nitric oxide 1 JUMiner_v2.2 1 0 0 2 6871 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6871|MAPK1|0.000639856512201015<>ScoreDetail__1189|AHSA1|0.000242160067804819__6878|MAPK4|0.000591562451351772__6871|MAPK1|0.000639856512201015__6876|MAPK14|0.000638642931508193__ 0 0 0 0 0 161192 15572176 216767 20996 11179 SOD1 SOD1 SOD-1 18 2.4 earlier and more evident astrocytic alterations compared to the G93A SOD-1 mice 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161193 15572176 216769 20017 10940 SLC1A2 GLT-1 GLT-1 24 2.8 the neuropil and with a striking focal loss of the GLT-1 glutamate transporter in the ventral horn 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161194 15572176 216770 20996 11179 SOD1 ALS ALS 16 1.9 pathology of the disease indicate that astrocytic activation occurs in ALS both in humans and animal models of the disease with 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161195 15572176 216773 20996 11179 SOD1 SOD1 SOD-1 12 2.4 present protein aggregates such as Lewy body-like hyaline inclusions containing SOD-1 are not restricted to motor neurons but are also abundant 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161196 15572176 216776 20996 11179 SOD1 ALS ALS 5 1.9 The origin of astrocytosis in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161197 15572176 216777 20996 11179 SOD1 ALS ALS 1 1.9 Symptomatic ALS mice develop a typical _amp_#x201c isomorphic_amp_#x201d gliosis characterized by proliferative 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161198 15572176 216781 20996 11179 SOD1 ALS ALS 13 1.9 difficult to define the underlying causes of astrocytosis occurring in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161199 15572176 216782 20996 11179 SOD1 ALS ALS 22 1.9 might illustrate some of the mechanisms causing astrocyte reactivity in ALS 3.1 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161200 15572176 216784 20996 11179 SOD1 ALS ALS 0 1.9 ALS and related neurodegenerative diseases are closely associated with the aging 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161201 15572176 216786 8254 4235 GFAP GFAP GFAP 25 2.5 number of astrocytes 95 and 111 and the upregulation of GFAP and calcium-binding protein S100_amp_#x3b2 expression 138 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161202 15572176 216787 8254 4235 GFAP GFAP GFAP 30 2.5 in motor neurons and increased number of process-bearing astrocytes over-expressing GFAP in the anterior horn 28 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161203 15572176 216792 20996 11179 SOD1 ALS ALS 24 1.9 neurons may constitute a potential mechanism for astrocyte activation in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161204 15572176 216794 7333 11920 FAS FAS Fas 19 0.6 by motor neurons in response to trophic factor deprivation 35 Fas pathway activation 101 or loading with zinc-deficient SOD-1 36 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000976658452517106<>ScoreDetail__11920|FAS|0.000976658452517106__3594|FASN|0.000580842750026402__ 0 0 0 0 0 161205 15572176 216794 20996 11179 SOD1 SOD1 SOD-1 29 2.4 deprivation 35 Fas pathway activation 101 or loading with zinc-deficient SOD-1 36 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161206 15572176 216796 8254 4235 GFAP GFAP GFAP 25 2.5 changes characterized by the appearance of process-bearing cells displaying intense GFAP iNOS and nitrotyrosine immunoreactivity 19 and 20 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161207 15572176 216796 14535 7873 NOS2A iNOS iNOS 26 2.7 characterized by the appearance of process-bearing cells displaying intense GFAP iNOS and nitrotyrosine immunoreactivity 19 and 20 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161208 15572176 216797 10676 6121 IRF6 LPS LPS 8 0.6 A similar phenotype was induced by bacterial lipopolysaccharide (LPS), LPS a well-known inflammatory stimulus to glial cells 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 161209 15572176 216798 10676 6121 IRF6 LPS LPS 0 0.6 LPS stimulated iNOS expression and nitrotyrosine formation suggesting a role for 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 161210 15572176 216798 14535 7873 NOS2A iNOS iNOS 2 2.7 LPS stimulated iNOS expression and nitrotyrosine formation suggesting a role for peroxynitrite in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161211 15572176 216800 8332 4274 GJA1 CX43 Cx43 11 1.3 example astrocytes are extensively coupled by gap junctions of the Cx43 connexin subtype which allows intercellular diffusion of ions and signaling 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161212 15572176 216801 14533 7872 NOS1 NOS NOS 6 2.7 In cultured astrocytes the induction of NOS by pro-inflammatory stimulus or the exposure of astrocyte monolayers to 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000725093975995573<>ScoreDetail__7873|NOS2A|0.000725093975995573__7872|NOS1|0.000651188823231834__ 0 0 0 0 0 161213 15572176 216806 8254 4235 GFAP GFAP GFAP 8 2.5 This is followed by a sustained increase in GFAP synthesis lasting for several days 129 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161214 15572176 216807 14533 7872 NOS1 NOS NOS 26 2.7 histocompatibility complex-encoded antigens 89 interferon gamma 70 and 89 and NOS 70 have been found elevated in motor neurons after nerve 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000725093975995573<>ScoreDetail__7873|NOS2A|0.000725093975995573__7872|NOS1|0.000651188823231834__ 0 0 0 0 0 161215 15572176 216809 9905 5438 IFNG IFN IFN-G 4 1.6 Cytokines such as interferon-_amp_#x3b3 (IFN-_amp_#x3b3;) IFN-_amp_#x3b3 are among the most potent inducers of class II MHC 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000623608692722399<>ScoreDetail__5438|IFNG|0.000473318848524925__5417|IFNA1|0.000623608692722399__ 0 0 0 0 0 161216 15572176 216809 9353 4931 HLA-A MHC MHC 14 1.5 IFN-_amp_#x3b3 are among the most potent inducers of class II MHC expression in astrocytes 31 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161217 15572176 216810 9353 4931 HLA-A MHC MHC 12 1.5 cytokines neurotransmitters and neuropeptides are known to induce class II MHC suggesting a scenario in which damaged motor neurons releasing different 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161218 15572176 216811 20996 11179 SOD1 SOD1 SOD-1 24 2.4 showing that astrocyte and microglia activation around motor neurons in SOD-1 G93A mice occurs after the onset of distal axon degeneration 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161219 15572176 216813 20996 11179 SOD1 SOD1 SOD-1 15 2.4 for motor neurons modulating astrocytes reactivity was provided in G93A SOD-1 mice expressing increased levels of insulin growth factor-1 (IGF-1) IGF-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161220 15572176 216813 9939 5464 IGF1 IGF1 IGF-1 24 0.3 SOD-1 mice expressing increased levels of insulin growth factor-1 (IGF-1) IGF-1 in spinal motor neurons and skeletal muscle 67 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161221 15572176 216815 9939 5464 IGF1 IGF1 IGF-1 15 0.3 whether these effects are due to an increased release of IGF-1 to the surrounding neuropil targeting glial cells or to a 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161222 15572176 216816 20996 11179 SOD1 ALS ALS 28 1.9 elicit a secondary glial response resembling astrocytic changes in presymptomatic ALS mouse and rat models 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161223 15572176 216822 20996 11179 SOD1 ALS ALS 3 1.9 In this perspective ALS might be caused in part by a defective crosstalk between 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161224 15572176 216823 20996 11179 SOD1 ALS ALS 6 1.9 Neurotoxic potential of reactive astrocytes in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161225 15572176 216824 20996 11179 SOD1 ALS ALS 13 1.9 emphasized the involvement of astrocyte dysfunction in the pathogenesis of ALS through different synergistic mechanisms 4.1 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161226 15572176 216826 20996 11179 SOD1 ALS ALS 1 1.9 Many ALS patients have elevated glutamate levels in cerebrospinal fluid and a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161227 15572176 216826 20017 10940 SLC1A2 EAAT2 EAAT2 19 2.8 fluid and a selective reduction of the astrocytic glutamate transporter EAAT2 (GLT1), GLT1 giving support to the excitotoxic hypothesis of motor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161228 15572176 216826 20017 10940 SLC1A2 GLT1 GLT1 20 2.8 a selective reduction of the astrocytic glutamate transporter EAAT2 (GLT1), GLT1 giving support to the excitotoxic hypothesis of motor neuron degeneration 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161229 15572176 216828 20996 11179 SOD1 ALS ALS 3 1.9 In patients with ALS EAAT2 transporters are decreased or defective 108 and 114 which 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161230 15572176 216828 20017 10940 SLC1A2 EAAT2 EAAT2 4 2.8 In patients with ALS EAAT2 transporters are decreased or defective 108 and 114 which is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161231 15572176 216829 20017 10940 SLC1A2 EAAT2 EAAT2 4 2.8 Significant loss of the EAAT2 transporters has also been documented in the spinal cord of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161232 15572176 216829 20996 11179 SOD1 SOD1 SOD-1 15 2.4 transporters has also been documented in the spinal cord of SOD-1 G85R transgenic mice 18 and G93A transgenic rats 62 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161233 15572176 216831 20018 10941 SLC1A3 EAAT1 EAAT1 3 1.3 In contrast neither EAAT1 nor EAAT2 transporters seem to be affected in presymptomatic or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161234 15572176 216831 20017 10940 SLC1A2 EAAT2 EAAT2 5 2.8 In contrast neither EAAT1 nor EAAT2 transporters seem to be affected in presymptomatic or symptomatic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161235 15572176 216831 20996 11179 SOD1 SOD1 SOD1 19 1.9 be affected in presymptomatic or symptomatic mice carrying the G93A SOD1 mutation and are characterized by less pronounced tardy astrocyte reactivity 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161236 15572176 216832 20996 11179 SOD1 ALS ALS 20 1.9 the significant reduction in the ability to transport glutamate in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161237 15572176 216833 20017 10940 SLC1A2 EAAT2 EAAT2 8 2.8 The presence of aberrant mRNA splice variants for EAAT2 in ALS has been hypothesized as a putative cause of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161238 15572176 216833 20996 11179 SOD1 ALS ALS 10 1.9 The presence of aberrant mRNA splice variants for EAAT2 in ALS has been hypothesized as a putative cause of EAAT2 loss 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161239 15572176 216833 20017 10940 SLC1A2 EAAT2 EAAT2 19 2.8 in ALS has been hypothesized as a putative cause of EAAT2 loss 6 and 79 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161240 15572176 216834 20996 11179 SOD1 ALS ALS 36 1.9 of astrocytosis suggesting that the loss of glutamate transporters in ALS may be secondary to astrocytic activation 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161241 15572176 216841 20996 11179 SOD1 ALS ALS 5 1.9 For example reactive astrocytes in ALS express COX-2 an enzyme that catalyzes the synthesis of the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161242 15572176 216841 17610 9605 PTGS2 COX-2 COX-2 7 1.0 For example reactive astrocytes in ALS express COX-2 an enzyme that catalyzes the synthesis of the inflammatory prostaglandin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161243 15572176 216842 20996 11179 SOD1 ALS ALS 2 1.9 Treatment of ALS mice with the COX-2 inhibitor Celecoxib delayed the onset of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161244 15572176 216842 17610 9605 PTGS2 COX-2 COX-2 6 1.0 Treatment of ALS mice with the COX-2 inhibitor Celecoxib delayed the onset of the disease and increased 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161245 15572176 216845 20996 11179 SOD1 ALS ALS 1 1.9 In ALS neuroinflammatory changes can be observed through the entire motor system 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161246 15572176 216846 20996 11179 SOD1 ALS ALS 14 1.9 activation and its expression of some inflammatory mediators described in ALS the pathophysiological role of relevant cytokines and chemokines has remained 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161247 15572176 216847 10463 6018 IL6 IL-6 IL-6 8 1.6 For example in the CNS interleukin-1_amp_#x3b2 (IL-1_amp_#x3b2;) IL-1_amp_#x3b2 and IL-6 exert a powerful regulation of glial cells 109 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161248 15572176 216848 20996 11179 SOD1 ALS ALS 31 1.9 in diverse forms of neurodegeneration which could be relevant in ALS pathophysiology 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161249 15572176 216849 10463 6018 IL6 IL-6 IL-6 3 1.6 Proinflammatory IL-1_amp_#x3b2 and IL-6 are synthesized by neuroglia during epileptic activity 105 the response 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161250 15572176 216851 14535 7873 NOS2A iNOS iNOS 5 2.7 Interestingly cytokine signaling can induce iNOS COX-2 and NMDA receptor subunit phosphorylation with different consequences in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161251 15572176 216851 17610 9605 PTGS2 COX-2 COX-2 6 1.0 Interestingly cytokine signaling can induce iNOS COX-2 and NMDA receptor subunit phosphorylation with different consequences in glial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161252 15572176 216852 14535 7873 NOS2A iNOS iNOS 2 2.7 Activation of iNOS in astrocytes by IL-1_amp_#x3b2 potentiates NMDA-mediated neurotoxicity in mixed cortical 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161253 15572176 216853 22551 11892 TNF TNF TNF-A 8 1.2 Activation of murine astrocytes with tumour necrosis factor-alpha (TNF-_amp_#x3b1;), TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IFN_amp_#x3b3 induces IL-6 COX-2 and iNOS and makes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161254 15572176 216853 10463 6018 IL6 IL-6 IL-6 13 1.6 with tumour necrosis factor-alpha (TNF-_amp_#x3b1;), TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IFN_amp_#x3b3 induces IL-6 COX-2 and iNOS and makes the cells vulnerable to undergo 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161255 15572176 216853 17610 9605 PTGS2 COX-2 COX-2 14 1.0 tumour necrosis factor-alpha (TNF-_amp_#x3b1;), TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IFN_amp_#x3b3 induces IL-6 COX-2 and iNOS and makes the cells vulnerable to undergo apoptosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161256 15572176 216853 14535 7873 NOS2A iNOS iNOS 16 2.7 factor-alpha (TNF-_amp_#x3b1;), TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IFN_amp_#x3b3 induces IL-6 COX-2 and iNOS and makes the cells vulnerable to undergo apoptosis in response 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161257 15572176 216853 7333 11920 FAS FAS Fas 28 0.6 makes the cells vulnerable to undergo apoptosis in response to Fas ligand (FasL) FasL 39 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000976658452517106<>ScoreDetail__11920|FAS|0.000976658452517106__3594|FASN|0.000580842750026402__ 0 0 0 0 0 161258 15572176 216853 7334 11936 FASLG FasL FasL 30 2.2 vulnerable to undergo apoptosis in response to Fas ligand (FasL) FasL 39 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161259 15572176 216854 10676 6121 IRF6 LPS LPS-treated 23 0.6 has been recently reported in the spinal cord of chronically LPS-treated mutant SOD1 mice 88 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 161260 15572176 216854 20996 11179 SOD1 SOD1 SOD1 25 1.9 recently reported in the spinal cord of chronically LPS-treated mutant SOD1 mice 88 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161261 15572176 216855 10463 6018 IL6 IL-6 IL-6 6 1.6 Activated astrocytes are potent producers of IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161262 15572176 216856 10463 6018 IL6 IL-6 IL-6 1 1.6 While IL-6 can promote survival and protect neurons from degeneration it can 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161263 15572176 216857 20996 11179 SOD1 ALS ALS 27 1.9 a role in initiating and modulating the inflammatory mechanisms in ALS explaining relevant features of the astrocyte pathology 4.3 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161264 15572176 216859 20996 11179 SOD1 ALS ALS 9 1.9 Free radical damage is a characteristic of pathologically affected ALS tissues 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161265 15572176 216861 14535 7873 NOS2A iNOS iNOS 4 2.7 In particular induction of iNOS by LPS or cytokines seems to be required for astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161266 15572176 216861 10676 6121 IRF6 LPS LPS 6 0.6 In particular induction of iNOS by LPS or cytokines seems to be required for astrocytes to promote 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 161267 15572176 216864 10676 6121 IRF6 LPS LPS 22 0.6 monolayers of astrocytes that were first exposed to peroxynitrite or LPS 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 161268 15572176 216866 10676 6121 IRF6 LPS LPS 14 0.6 the motor neurons plated on astrocytes pretreated with peroxynitrite or LPS undergo apoptosis over the next 24 h 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 161269 15572176 216869 14535 7873 NOS2A iNOS iNOS 2 2.7 Inhibition of iNOS by nitro--arginine methyl ester and low concentrations of aminoguanidine prevented 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161270 15572176 216872 20996 11179 SOD1 SOD1 SOD-1 19 2.4 cultured motor neurons undergoing apoptosis 35 and 36 in mutant SOD-1 mice 42 and 116 and in sporadic and familial cases 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161271 15572176 216872 20996 11179 SOD1 ALS ALS 33 1.9 42 and 116 and in sporadic and familial cases of ALS 1 8 43 and 115 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161272 15572176 216874 20996 11179 SOD1 SOD SOD-mimetic 5 1.9 Mn-TBAP is a membrane permeant SOD-mimetic and peroxynitrite scavenger 40 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161273 15572176 216876 20996 11179 SOD1 ALS ALS 4 1.9 Thus reactive astrocytes in ALS would not only impair neuronal excitability and neurotransmission but they 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161274 15572176 216878 7334 11936 FASLG FasL FasL 10 2.2 Cytokines and trophic factors produced by activated astrocytes such as FasL TNF-_amp_#x3b1 and NGF are capable of activating death receptors expressed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161275 15572176 216878 22551 11892 TNF TNF TNF-A 11 1.2 and trophic factors produced by activated astrocytes such as FasL TNF-_amp_#x3b1 and NGF are capable of activating death receptors expressed in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161276 15572176 216878 14373 7808 NGF NGF NGF 13 1.2 factors produced by activated astrocytes such as FasL TNF-_amp_#x3b1 and NGF are capable of activating death receptors expressed in the diseased 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161277 15572176 216879 20996 11179 SOD1 ALS ALS 12 1.9 could play a role in motor neuron loss observed in ALS without the direct involvement of the immune system 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161278 15572176 216881 7334 11936 FASLG FasL FasL 1 2.2 Although FasL is induced in reactive astrocytes as well as in microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161279 15572176 216881 20996 11179 SOD1 ALS ALS 29 1.9 44 and 45 little is known about its expression in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161280 15572176 216882 7333 11920 FAS FAS Fas 3 0.6 Motor neurons co-express Fas and FasL during the embryonic period of naturally occurring cell 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000976658452517106<>ScoreDetail__11920|FAS|0.000976658452517106__3594|FASN|0.000580842750026402__ 0 0 0 0 0 161281 15572176 216882 7334 11936 FASLG FasL FasL 5 2.2 Motor neurons co-express Fas and FasL during the embryonic period of naturally occurring cell death however 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161282 15572176 216882 7333 11920 FAS FAS Fas 28 0.6 in motoneuron survival were observed in mutant mice deficient for Fas signaling 133 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000976658452517106<>ScoreDetail__11920|FAS|0.000976658452517106__3594|FASN|0.000580842750026402__ 0 0 0 0 0 161283 15572176 216883 7333 11920 FAS FAS Fas 2 0.6 In contrast Fas signaling has been implicated in motor neuron death induced by 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000976658452517106<>ScoreDetail__11920|FAS|0.000976658452517106__3594|FASN|0.000580842750026402__ 0 0 0 0 0 161284 15572176 216884 20996 11179 SOD1 ALS ALS-linked 7 1.9 Furthermore motor neurons from transgenic mice overexpressing ALS-linked SOD mutations G37R G85R or G93A display an increased susceptibility 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161285 15572176 216884 20996 11179 SOD1 SOD SOD 8 1.9 Furthermore motor neurons from transgenic mice overexpressing ALS-linked SOD mutations G37R G85R or G93A display an increased susceptibility to 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161286 15572176 216884 7333 11920 FAS FAS Fas 19 0.6 mutations G37R G85R or G93A display an increased susceptibility to Fas signaling 99 and 101 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000976658452517106<>ScoreDetail__11920|FAS|0.000976658452517106__3594|FASN|0.000580842750026402__ 0 0 0 0 0 161287 15572176 216885 7333 11920 FAS FAS Fas 5 0.6 The apoptotic pathway activated by Fas seems to be specific for motor neurons requiring co-activation of 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000976658452517106<>ScoreDetail__11920|FAS|0.000976658452517106__3594|FASN|0.000580842750026402__ 0 0 0 0 0 161288 15572176 216885 3532 1509 CASP8 caspase-8 caspase-8 16 2.0 seems to be specific for motor neurons requiring co-activation of caspase-8 and p38 as well as the production of nitric oxide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161289 15572176 216885 12359 6876 MAPK14 p38 p38 18 1.2 be specific for motor neurons requiring co-activation of caspase-8 and p38 as well as the production of nitric oxide by neuronal 1 JUMiner_v2.2 1 0 0 2 6871 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6871|MAPK1|0.000639856512201015<>ScoreDetail__1189|AHSA1|0.000242160067804819__6878|MAPK4|0.000591562451351772__6871|MAPK1|0.000639856512201015__6876|MAPK14|0.000638642931508193__ 0 0 0 0 0 161290 15572176 216885 14533 7872 NOS1 NOS NOS 29 2.7 as well as the production of nitric oxide by neuronal NOS 101 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000725093975995573<>ScoreDetail__7873|NOS2A|0.000725093975995573__7872|NOS1|0.000651188823231834__ 0 0 0 0 0 161291 15572176 216886 14373 7808 NGF NGF NGF 11 1.2 apoptotic candidate released by astrocytes is nerve growth factor (NGF) NGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161292 15572176 216887 14373 7808 NGF NGF NGF 1 1.2 Clearly NGF is critical for the differentiation and survival of specific neuronal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161293 15572176 216888 14373 7808 NGF NGF NGF 1 1.2 While NGF can signal through activation of the high affinity TrkA receptor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161294 15572176 216888 14738 8031 NTRK1 TRKA TrkA 10 1.9 While NGF can signal through activation of the high affinity TrkA receptor it also can activate the non-selective neurotrophin receptor p75 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161295 15572176 216888 22562 11917 TNFRSF1B p75 p75 20 1.8 TrkA receptor it also can activate the non-selective neurotrophin receptor p75 NTR a member of the tumor necrosis factor receptor superfamily 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161296 15572176 216888 22562 11917 TNFRSF1B NTR NTR 21 0.5 receptor it also can activate the non-selective neurotrophin receptor p75 NTR a member of the tumor necrosis factor receptor superfamily 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161297 15572176 216889 14373 7808 NGF NGF NGF 9 1.2 Motor neurons are generally thought to be unresponsive to NGF because they lack the specific TrkA receptor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161298 15572176 216889 14738 8031 NTRK1 TRKA TrkA 15 1.9 to be unresponsive to NGF because they lack the specific TrkA receptor 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161299 15572176 216890 1624 1033 BDNF BDNF BDNF 12 0.3 do respond to other members of the neurotrophin family including BDNF NT-3 and NT-4/5 NT-4 5 123 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161300 15572176 216890 14727 8023 NTF3 NT3 NT-3 13 0.3 respond to other members of the neurotrophin family including BDNF NT-3 and NT-4/5 NT-4 5 123 11 JUMiner_v2.2 1 0 0 2 8023 TotalCon:3<>8020|NT3|4877|Complete__11186|SORT1|6272|Complete__8023|NTF3|4908|Complete__<>AvaiableGeneRif=3<>BEST:8023|NTF3|0.000650438590427304<>ScoreDetail__8023|NTF3|0.000650438590427304__11186|SORT1|0.000392299309843807__8020|NT3|4.95327411418948e-05__ 0 0 0 0 0 161301 15572176 216890 14728 8024 NTF4 NT-4/5 NT-4/5 15 1.3 other members of the neurotrophin family including BDNF NT-3 and NT-4/5 NT-4 5 123 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161302 15572176 216890 14728 8024 NTF4 NT4 NT-4 15 1.3 members of the neurotrophin family including BDNF NT-3 and NT-4/5 NT-4 5 123 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161303 15572176 216891 22562 11917 TNFRSF1B p75 p75 2 1.8 Signaling through p75 NTR in the absence of the corresponding Trk receptor has 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161304 15572176 216891 22562 11917 TNFRSF1B NTR NTR 3 0.5 Signaling through p75 NTR in the absence of the corresponding Trk receptor has been 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161305 15572176 216891 14738 8031 NTRK1 TRK Trk 11 1.9 Signaling through p75 NTR in the absence of the corresponding Trk receptor has been shown to promote apoptosis in specific neuronal 2 JUMiner_v2.2 1 0 0 2 8031 TotalCon:2<>8031|NTRK1|4914|Complete__12012|TPM3|7170|Complete__<>AvaiableGeneRif=2<>BEST:8031|NTRK1|0.000756977805938748<>ScoreDetail__8031|NTRK1|0.000756977805938748__12012|TPM3|0.000311348658606196__ 0 0 0 0 0 161306 15572176 216892 22562 11917 TNFRSF1B p75 p75 3 1.8 Motor neurons express p75 NTR during the embryonic period of naturally occurring cell death 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161307 15572176 216892 22562 11917 TNFRSF1B NTR NTR 4 0.5 Motor neurons express p75 NTR during the embryonic period of naturally occurring cell death when 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161308 15572176 216893 22562 11917 TNFRSF1B p75 p75 1 1.8 Although p75 NTR is not present in mature motor neurons the receptor 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161309 15572176 216893 22562 11917 TNFRSF1B NTR NTR 2 0.5 Although p75 NTR is not present in mature motor neurons the receptor can 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161310 15572176 216894 22562 11917 TNFRSF1B p75 p75 1 1.8 Moreover p75 NTR is found in motor neurons of ALS patients 80 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161311 15572176 216894 22562 11917 TNFRSF1B NTR NTR 2 0.5 Moreover p75 NTR is found in motor neurons of ALS patients 80 and 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161312 15572176 216894 20996 11179 SOD1 ALS ALS 9 1.9 Moreover p75 NTR is found in motor neurons of ALS patients 80 and 121 suggesting that re-expression of the receptor 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161313 15572176 216894 22562 11917 TNFRSF1B p75 p75 31 1.8 receptor might modulate the death of neurons in damaged areas p75 NTR expression can be also observed on reactive astrocytes microglia 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161314 15572176 216894 22562 11917 TNFRSF1B NTR NTR 32 0.5 might modulate the death of neurons in damaged areas p75 NTR expression can be also observed on reactive astrocytes microglia and 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161315 15572176 216894 14373 7808 NGF NGF NGF 55 1.2 in chronic active MS lesions suggesting an additional role for NGF in regulating the immune response in glial cells 135 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161316 15572176 216895 14373 7808 NGF NGF NGF 15 1.2 expression and release of several growth factors and cytokines including NGF 33 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161317 15572176 216896 14373 7808 NGF NGF NGF 1 1.2 Increased NGF levels have been shown in rodent CNS following experimental lesions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161318 15572176 216897 14373 7808 NGF NGF NGF 2 1.2 Expression of NGF receptors in active multiple sclerosis lesions suggests a role for 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161319 15572176 216897 14373 7808 NGF NGF NGF 13 1.2 receptors in active multiple sclerosis lesions suggests a role for NGF in regulating the autoimmune response at both immune and glial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161320 15572176 216898 14373 7808 NGF NGF NGF 8 1.2 However little is known about the expression of NGF in ALS although increased NGF levels were reported in muscle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161321 15572176 216898 20996 11179 SOD1 ALS ALS 10 1.9 However little is known about the expression of NGF in ALS although increased NGF levels were reported in muscle of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161322 15572176 216898 14373 7808 NGF NGF NGF 13 1.2 known about the expression of NGF in ALS although increased NGF levels were reported in muscle of ALS patients 72 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161323 15572176 216898 20996 11179 SOD1 ALS ALS 20 1.9 ALS although increased NGF levels were reported in muscle of ALS patients 72 and 127 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161324 15572176 216899 14373 7808 NGF NGF NGF 5 1.2 Thus it is conceivable that NGF signaling between astrocytes and p75 NTR -expressing motor neurons may 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161325 15572176 216899 22562 11917 TNFRSF1B p75 p75 10 1.8 Thus it is conceivable that NGF signaling between astrocytes and p75 NTR -expressing motor neurons may contribute to the induction of 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161326 15572176 216899 22562 11917 TNFRSF1B NTR NTR 11 0.5 it is conceivable that NGF signaling between astrocytes and p75 NTR -expressing motor neurons may contribute to the induction of neuronal 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161327 15572176 216899 20996 11179 SOD1 ALS ALS 24 1.9 neurons may contribute to the induction of neuronal apoptosis in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161328 15572176 216900 14373 7808 NGF NGF NGF 8 1.2 We have recently found a prominent increase in NGF immunoreactivity in the neuropil of the anterior horn in symptomatic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161329 15572176 216900 22562 11917 TNFRSF1B p75 p75 26 1.8 horn in symptomatic mice carrying the G93A mutation coincident with p75 NTR expression in motor neurons 93 suggesting that increased NGF 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161330 15572176 216900 22562 11917 TNFRSF1B NTR NTR 27 0.5 in symptomatic mice carrying the G93A mutation coincident with p75 NTR expression in motor neurons 93 suggesting that increased NGF production 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161331 15572176 216900 14373 7808 NGF NGF NGF 38 1.2 p75 NTR expression in motor neurons 93 suggesting that increased NGF production may parallel the development of astrocytosis in ALS and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161332 15572176 216900 20996 11179 SOD1 ALS ALS 47 1.9 increased NGF production may parallel the development of astrocytosis in ALS and contribute to motor neuron death 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161333 15572176 216901 14373 7808 NGF NGF NGF 11 1.2 also found that reactive astrocytes secrete high molecular forms of NGF which could correspond to the precursors forms of NGF (pro-NGF) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161334 15572176 216901 14373 7808 NGF NGF NGF 20 1.2 of NGF which could correspond to the precursors forms of NGF (pro-NGF) pro-NGF 92 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161335 15572176 216903 22562 11917 TNFRSF1B p75 p75 9 1.8 Some isoforms of pro-NGF bind with high affinity to p75 NTR and thus induces a specific apoptotic signal even in 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161336 15572176 216903 22562 11917 TNFRSF1B NTR NTR 10 0.5 Some isoforms of pro-NGF bind with high affinity to p75 NTR and thus induces a specific apoptotic signal even in cells 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161337 15572176 216903 22562 11917 TNFRSF1B p75 p75 23 1.8 induces a specific apoptotic signal even in cells expressing both p75 NTR and TrkA receptors 76 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161338 15572176 216903 22562 11917 TNFRSF1B NTR NTR 24 0.5 a specific apoptotic signal even in cells expressing both p75 NTR and TrkA receptors 76 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161339 15572176 216903 14738 8031 NTRK1 TRKA TrkA 26 1.9 apoptotic signal even in cells expressing both p75 NTR and TrkA receptors 76 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161340 15572176 216904 14373 7808 NGF NGF NGF 9 1.2 Two recent reports further support a role for a NGF/p75 NGF p75 NTR apoptotic pathway in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161341 15572176 216904 22562 11917 TNFRSF1B p75 p75 9 1.8 recent reports further support a role for a NGF/p75 NGF p75 NTR apoptotic pathway in ALS 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161342 15572176 216904 22562 11917 TNFRSF1B NTR NTR 10 0.5 reports further support a role for a NGF/p75 NGF p75 NTR apoptotic pathway in ALS 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161343 15572176 216904 20996 11179 SOD1 ALS ALS 14 1.9 role for a NGF/p75 NGF p75 NTR apoptotic pathway in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161344 15572176 216905 20996 11179 SOD1 SOD SOD 2 1.9 Survival of SOD G93A mice is significantly increased by systemic treatment with an 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161345 15572176 216905 22562 11917 TNFRSF1B p75 p75 21 1.8 with an antisense peptide nucleic acid construct that targets the p75 NTR gene and inhibits its expression 132 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161346 15572176 216905 22562 11917 TNFRSF1B NTR NTR 22 0.5 an antisense peptide nucleic acid construct that targets the p75 NTR gene and inhibits its expression 132 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161347 15572176 216906 20996 11179 SOD1 SOD1 SOD1 17 1.9 increase in survival was reported in double transgenic mice expressing SOD1 G93A but lacking p75 NTR 73 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161348 15572176 216906 22562 11917 TNFRSF1B p75 p75 21 1.8 reported in double transgenic mice expressing SOD1 G93A but lacking p75 NTR 73 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161349 15572176 216906 22562 11917 TNFRSF1B NTR NTR 22 0.5 in double transgenic mice expressing SOD1 G93A but lacking p75 NTR 73 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161350 15572176 216911 22562 11917 TNFRSF1B p75 p75 5 1.8 For example the re-expression of p75 NTR and neuronal NOS may help to determine which neurons 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161351 15572176 216911 22562 11917 TNFRSF1B NTR NTR 6 0.5 For example the re-expression of p75 NTR and neuronal NOS may help to determine which neurons survive 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161352 15572176 216911 14533 7872 NOS1 NOS NOS 9 2.7 For example the re-expression of p75 NTR and neuronal NOS may help to determine which neurons survive or undergo apoptosis 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000725093975995573<>ScoreDetail__7873|NOS2A|0.000725093975995573__7872|NOS1|0.000651188823231834__ 0 0 0 0 0 161353 15572176 216915 7334 11936 FASLG FasL FasL 5 2.2 Similarly increased production of either FasL or NGF does not induce motor neuron apoptosis unless nitric 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161354 15572176 216915 14373 7808 NGF NGF NGF 7 1.2 Similarly increased production of either FasL or NGF does not induce motor neuron apoptosis unless nitric oxide is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161355 15572176 216915 22562 11917 TNFRSF1B p75 p75 20 1.8 induce motor neuron apoptosis unless nitric oxide is produced or p75 NTR is expressed in those neurons 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161356 15572176 216915 22562 11917 TNFRSF1B NTR NTR 21 0.5 motor neuron apoptosis unless nitric oxide is produced or p75 NTR is expressed in those neurons 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161357 15572176 216916 20996 11179 SOD1 ALS ALS 37 1.9 triggers a progressive motor neuron disease with the characteristics of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161358 15572176 216918 20996 11179 SOD1 ALS ALS 12 1.9 that these mechanisms are somehow critically and irreversibly disrupted in ALS 6 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161359 15572176 216920 20996 11179 SOD1 ALS ALS 3 1.9 The pathology of ALS is characterized by widespread signs of neuronal and astrocyte dysfunction 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161360 15572176 216923 20996 11179 SOD1 ALS ALS 5 1.9 Because reactive astrocytes occurring in ALS may spread the phenotypic transformation to astrocytes located in adjacent 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161361 15572176 216927 20996 11179 SOD1 ALS ALS 9 1.9 Deciphering the interactions between motor neurons and glia in ALS may reveal the basis for the progressive pathogenesis of the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161362 15572176 216929 20996 11179 SOD1 ALS ALS 10 1.9 Proposed pathogenic steps involving astrocyte to motor neuron signaling in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000806718321836908<>ScoreDetail__5468|IGFALS|0.000350557049558202__11179|SOD1|0.000806718321836908__ 0 0 0 0 0 161363 15572176 216931 14533 7872 NOS1 nNOS nNOS 20 2.7 damage in motor neuron A which upregulates the expression of nNOS p75 NTR Fas cytokines and trophic factors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161364 15572176 216931 22562 11917 TNFRSF1B p75 p75 21 1.8 in motor neuron A which upregulates the expression of nNOS p75 NTR Fas cytokines and trophic factors 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000666833375010419<>ScoreDetail__9527|PSIP1|0.000531902698489121__2557|CUX1|0.000533263397150101__10876|SIGLEC7|0.000666833375010419__11917|TNFRSF1B|0.000620940217989651__ 0 0 0 0 0 161365 15572176 216931 22562 11917 TNFRSF1B NTR NTR 22 0.5 motor neuron A which upregulates the expression of nNOS p75 NTR Fas cytokines and trophic factors 3 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 161366 15572176 216931 7333 11920 FAS FAS Fas 24 0.6 neuron A which upregulates the expression of nNOS p75 NTR Fas cytokines and trophic factors 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000976658452517106<>ScoreDetail__11920|FAS|0.000976658452517106__3594|FASN|0.000580842750026402__ 0 0 0 0 0 161367 15572176 216936 14373 7808 NGF NGF NGF 16 1.2 by producing NO cytokines and pro apoptotic mediators such as NGF or FasL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 161368 15572176 216936 7334 11936 FASLG FasL FasL 18 2.2 NO cytokines and pro apoptotic mediators such as NGF or FasL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155370 15649489 206195 20996 11179 SOD1 ALS ALS 19 1.7 the pathogenesis of motoneuron death in amyotrophic lateral sclerosis (ALS) ALS both in humans and transgenic mouse models 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155371 15649489 206196 17031 9232 PPARA PPAR PPARs 3 2.2 Peroxisome proliferator-activated receptors (PPARs) PPARs are involved in the inflammatory process 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155372 15649489 206197 17031 9232 PPARA PPAR PPAR- 2 2.2 Agonists of PPAR- -_amp_#x3b3 and -_amp_#x3b4 show anti-inflammatory effects both in vitro and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155373 15649489 206198 17034 9236 PPARG PPAR PPAR-G 11 2.2 the therapeutic effect of pioglitazone a peroxisome proliferator-activated receptor-gamma (PPAR-_amp_#x3b3;) PPAR-_amp_#x3b3 agonist in the G93A SOD1 transgenic mouse model of ALS 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155374 15649489 206198 20996 11179 SOD1 SOD1 SOD1 16 1.7 a peroxisome proliferator-activated receptor-gamma (PPAR-_amp_#x3b3;) PPAR-_amp_#x3b3 agonist in the G93A SOD1 transgenic mouse model of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155375 15649489 206198 20996 11179 SOD1 ALS ALS 21 1.7 PPAR-_amp_#x3b3 agonist in the G93A SOD1 transgenic mouse model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155376 15649489 206200 3889 11919 CD40 CD40 CD-40 16 0.3 and it reduced gliosis as assessed by immunohistochemical staining for CD-40 and GFAP 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155377 15649489 206200 8254 4235 GFAP GFAP GFAP 18 2.5 reduced gliosis as assessed by immunohistochemical staining for CD-40 and GFAP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155378 15649489 206201 14535 7873 NOS2A iNOS iNOS 3 3.2 Pioglitazone also reduced iNOS NF_amp_#x3ba -B and 3-nitrotyrosine immunoreactivity in the spinal cords of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155379 15649489 206202 20996 11179 SOD1 ALS ALS 11 1.7 results suggest that pioglitazone may have therapeutic potential for human ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155380 15649489 206204 20996 11179 SOD1 ALS ALS 3 1.7 Amyotrophic lateral sclerosis (ALS) ALS is one of the most common adult onset neurodegenerative diseases 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155381 15649489 206205 20996 11179 SOD1 SOD1 SOD1 23 1.7 the gene coding for copper_amp_#x2013 zinc superoxide dismutase 1 (SOD1) SOD1 in a subset of patients with autosomal dominant inherited ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155382 15649489 206205 20996 11179 SOD1 ALS ALS 33 1.7 SOD1 in a subset of patients with autosomal dominant inherited ALS ( Rosen et al. 1993 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155383 15649489 206207 20996 11179 SOD1 ALS ALS 14 1.7 demonstrated that activated microglia occur in transgenic mouse models of ALS ( Hall et al. 1998 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155384 15649489 206209 17031 9232 PPARA PPAR PPARs 4 2.2 The peroxisome proliferator-activated receptors (PPARs) PPARs are member of the nuclear receptor super family 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155385 15649489 206210 17031 9232 PPARA PPAR PPARs 0 2.2 PPARs are ligand dependent transcription factors that bind to specific peroxisome 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155386 15649489 206211 17031 9232 PPARA PPAR PPARs 0 2.2 PPARs have been implicated in insulin sensitivity adipocyte differentiation and inflammatory 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155387 15649489 206212 17031 9232 PPARA PPAR PPAR- 6 2.2 Numerous studies show that agonists of PPAR- -_amp_#x3b3 and -_amp_#x3b4 exert anti-inflammatory effects both in vitro and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155388 15649489 206213 17031 9232 PPARA PPAR PPARs 0 2.2 PPARs down-regulate proinflammatory cytokines and iNOS in both macrophages and microglial 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155389 15649489 206213 14535 7873 NOS2A iNOS iNOS 5 3.2 PPARs down-regulate proinflammatory cytokines and iNOS in both macrophages and microglial cells ( Colville-Nash et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155390 15649489 206214 17034 9236 PPARG PPAR PPAR-G 4 2.2 Previous studies showed that PPAR-_amp_#x3b3 agonists protect cerebellar granule cells from cytokine-induced apoptotic cell death 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155391 15649489 206217 14535 7873 NOS2A iNOS iNOS-positive 9 3.2 Pioglitazone treatment reduced activation of microglia reduced induction of iNOS-positive cells and less glial fibrillary acidic protein-positive cells in both 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 155392 15649489 206218 17034 9236 PPARG PPAR PPAR-G 7 2.2 We therefore examined whether an agonist of PPAR-_amp_#x3b3 an anti-inflammatory protein could delay or slow the disease process 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155393 15649489 206218 20996 11179 SOD1 SOD1 SOD1 21 1.7 could delay or slow the disease process in the G93A SOD1 transgenic mouse model of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155394 15649489 206218 20996 11179 SOD1 ALS ALS 26 1.7 disease process in the G93A SOD1 transgenic mouse model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155395 15649489 206221 20996 11179 SOD1 ALS ALS 3 1.7 G93A transgenic familial ALS mice (high high expresser line ( Gurney 1994 were obtained 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155396 15649489 206224 20996 11179 SOD1 SOD1 SOD1 2 1.7 Thirty-nine G93A SOD1 transgenic mice were randomly assigned to control (vehicle) vehicle and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155397 15649489 206225 20996 11179 SOD1 SOD1 SOD1 11 1.7 Actos was given in food at 1200 ppm to G93A SOD1 mice ( n = 18 and control mice ( n 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155398 15649489 206248 11763 6553 LEP LEP LEP 17 0.0 of a Nikon Eclipse E600 microscope equipped with a computer-controlled LEP BioPoint motorized stage a DEI-750 video camera a Dell Dimension 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155399 15649489 206257 3889 11919 CD40 CD40 CD40 5 0.3 The sections were immunostained with CD40 (Serotec), Serotec GFAP (DAKO), DAKO iNOS (Upstate, Upstate Waltham MA 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155400 15649489 206257 8254 4235 GFAP GFAP GFAP 7 2.5 The sections were immunostained with CD40 (Serotec), Serotec GFAP (DAKO), DAKO iNOS (Upstate, Upstate Waltham MA NF_amp_#x3ba B (Santa 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155401 15649489 206257 14535 7873 NOS2A iNOS iNOS 9 3.2 sections were immunostained with CD40 (Serotec), Serotec GFAP (DAKO), DAKO iNOS (Upstate, Upstate Waltham MA NF_amp_#x3ba B (Santa Santa Cruz CA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155402 15649489 206278 3889 11919 CD40 CD40 CD40 19 0.3 G93A mice and controls for immunoreactivity to the microglial marker CD40 and the astrocyte marker GFAP at 110 days of age 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155403 15649489 206278 8254 4235 GFAP GFAP GFAP 24 2.5 immunoreactivity to the microglial marker CD40 and the astrocyte marker GFAP at 110 days of age 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155404 15649489 206279 3889 11919 CD40 CD40 CD40 1 0.3 Both CD40 and GFAP immunoreactivities were decreased in pioglitazone-treated G93A mice as 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155405 15649489 206279 8254 4235 GFAP GFAP GFAP 3 2.5 Both CD40 and GFAP immunoreactivities were decreased in pioglitazone-treated G93A mice as compared to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155406 15649489 206280 14535 7873 NOS2A iNOS iNOS 0 3.2 iNOS NF_amp_#x3ba -B and nitrotyrosine immunoreactivity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155407 15649489 206281 14535 7873 NOS2A iNOS iNOS 9 3.2 Control diet fed G93A mice showed strong immunoreactivity for iNOS NF_amp_#x3ba -B and 3-nitrotyrosine 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155408 15649489 206282 14535 7873 NOS2A iNOS iNOS 6 3.2 Pioglitazone treatment reduced the immunoreactivity of iNOS NF_amp_#x3ba -B and 3-nitrotyrosine in the lumbar spinal cord sections 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155409 15649489 206284 20996 11179 SOD1 ALS ALS 11 1.7 is increasing evidence that inflammatory mechanisms play a role in ALS pathogenesis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155410 15649489 206286 14535 7873 NOS2A iNOS iNOS 6 3.2 IL-1_amp_#x3b2 tumor necrosis factor- and iNOS levels are increased in transgenic mouse models of ALS ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155411 15649489 206286 20996 11179 SOD1 ALS ALS 15 1.7 and iNOS levels are increased in transgenic mouse models of ALS ( Almer et al. 1999 Elliott 2001 Ghezzi et al. 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155412 15649489 206287 20996 11179 SOD1 ALS ALS 13 1.7 activation slowed disease progression in one transgenic mouse model of ALS ( Friedlander et al. 1998 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155413 15649489 206289 20996 11179 SOD1 SOD1 SOD1 10 1.7 Transcription profiling of the spinal cords of mice with G93A SOD1 mutations showed up-regulation of tumor necrosis factor- CD68 and caspase-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155414 15649489 206289 3901 1693 CD68 CD68 CD68 19 0.3 with G93A SOD1 mutations showed up-regulation of tumor necrosis factor- CD68 and caspase-1 mRNA at 11 weeks of age prior to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155415 15649489 206290 3900 1692 CD63 CD63 CD63 6 0.3 Furthermore markers of microgial activation including CD63 MAC-1 cathepsin-5 _amp_#x3b2 2_amp_#xa0 microglobulin C10C- and AGC1Q-_amp_#x3b2 are increased 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155416 15649489 206290 10731 6149 ITGAM MAC-1 MAC-1 7 1.0 Furthermore markers of microgial activation including CD63 MAC-1 cathepsin-5 _amp_#x3b2 2_amp_#xa0 microglobulin C10C- and AGC1Q-_amp_#x3b2 are increased at 1 JUMiner_v2.2 1 0 0 2 6155 TotalCon:2<>6149|ITGAM|3684|Complete__6155|ITGB2|3689|Complete__<>AvaiableGeneRif=2<>BEST:6155|ITGB2|0.000426792021660589<>ScoreDetail__6155|ITGB2|0.000426792021660589__6149|ITGAM|0.000369838903004933__ 0 0 0 0 0 155417 15649489 206291 10444 5993 IL1R1 IL1RA IL1-RA 3 0.0 IL-_amp_#x3b2 IL-1_amp_#x3b2 and IL1-RA are increased at 80 days and multiple caspase and death 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000183493733979586<>ScoreDetail__5993|IL1R1|0.000136263904125759__6000|IL1RN|0.000183493733979586__ 0 0 0 0 0 155418 15649489 206299 14535 7873 NOS2A iNOS iNOS-positive 4 3.2 It reduced induction of iNOS-positive cells and there was less glial fibrillary acidic protein-positive cells 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 155419 15649489 206300 17034 9236 PPARG PPAR PPAR-G 9 2.2 It was suggested that these effects were due to PPAR-_amp_#x3b3 activation an increase in inhibitory protein-_amp_#x3ba -_amp_#x3b2 expression and inhibition 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155420 15649489 206300 8569 16769 GORASP1 P65 P65 25 0.0 inhibition of translocation of nuclear factor _amp_#x3ba -_amp_#x3b2 _amp_#xa0 subunit P65 to the nucleus in the dopaminergic neurons and glial cells 1 JUMiner_v2.2 1 0 0 2 16769 TotalCon:2<>16769|GORASP1|64689|Complete__11509|SYT1|6857|Complete__<>AvaiableGeneRif=2<>BEST:16769|GORASP1|0.000327398191754602<>ScoreDetail__16769|GORASP1|0.000327398191754602__11509|SYT1|0.000159201867968584__ 0 0 0 0 0 155421 15649489 206301 14535 7873 NOS2A iNOS iNOS 4 3.2 This appears to block iNOS induction and NO-mediated toxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155422 15649489 206303 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x3b3 was originally characterized as a regulator of adipocyte differentiation and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155423 15649489 206304 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x3b3 was also shown to have a possible role in cell 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155424 15649489 206305 17034 9236 PPARG PPAR PPAR-G 6 2.2 These authors showed anti-inflammatory effect of PPAR-_amp_#x3b3 15d-PGJ 2 in a rat model of carrageenin-induced pleural inflammation 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155425 15649489 206309 17034 9236 PPARG PPAR PPAR-G 8 2.2 Our data suggest that the neuroprotective effect of PPAR-_amp_#x3b3 may stem from its role in inflammation however other roles 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155426 15649489 206309 17034 9236 PPARG PPAR PPAR-G 20 2.2 stem from its role in inflammation however other roles of PPAR-_amp_#x3b3 may have contributed 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155427 15649489 206310 17034 9236 PPARG PPAR PPAR-G 12 2.2 of pioglitazone is not known obviously those cells that express PPAR-_amp_#x3b3 _amp_#xa0 would be targeted 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155428 15649489 206311 20996 11179 SOD1 ALS ALS 20 1.7 may be an effective strategy for ameliorating the progression of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155429 15649489 206313 20996 11179 SOD1 ALS ALS 18 1.7 could readily become an agent worthy of testing in human ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00150977120752612<>ScoreDetail__5468|IGFALS|0.000376251034690345__11179|SOD1|0.00150977120752612__ 0 0 0 0 0 155430 15649489 206314 20996 11179 SOD1 SOD1 SOD1 11 1.7 The effect of pioglitazone treatment on motor performance in G93A SOD1 transgenic mice from 72 days to 140 days of age 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155431 15649489 206317 20996 11179 SOD1 SOD1 SOD1 9 1.7 ( Pioglitazone-treated G93A mice ( vehicle-treated G93A SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155432 15649489 206323 20996 11179 SOD1 SOD1 SOD1 13 1.7 of pioglitazone treatment on Nissl-stained neuronal cell count in G93A SOD1 transgenic mice at 110 days of age 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155433 15649489 206329 3889 11919 CD40 CD40 CD40 3 0.3 Pioglitazone treatment reduced CD40 (marker marker of microglial activation and GFAP (marker marker of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155434 15649489 206329 8254 4235 GFAP GFAP GFAP 9 2.5 Pioglitazone treatment reduced CD40 (marker marker of microglial activation and GFAP (marker marker of astrocytosis immunoreactivity in the ventral horn of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155435 15649489 206331 14535 7873 NOS2A iNOS iNOS 4 3.2 Fig 5._amp_#xa0 Pioglitazone treatment reduced iNOS NF_amp_#x3ba -B and 3-nitrotyrosine immunostaining in G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 155436 15649489 206332 14535 7873 NOS2A iNOS iNOS 1 3.2 Strong iNOS NF_amp_#x3ba -B and 3-nitrotyrosine immunoreactivities in motor neurons (arrow) arrow 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156440 15657392 207605 20996 11179 SOD1 ALS ALS 3 2.2 Amyotrophic lateral sclerosis (ALS) ALS is a progressive neurodegenerative disease characterized by a selective degeneration 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156441 15657392 207606 20996 11179 SOD1 ALS ALS 6 2.2 Although a significant proportion of familial ALS results from a toxic gain of function associated with dominant 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156442 15657392 207606 20996 11179 SOD1 SOD1 SOD1 17 2.5 results from a toxic gain of function associated with dominant SOD1 mutations the etiology of the disease and its specific cellular 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156443 15657392 207607 20996 11179 SOD1 SOD1 SOD1 24 2.5 isoform maintained muscle integrity and enhanced satellite cell activity in SOD1 transgenic mice inducing calcineurin-mediated regenerative pathways 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156444 15657392 207608 9939 5464 IGF1 IGF1 Igf-1 4 3.5 Muscle-specific expression of local Igf-1 (mIgf-1) mIgf-1 isoform also stabilized neuromuscular junctions reduced inflammation in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156445 15657392 207608 20996 11179 SOD1 SOD1 SOD1 23 2.5 in the spinal cord and enhanced motor neuronal survival in SOD1 mice delaying the onset and progression of the disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156446 15657392 207609 20996 11179 SOD1 SOD1 SOD1 15 2.5 as a primary target for the dominant action of inherited SOD1 mutation and suggest that muscle fibers provide appropriate factors such 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156447 15657392 207610 20996 11179 SOD1 ALS ALS 8 2.2 Abbreviations used in this paper AChR acetylcholine receptor ALS amyotrophic lateral sclerosis CnA calcineurin GFAP glial fibrillary acidic protein 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156448 15657392 207610 8254 4235 GFAP GFAP GFAP 14 2.5 paper AChR acetylcholine receptor ALS amyotrophic lateral sclerosis CnA calcineurin GFAP glial fibrillary acidic protein Igf insulin-like growth factor mIgf-1 local 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156449 15657392 207610 9939 5464 IGF1 IGF1 Igf-1 27 3.5 acidic protein Igf insulin-like growth factor mIgf-1 local isoform of Igf-1 MyHC myosin heavy chain SOD1 superoxide dismutase1 wt wild-type 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156450 15657392 207610 13948 7576 MYH6 MYHC MyHC 28 2.5 protein Igf insulin-like growth factor mIgf-1 local isoform of Igf-1 MyHC myosin heavy chain SOD1 superoxide dismutase1 wt wild-type 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156451 15657392 207610 13956 23212 MYH14 myosin myosin 29 2.2 Igf insulin-like growth factor mIgf-1 local isoform of Igf-1 MyHC myosin heavy chain SOD1 superoxide dismutase1 wt wild-type 1 JUMiner_v2.2 1 0 0 2 7609 TotalCon:8<>23212|MYH14|79784|Complete__7599|MYO1E|4643|Complete__7600|MYO1F|4542|No_GeneRif__7603|MYO5B|4645|Complete__7604|MYO5C|55930|No_GeneRif__7605|MYO6|4646|Complete__7608|MYO9A|4649|No_GeneRif__7609|MYO9B|4650|Complete__<>AvaiableGeneRif=5<>BEST:7609|MYO9B|0.000676728031648133<>ScoreDetail__7599|MYO1E|0.000213289169928736__7609|MYO9B|0.000676728031648133__7603|MYO5B|0.000208463623097769__23212|MYH14|0.00012646793134598__7605|MYO6|0.000449401478939413__ 0 0 0 0 0 156452 15657392 207610 20996 11179 SOD1 SOD1 SOD1 32 2.5 factor mIgf-1 local isoform of Igf-1 MyHC myosin heavy chain SOD1 superoxide dismutase1 wt wild-type 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156453 15657392 207612 20996 11179 SOD1 ALS ALS 3 2.2 Amyotrophic lateral sclerosis (ALS) ALS is a fatal neuromuscular disorder involving the degeneration of motor 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156454 15657392 207613 20996 11179 SOD1 SOD1 SOD1 5 2.5 Transgenic mice ubiquitously overexpressing human SOD1 mutants develop motor neuron disease resembling ALS ( Gurney et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156455 15657392 207613 20996 11179 SOD1 ALS ALS 12 2.2 ubiquitously overexpressing human SOD1 mutants develop motor neuron disease resembling ALS ( Gurney et al. 1994 and provide useful model to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156456 15657392 207614 20996 11179 SOD1 SOD1 SOD1 3 2.5 Notably restriction of SOD1 mutant expression selectively to post-natal motor neurons failed to produce 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156457 15657392 207614 20996 11179 SOD1 ALS ALS-associated 36 2.2 2002 suggesting that other cell types may be involved in ALS-associated neurodegeneration 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156458 15657392 207615 20996 11179 SOD1 SOD1 SOD1 8 2.5 Indeed analysis of chimeras generated between wild-type and SOD1 mutant mouse embryonic cells revealed that wild-type non neuronal cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156459 15657392 207615 20996 11179 SOD1 SOD1 SOD1 27 2.5 neuronal cells in adult chimeric animals extended the survival of SOD1 mutant motor neurons suggesting that the neurodegenerative action of mutant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156460 15657392 207615 20996 11179 SOD1 SOD1 SOD1 38 2.5 mutant motor neurons suggesting that the neurodegenerative action of mutant SOD1 may operate through a dominant paracrine activity emanating from nonneuronal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156461 15657392 207616 20996 11179 SOD1 SOD1 SOD1 12 2.5 is an untested component in the motor neurodegenerative effects of SOD1 mutations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156462 15657392 207618 9939 5464 IGF1 IGF1 Igf-1 6 3.5 Among these insulin-like growth factor 1 (Igf-1) Igf-1 has been implicated in anabolism of muscle and nerve tissues 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156463 15657392 207619 20996 11179 SOD1 SOD1 SOD1 6 2.5 In a recent study injection of SOD1 mutant mouse muscle with an adeno-associated virus carrying an Igf-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156464 15657392 207619 9939 5464 IGF1 IGF1 Igf-1 16 3.5 SOD1 mutant mouse muscle with an adeno-associated virus carrying an Igf-1 gene prolonged life and delayed disease progression ( Kaspar et 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156465 15657392 207621 9939 5464 IGF1 IGF1 Igf-1 9 3.5 However it is not clear from that study which Igf-1 isoform was used or whether the effects of Igf-1 expressed 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156466 15657392 207621 9939 5464 IGF1 IGF1 Igf-1 18 3.5 which Igf-1 isoform was used or whether the effects of Igf-1 expressed in motor neurons were cell autonomous 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156467 15657392 207622 9939 5464 IGF1 IGF1 Igf-1 4 3.5 Two major isoforms of Igf-1 originating from alternative splicing have been described differing in structure 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156468 15657392 207623 9939 5464 IGF1 IGF1 Igf-1 12 3.5 as circulating (class class 2 and local (class class 1 Igf-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156469 15657392 207624 9939 5464 IGF1 IGF1 Igf-1 0 3.5 Igf-1 class 2 transcripts predominate in the liver are highly growth 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156470 15657392 207626 9939 5464 IGF1 IGF1 Igf-1 7 3.5 The contribution to more localized accumulation of Igf-1 class 1 seems due to the combination of exon 1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156471 15657392 207627 9939 5464 IGF1 IGF1 Igf-1 6 3.5 To assess the effects of supplemental Igf-1 directly on atrophic SOD1 skeletal muscle we exploited a transgenic 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156472 15657392 207627 20996 11179 SOD1 SOD1 SOD1 10 2.5 To assess the effects of supplemental Igf-1 directly on atrophic SOD1 skeletal muscle we exploited a transgenic mouse expressing a full-length 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156473 15657392 207627 9939 5464 IGF1 IGF1 Igf-1 27 3.5 mouse expressing a full-length precursor of the local isoform of Igf-1 (mIgf-1) mIgf-1 that is normally induced transiently in response to 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156474 15657392 207628 13966 29823 MYL6B MLC MLC 4 0.6 Muscle restricted mIgf-1 transgene (MLC/mIgf-1) MLC mIgf-1 exerts its effects in an autocrine/paracrine autocrine paracrine manner 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156475 15657392 207628 9939 5464 IGF1 IGF1 Igf-1 19 3.5 autocrine paracrine manner circumventing the adverse side effects of systemic Igf-1 administration 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156476 15657392 207629 13966 29823 MYL6B MLC MLC 3 0.6 Expression of the MLC/mIgf-1, MLC mIgf-1 delivered either as an inherited transgene or somatically on 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156477 15657392 207629 38 22 AAVS1 AAV AAV 14 0.9 delivered either as an inherited transgene or somatically on an AAV vector induces muscle hypertrophy and strength and preserves regenerative capacity 1 JUMiner_v2.2 1 2 aav vector 0 0 0 0 0 0 0 0 156478 15657392 207630 20996 11179 SOD1 ALS ALS 16 2.2 skeletal muscle as a primary target in inherited forms of ALS by showing that localized expression of the coinherited MLC/mIgf-1 MLC 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156479 15657392 207630 13966 29823 MYL6B MLC MLC 25 0.6 ALS by showing that localized expression of the coinherited MLC/mIgf-1 MLC mIgf-1 transgene exclusively in the skeletal muscle of SOD1 mice 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156480 15657392 207630 20996 11179 SOD1 SOD1 SOD1 33 2.5 MLC/mIgf-1 MLC mIgf-1 transgene exclusively in the skeletal muscle of SOD1 mice counteracted the symptoms of ALS induced satellite cell activity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156481 15657392 207630 20996 11179 SOD1 ALS ALS 39 2.2 the skeletal muscle of SOD1 mice counteracted the symptoms of ALS induced satellite cell activity stabilized neuromuscular junctions and led to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156482 15657392 207630 20996 11179 SOD1 SOD1 SOD1 56 2.5 junctions and led to a reduction in astrocytosis in the SOD1 spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156483 15657392 207631 9939 5464 IGF1 IGF1 Igf-1 17 3.5 attenuation of motor neuronal degradation and underscore the importance of Igf-1 isoform selection when designing therapeutic strategies for ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156484 15657392 207631 20996 11179 SOD1 ALS ALS 25 2.2 importance of Igf-1 isoform selection when designing therapeutic strategies for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156485 15657392 207643 20996 11179 SOD1 SOD1 SOD1 15 2.5 the progression of the disease and enhances the survival of SOD1 mutant mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156486 15657392 207644 20996 11179 SOD1 SOD SOD 6 2.2 (a) a Western blot analysis of human SOD transgenic protein in wild-type (lane lane 1 MLC/mIgf-1 MLC mIgf-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156487 15657392 207644 13966 29823 MYL6B MLC MLC 13 0.6 human SOD transgenic protein in wild-type (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156488 15657392 207644 20996 11179 SOD1 SOD1 SOD1 16 2.5 wild-type (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lane lane 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156489 15657392 207644 20996 11179 SOD1 SOD1 SOD1 20 2.5 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lane lane 4 transgenic muscle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156490 15657392 207645 13966 29823 MYL6B MLC MLC 16 0.6 in skeletal muscle of wild-type (wt; wt lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156491 15657392 207645 20996 11179 SOD1 SOD1 SOD1 19 2.5 (wt; wt lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lane lane 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156492 15657392 207645 20996 11179 SOD1 SOD1 SOD1 23 2.5 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lane lane 4 transgenic mice in brain and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156493 15657392 207645 13966 29823 MYL6B MLC MLC 35 0.6 4 transgenic mice in brain and spinal cord of MLC/mIgf-1 MLC mIgf-1 (lanes lanes 5 and 7 and SOD1 /mIgf-1 mIgf-1 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156494 15657392 207645 20996 11179 SOD1 SOD1 SOD1 41 2.5 of MLC/mIgf-1 MLC mIgf-1 (lanes lanes 5 and 7 and SOD1 /mIgf-1 mIgf-1 (lanes lanes 6 and 8 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156495 15657392 207646 20996 11179 SOD1 SOD1 SOD1 9 2.5 (c) c Age of onset of disease symptoms average onset SOD1 ( n = 30 = 111 _amp_#177 1.8 SOD1 /mIgf-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156496 15657392 207646 20996 11179 SOD1 SOD1 SOD1 18 2.5 onset SOD1 ( n = 30 = 111 _amp_#177 1.8 SOD1 /mIgf-1 mIgf-1 ( n = 30 = 120.8 _amp_#177 1.0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156497 15657392 207646 20996 11179 SOD1 SOD1 SOD1 40 2.5 of the progression of the disease average of disease duration SOD1 ( n = 30 =12 _amp_#177 0.6 SOD1 /mIgf-1 mIgf-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156498 15657392 207646 20996 11179 SOD1 SOD1 SOD1 48 2.5 disease duration SOD1 ( n = 30 =12 _amp_#177 0.6 SOD1 /mIgf-1 mIgf-1 ( n = 30 = 32 _amp_#177 0.8 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156499 15657392 207646 20996 11179 SOD1 SOD1 SOD1 63 2.5 = 32 _amp_#177 0.8 (e) e survival analysis average survival SOD1 ( n = 30 = 123 _amp_#177 1.4 SOD1 /mIgf-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156500 15657392 207646 20996 11179 SOD1 SOD1 SOD1 72 2.5 survival SOD1 ( n = 30 = 123 _amp_#177 1.4 SOD1 /mIgf-1 mIgf-1 ( n = 30 = 152.8 _amp_#177 1.4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156501 15657392 207647 20996 11179 SOD1 SOD1 SOD1 12 2.5 mIgf-1 expression attenuates muscle wasting and promotes regenerative pathways in SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156502 15657392 207648 13966 29823 MYL6B MLC MLC 5 0.6 (a) a Histological analysis of wt MLC/mIgf-1, MLC mIgf-1 SOD1 and SOD1 /mIgf-1 mIgf-1 muscle at different age 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156503 15657392 207648 20996 11179 SOD1 SOD1 SOD1 6 2.5 (a) a Histological analysis of wt MLC/mIgf-1, MLC mIgf-1 SOD1 and SOD1 /mIgf-1 mIgf-1 muscle at different age and stage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156504 15657392 207648 20996 11179 SOD1 SOD1 SOD1 6 2.5 (a) a Histological analysis of wt MLC/mIgf-1, MLC mIgf-1 SOD1 and SOD1 /mIgf-1 mIgf-1 muscle at different age and stage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156505 15657392 207648 20996 11179 SOD1 SOD1 SOD1 8 2.5 a Histological analysis of wt MLC/mIgf-1, MLC mIgf-1 SOD1 and SOD1 /mIgf-1 mIgf-1 muscle at different age and stage of disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156506 15657392 207649 20996 11179 SOD1 SOD1 SOD1 20 2.5 the quadriceps underscores the relative attenuation of muscle atrophy in SOD1 /mIgf-1 mIgf-1 compared with SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156507 15657392 207649 20996 11179 SOD1 SOD1 SOD1 24 2.5 attenuation of muscle atrophy in SOD1 /mIgf-1 mIgf-1 compared with SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156508 15657392 207651 13966 29823 MYL6B MLC MLC 11 0.6 were obtained from quadriceps of wt (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lanes lanes 3 and 5 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156509 15657392 207651 20996 11179 SOD1 SOD1 SOD1 14 2.5 wt (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lanes lanes 3 and 5 and SOD1 /mIgf-1 mIgf-1 (lanes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156510 15657392 207651 20996 11179 SOD1 SOD1 SOD1 20 2.5 (lane lane 2 SOD1 (lanes lanes 3 and 5 and SOD1 /mIgf-1 mIgf-1 (lanes lanes 4 and 6 transgenic mice at 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156511 15657392 207653 20996 11179 SOD1 SOD1 SOD1 11 2.5 Immunofluorescence analysis of MyHC-fast performed on soleus muscles of wt SOD1 and SOD1 /mIgf-1 mIgf-1 before (80 80 d and after 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156512 15657392 207653 20996 11179 SOD1 SOD1 SOD1 11 2.5 Immunofluorescence analysis of MyHC-fast performed on soleus muscles of wt SOD1 and SOD1 /mIgf-1 mIgf-1 before (80 80 d and after 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156513 15657392 207653 20996 11179 SOD1 SOD1 SOD1 13 2.5 of MyHC-fast performed on soleus muscles of wt SOD1 and SOD1 /mIgf-1 mIgf-1 before (80 80 d and after symptom onset 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156514 15657392 207655 20996 11179 SOD1 SOD1 SOD1 4 2.5 (e) e Walk test of SOD1 (closed closed circles and SOD1 /mIgf-1 mIgf-1 (open open circles 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156515 15657392 207655 20996 11179 SOD1 SOD1 SOD1 8 2.5 (e) e Walk test of SOD1 (closed closed circles and SOD1 /mIgf-1 mIgf-1 (open open circles transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156516 15657392 207657 20996 11179 SOD1 SOD1 SOD1 8 2.5 Transgenic mIgf-1 expression induces chronic CnA-_amp_#223 1 expression in SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156517 15657392 207658 13966 29823 MYL6B MLC MLC 11 0.6 of CnA-_amp_#223 1 expression in wt (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156518 15657392 207658 20996 11179 SOD1 SOD1 SOD1 14 2.5 wt (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lane lane 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156519 15657392 207658 20996 11179 SOD1 SOD1 SOD1 18 2.5 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lane lane 4 transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156520 15657392 207661 20996 11179 SOD1 SOD1 SOD1 9 2.5 (c) c Immunofluorescence of transverse sections from quadriceps muscles of SOD1 and SOD /mIgf-1 mIgf-1 at paralysis stage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156521 15657392 207661 20996 11179 SOD1 SOD SOD 11 2.2 Immunofluorescence of transverse sections from quadriceps muscles of SOD1 and SOD /mIgf-1 mIgf-1 at paralysis stage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156522 15657392 207667 20996 11179 SOD1 SOD1 SOD1 7 2.5 Maintenance of the neuromuscular junction configuration in SOD1 /mIgf-1 mIgf-1 transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156523 15657392 207668 13966 29823 MYL6B MLC MLC 10 0.6 Immunofluorescent analysis of transverse sections from muscles of wt MLC/mIgf-1, MLC mIgf-1 SOD1 and SOD1 /mIgf-1 mIgf-1 transgenic mice at 123 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156524 15657392 207668 20996 11179 SOD1 SOD1 SOD1 11 2.5 of transverse sections from muscles of wt MLC/mIgf-1, MLC mIgf-1 SOD1 and SOD1 /mIgf-1 mIgf-1 transgenic mice at 123 d old 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156525 15657392 207668 20996 11179 SOD1 SOD1 SOD1 11 2.5 of transverse sections from muscles of wt MLC/mIgf-1, MLC mIgf-1 SOD1 and SOD1 /mIgf-1 mIgf-1 transgenic mice at 123 d old 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156526 15657392 207668 20996 11179 SOD1 SOD1 SOD1 13 2.5 sections from muscles of wt MLC/mIgf-1, MLC mIgf-1 SOD1 and SOD1 /mIgf-1 mIgf-1 transgenic mice at 123 d old alpha-bungarotoxin antibody 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156527 15657392 207668 20996 11179 SOD1 SOD1 SOD1 29 2.5 d old alpha-bungarotoxin antibody identified diffusion of AChR expression in SOD1 muscle (yellow yellow arrow whereas SOD /mIgf-1 mIgf-1 muscle maintained 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156528 15657392 207668 20996 11179 SOD1 SOD SOD 34 2.2 of AChR expression in SOD1 muscle (yellow yellow arrow whereas SOD /mIgf-1 mIgf-1 muscle maintained AChR clusters 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156529 15657392 207670 13966 29823 MYL6B MLC MLC 13 0.6 RNA samples from quadriceps of wt (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156530 15657392 207670 20996 11179 SOD1 SOD1 SOD1 16 2.5 wt (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lanes lanes 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156531 15657392 207670 20996 11179 SOD1 SOD1 SOD1 20 2.5 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lanes lanes 4 and 5 transgenic muscles at 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156532 15657392 207672 449 329 AGRN AGRIN agrin 4 1.0 (c) c Western blot of agrin from quadriceps of wt (lane lane 1 MLC/mIgf-1 MLC mIgf-1 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156533 15657392 207672 13966 29823 MYL6B MLC MLC 11 0.6 of agrin from quadriceps of wt (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156534 15657392 207672 20996 11179 SOD1 SOD1 SOD1 14 2.5 wt (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lane lane 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156535 15657392 207672 20996 11179 SOD1 SOD1 SOD1 18 2.5 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lane lane 4 transgenic muscles 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156536 15657392 207673 20996 11179 SOD1 SOD1 SOD1 0 2.5 SOD1 and SOD1 /mIgf-1 mIgf-1 mice were analyzed at comparable end-stage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156537 15657392 207673 20996 11179 SOD1 SOD1 SOD1 0 2.5 SOD1 and SOD1 /mIgf-1 mIgf-1 mice were analyzed at comparable end-stage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156538 15657392 207673 20996 11179 SOD1 SOD1 SOD1 2 2.5 SOD1 and SOD1 /mIgf-1 mIgf-1 mice were analyzed at comparable end-stage disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156539 15657392 207676 20996 11179 SOD1 SOD1 SOD1 13 2.5 surviving motor neurons in the ventral spinal cord of wild-type SOD1 and SOD1 /mIgf-1 mIgf-1 mice at different ages *P _lt_ 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156540 15657392 207676 20996 11179 SOD1 SOD1 SOD1 13 2.5 surviving motor neurons in the ventral spinal cord of wild-type SOD1 and SOD1 /mIgf-1 mIgf-1 mice at different ages *P _lt_ 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156541 15657392 207676 20996 11179 SOD1 SOD1 SOD1 15 2.5 neurons in the ventral spinal cord of wild-type SOD1 and SOD1 /mIgf-1 mIgf-1 mice at different ages *P _lt_ 0.001 **P 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156542 15657392 207677 8254 4235 GFAP GFAP GFAP 4 2.5 (b) b Immunofluorescence analysis identify GFAP positive astrocytes in ventral horn of SOD1 and SOD1 /mIgf-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156543 15657392 207677 20996 11179 SOD1 SOD1 SOD1 11 2.5 Immunofluorescence analysis identify GFAP positive astrocytes in ventral horn of SOD1 and SOD1 /mIgf-1 mIgf-1 mice at different ages A and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156544 15657392 207677 20996 11179 SOD1 SOD1 SOD1 11 2.5 Immunofluorescence analysis identify GFAP positive astrocytes in ventral horn of SOD1 and SOD1 /mIgf-1 mIgf-1 mice at different ages A and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156545 15657392 207677 20996 11179 SOD1 SOD1 SOD1 13 2.5 identify GFAP positive astrocytes in ventral horn of SOD1 and SOD1 /mIgf-1 mIgf-1 mice at different ages A and B 28 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156546 15657392 207678 8254 4235 GFAP GFAP GFAP 4 2.5 The intensity of the GFAP signal revealed progressive astrocytosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156547 15657392 207680 8254 4235 GFAP GFAP GFAP 7 2.5 Insert in D shows Western blot for GFAP in the spinal cord of SOD1 (lanes lanes 1 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156548 15657392 207680 20996 11179 SOD1 SOD1 SOD1 13 2.5 shows Western blot for GFAP in the spinal cord of SOD1 (lanes lanes 1 and 3 and SOD1 /mIgf-1 mIgf-1 (lanes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156549 15657392 207680 20996 11179 SOD1 SOD1 SOD1 19 2.5 spinal cord of SOD1 (lanes lanes 1 and 3 and SOD1 /mIgf-1 mIgf-1 (lanes lanes 2 and 4 mice at 28 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156550 15657392 207681 22551 11892 TNF TNF-alpha TNF-alpha 4 1.7 (c) c RT-PCR analysis of TNF-alpha and _amp_#223 -actin of wt (lane lane 1 MLC/mIgf-1 MLC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156551 15657392 207681 13966 29823 MYL6B MLC MLC 12 0.6 TNF-alpha and _amp_#223 -actin of wt (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156552 15657392 207681 20996 11179 SOD1 SOD1 SOD1 15 2.5 wt (lane lane 1 MLC/mIgf-1 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lane lane 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156553 15657392 207681 20996 11179 SOD1 SOD1 SOD1 19 2.5 MLC mIgf-1 (lane lane 2 SOD1 (lane lane 3 and SOD1 /mIgf-1 mIgf-1 (lane lane 4 transgenic mice at 123 d 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156554 15657392 207683 22551 11892 TNF TNF-alpha TNF-alpha 9 1.7 Lane 6 identifies the RNA positive control (pc) pc for TNF-alpha obtained from spleen 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156555 15657392 207684 20996 11179 SOD1 SOD1 SOD1 14 2.5 progression of the disease and prolongs the life span of SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156556 15657392 207685 20996 11179 SOD1 SOD1 SOD1 8 2.5 To evaluate the effects of mIgf-1 on the SOD1 neurodegenerative phenotype we compared double transgenic SOD1 and MLC/mIgf-1 MLC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156557 15657392 207685 20996 11179 SOD1 SOD1 SOD1 15 2.5 mIgf-1 on the SOD1 neurodegenerative phenotype we compared double transgenic SOD1 and MLC/mIgf-1 MLC mIgf-1 transgenic mice to their SOD1 littermates 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156558 15657392 207685 13966 29823 MYL6B MLC MLC 17 0.6 SOD1 neurodegenerative phenotype we compared double transgenic SOD1 and MLC/mIgf-1 MLC mIgf-1 transgenic mice to their SOD1 littermates 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156559 15657392 207685 20996 11179 SOD1 SOD1 SOD1 22 2.5 transgenic SOD1 and MLC/mIgf-1 MLC mIgf-1 transgenic mice to their SOD1 littermates 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156560 15657392 207686 20996 11179 SOD1 SOD SOD 1 2.2 The SOD and SOD1 x MLC/mIgf-1 MLC mIgf-1 (SOD1 SOD1 /mIgf-1) mIgf-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156561 15657392 207686 20996 11179 SOD1 SOD1 SOD1 3 2.5 The SOD and SOD1 x MLC/mIgf-1 MLC mIgf-1 (SOD1 SOD1 /mIgf-1) mIgf-1 transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156562 15657392 207686 13966 29823 MYL6B MLC MLC 5 0.6 The SOD and SOD1 x MLC/mIgf-1 MLC mIgf-1 (SOD1 SOD1 /mIgf-1) mIgf-1 transgenic mice were selected for 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156563 15657392 207686 20996 11179 SOD1 SOD1 SOD1 6 2.5 The SOD and SOD1 x MLC/mIgf-1 MLC mIgf-1 (SOD1 SOD1 /mIgf-1) mIgf-1 transgenic mice were selected for same expression level 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156564 15657392 207687 13966 29823 MYL6B MLC MLC 12 0.6 transgene was selectively expressed in skeletal muscle of both MLC/mIgf-1 MLC mIgf-1 and SOD1 /mIgf-1 mIgf-1 mice ( Fig 1 b 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156565 15657392 207687 20996 11179 SOD1 SOD1 SOD1 14 2.5 expressed in skeletal muscle of both MLC/mIgf-1 MLC mIgf-1 and SOD1 /mIgf-1 mIgf-1 mice ( Fig 1 b lanes 2 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156566 15657392 207687 20996 11179 SOD1 SOD SOD 49 2.2 b lanes 5-8 or in skeletal muscle of wild-type and SOD mice ( Fig 1 b lanes 1 and 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156567 15657392 207688 20996 11179 SOD1 SOD1 SOD1 13 2.5 1.8 d old disease onset was observed in the mutant SOD1 transgenic mice ( n = 30 Fig 1 c 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156568 15657392 207689 20996 11179 SOD1 SOD1 SOD1 2 2.5 Notably the SOD1 mice died within 10 d _amp_#177 0.6 of clinical disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156569 15657392 207690 20996 11179 SOD1 SOD1 SOD1 28 2.5 ( Fig 1 d of disease increasing the survival of SOD1 /mIgf-1 mIgf-1 mice ( n = 30 by ~30 d 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156570 15657392 207691 20996 11179 SOD1 SOD1 SOD1 2 2.5 Differences between SOD1 and SOD1 /mIgf-1 mIgf-1 were significantly relevant for onset ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156571 15657392 207691 20996 11179 SOD1 SOD1 SOD1 2 2.5 Differences between SOD1 and SOD1 /mIgf-1 mIgf-1 were significantly relevant for onset ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156572 15657392 207691 20996 11179 SOD1 SOD1 SOD1 4 2.5 Differences between SOD1 and SOD1 /mIgf-1 mIgf-1 were significantly relevant for onset ( LR = 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156573 15657392 207692 20996 11179 SOD1 SOD1 SOD1 10 2.5 mIgf-1 expression attenuates muscle atrophy increasing satellite cell activation in SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156574 15657392 207693 20996 11179 SOD1 SOD1 SOD1 0 2.5 SOD1 ( n = 7 and SOD1 /mIgf-1 mIgf-1 ( n 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156575 15657392 207693 20996 11179 SOD1 SOD1 SOD1 6 2.5 SOD1 ( n = 7 and SOD1 /mIgf-1 mIgf-1 ( n = 7 transgenic mice were analyzed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156576 15657392 207694 20996 11179 SOD1 SOD1 SOD1 7 2.5 At 123 d motor neuronal degeneration of SOD1 mice was accompanied by severe muscle atrophy ( Fig 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156577 15657392 207695 20996 11179 SOD1 SOD1 SOD1 6 2.5 In contrast at the same age SOD1 /mIgf-1 mIgf-1 transgenic mice did not show evident signs of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156578 15657392 207696 20996 11179 SOD1 SOD1 SOD1 7 2.5 Moreover muscle atrophy was substantially attenuated in SOD1 /mIgf-1 mIgf-1 offspring even after onset of denervation and paralysis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156579 15657392 207697 20996 11179 SOD1 SOD SOD 19 2.2 Pax-7 and desmin were increased to varying extents in affected SOD mice ( Fig 2 c whereas hallmarks of satellite cell 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156580 15657392 207697 14010 7612 MYOG MYOGENIN myogenin 46 1.0 nuclei ( Fig 2 a yellow arrows Pax-7 isoforms desmin myogenin and neonatal myosin heavy chain (MyHC) MyHC expression were present 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156581 15657392 207697 13956 23212 MYH14 myosin myosin 49 2.2 2 a yellow arrows Pax-7 isoforms desmin myogenin and neonatal myosin heavy chain (MyHC) MyHC expression were present exclusively in the 1 JUMiner_v2.2 1 0 0 2 7609 TotalCon:8<>23212|MYH14|79784|Complete__7599|MYO1E|4643|Complete__7600|MYO1F|4542|No_GeneRif__7603|MYO5B|4645|Complete__7604|MYO5C|55930|No_GeneRif__7605|MYO6|4646|Complete__7608|MYO9A|4649|No_GeneRif__7609|MYO9B|4650|Complete__<>AvaiableGeneRif=5<>BEST:7609|MYO9B|0.000676728031648133<>ScoreDetail__7599|MYO1E|0.000213289169928736__7609|MYO9B|0.000676728031648133__7603|MYO5B|0.000208463623097769__23212|MYH14|0.00012646793134598__7605|MYO6|0.000449401478939413__ 0 0 0 0 0 156582 15657392 207697 13948 7576 MYH6 MYHC MyHC 52 2.5 Pax-7 isoforms desmin myogenin and neonatal myosin heavy chain (MyHC) MyHC expression were present exclusively in the SOD1 /mIgf-1 mIgf-1 muscles 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156583 15657392 207697 20996 11179 SOD1 SOD1 SOD1 59 2.5 heavy chain (MyHC) MyHC expression were present exclusively in the SOD1 /mIgf-1 mIgf-1 muscles at all stages of disease including at 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156584 15657392 207697 16100 8621 PAX7 PAX7 Pax-7 9 0.0 In addition markers of satellite cell activity such as Pax-7 and desmin were increased to varying extents in affected SOD 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156585 15657392 207697 16100 8621 PAX7 PAX7 Pax-7 43 0.0 maturation including centralized nuclei ( Fig 2 a yellow arrows Pax-7 isoforms desmin myogenin and neonatal myosin heavy chain (MyHC) MyHC 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156586 15657392 207699 20996 11179 SOD1 SOD1 SOD1 14 2.5 2 d revealed that fiber type composition was altered in SOD1 soleus muscle even before overt disease (80 80 d with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156587 15657392 207700 20996 11179 SOD1 SOD1 SOD1 15 2.5 muscle fibers was maintained for a more extended period in SOD1 /mIgf-1 mIgf-1 mice which showed shifts in fiber composition only 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156588 15657392 207701 20996 11179 SOD1 SOD1 SOD1 15 2.5 there was not significant difference in fiber type composition between SOD1 and SOD1 /mIgf-1 mIgf-1 mice (not not depicted 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156589 15657392 207701 20996 11179 SOD1 SOD1 SOD1 15 2.5 there was not significant difference in fiber type composition between SOD1 and SOD1 /mIgf-1 mIgf-1 mice (not not depicted 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156590 15657392 207701 20996 11179 SOD1 SOD1 SOD1 17 2.5 not significant difference in fiber type composition between SOD1 and SOD1 /mIgf-1 mIgf-1 mice (not not depicted 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156591 15657392 207702 20996 11179 SOD1 SOD1 SOD1 6 2.5 The alteration in the heterogeneity of SOD1 muscle fibers indicate an alteration in motor neuron activity even 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156592 15657392 207702 20996 11179 SOD1 ALS ALS 31 2.2 support the hypothesis that delaying the progression and severity of ALS disease may depend on the maintenance of muscle integrity 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156593 15657392 207703 20996 11179 SOD1 SOD1 SOD1 17 2.5 e performed at different ages revealed that at 112 d SOD1 mice ( n = 7 showed symptom onset without evident 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156594 15657392 207704 20996 11179 SOD1 SOD1 SOD1 3 2.5 The condition of SOD1 mice rapidly deteriorated at 117 d as shown by the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156595 15657392 207705 20996 11179 SOD1 SOD1 SOD1 10 2.5 In contrast the pathological sign of disease were delayed in SOD1 /mIgf-1 mIgf-1 transgenic mice ( n = 7 as shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156596 15657392 207705 20996 11179 SOD1 SOD1 SOD1 39 2.5 _amp_#177 5.6 cm further when analyzed at same age as SOD1 mice and by their ability to move for a more 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156597 15657392 207706 20996 11179 SOD1 ALS ALS 28 2.2 an alternate therapeutic approach to counteract muscle wasting associated with ALS disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156598 15657392 207707 20996 11179 SOD1 SOD1 SOD1 7 2.5 An activated calcineurin isoform is induced in SOD1 /mIgf-1 mIgf-1 muscle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156599 15657392 207712 20996 11179 SOD1 SOD1 SOD1 12 2.5 low levels of CnA-_amp_#223 1 expression were not raised in SOD1 muscles ( Fig 3 a lane 3 Fig 3 b 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156600 15657392 207712 13966 29823 MYL6B MLC MLC 33 0.6 5 Fig 3 c or in uninjured wild-type and MLC/mIgf-1 MLC mIgf-1 muscle ( Fig 3 a and b lanes 1 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156601 15657392 207712 20996 11179 SOD1 SOD1 SOD1 46 2.5 ( Fig 3 a and b lanes 1 and 2 SOD1 /mIgf-1 mIgf-1 regenerating muscle dramatically increased CnA-_amp_#223 1 transcripts (73 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156602 15657392 207714 20996 11179 SOD1 SOD1 SOD1 5 2.5 Preservation of neuromuscular junctions in SOD1 /mIgf-1 mIgf-1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156603 15657392 207715 20996 11179 SOD1 SOD1 SOD1 21 2.5 neuron diseases also affect the configuration of neuromuscular junctions in SOD1 mice characterized by the diffusion of acetylcholine receptor (AChR) AChR 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156604 15657392 207716 20996 11179 SOD1 SOD1 SOD1 3 2.5 At 123 d SOD1 paralyzed muscle showed 56 _amp_#177 0.2% of diffuse AChR expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156605 15657392 207716 20996 11179 SOD1 SOD1 SOD1 28 2.5 ( Fig 4 a were preserved in muscles of age-matched SOD1 /mIgf-1 mIgf-1 mice which showed only 3.3 _amp_#177 0.4% of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156606 15657392 207717 20996 11179 SOD1 SOD1 SOD1 4 2.5 At comparable end-stage disease SOD1 /mIgf-1 mIgf-1 muscle displayed only 18 _amp_#177 0.4% of diffuse 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156607 15657392 207718 20996 11179 SOD1 SOD1 SOD1 17 2.5 analysis ( Fig 4 b high AChR expression levels in SOD1 muscle were reduced in SOD1 /mIgf-1 mIgf-1 mice at all 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156608 15657392 207718 20996 11179 SOD1 SOD1 SOD1 22 2.5 high AChR expression levels in SOD1 muscle were reduced in SOD1 /mIgf-1 mIgf-1 mice at all stages observed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156609 15657392 207719 20996 11179 SOD1 SOD1 SOD1 12 2.5 ( n = 6 revealed that AChR mRNA expression in SOD1 paralyzed muscle (123 123 d was 68 _amp_#177 2.4% higher 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156610 15657392 207719 20996 11179 SOD1 SOD1 SOD1 28 2.5 68 _amp_#177 2.4% higher than that observed in age matched SOD1 /mIgf-1 mIgf-1 mice whereas the increase in mRNA expression in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156611 15657392 207719 20996 11179 SOD1 SOD1 SOD1 38 2.5 /mIgf-1 mIgf-1 mice whereas the increase in mRNA expression in SOD1 mice was of 32 _amp_#177 1.9% when SOD1 and SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156612 15657392 207719 20996 11179 SOD1 SOD1 SOD1 46 2.5 expression in SOD1 mice was of 32 _amp_#177 1.9% when SOD1 and SOD1 /mIgf-1 mIgf-1 mice where analyzed at comparable end-stage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156613 15657392 207719 20996 11179 SOD1 SOD1 SOD1 46 2.5 expression in SOD1 mice was of 32 _amp_#177 1.9% when SOD1 and SOD1 /mIgf-1 mIgf-1 mice where analyzed at comparable end-stage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156614 15657392 207719 20996 11179 SOD1 SOD1 SOD1 48 2.5 SOD1 mice was of 32 _amp_#177 1.9% when SOD1 and SOD1 /mIgf-1 mIgf-1 mice where analyzed at comparable end-stage disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156615 15657392 207721 449 329 AGRN AGRIN agrin 13 1.0 AChR clusters at the end plate requires the expression of agrin a large proteoglycan in the synaptic cleft that plays an 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156616 15657392 207722 449 329 AGRN AGRIN Agrin 0 1.0 Agrin expression was significantly down-regulated in paralyzed SOD1 compared with SOD 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156617 15657392 207722 20996 11179 SOD1 SOD1 SOD1 7 2.5 Agrin expression was significantly down-regulated in paralyzed SOD1 compared with SOD /mIgf-1 mIgf-1 muscle ( Fig 4 c 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156618 15657392 207722 20996 11179 SOD1 SOD SOD 10 2.2 Agrin expression was significantly down-regulated in paralyzed SOD1 compared with SOD /mIgf-1 mIgf-1 muscle ( Fig 4 c analyzed at comparable 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156619 15657392 207723 20996 11179 SOD1 SOD1 SOD1 7 2.5 Muscle-restricted mIgf-1 prolongs motor neuronal function in SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156620 15657392 207724 20996 11179 SOD1 SOD1 SOD1 9 2.5 Histological analysis of the ventral spinal cord revealed that SOD1 mice ( n = 7 presented a progressive reduction in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156621 15657392 207725 20996 11179 SOD1 SOD1 SOD1 1 2.5 Specifically SOD1 mice showed a reduction of 37 and 55% in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156622 15657392 207726 20996 11179 SOD1 SOD1 SOD1 9 2.5 In contrast mIgf-1 expression induced motor neuron survival in SOD1 /mIgf-1 mIgf-1 mice ( n = 7 at all ages 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156623 15657392 207726 20996 11179 SOD1 ALS ALS 47 2.2 mIgf-1 expression preserves the motor neuron during the progression of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156624 15657392 207727 20996 11179 SOD1 ALS ALS 10 2.2 One of the prominent markers of motor neuron dysfunction in ALS mice is the activation of astrocytes leading to motor weakness 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156625 15657392 207728 8254 4235 GFAP GFAP GFAP 7 2.5 Comparable patterns of glial fibrillary acidic protein (GFAP) GFAP immunoreactivity were found in spinal cords of SOD1 ( n 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156626 15657392 207728 20996 11179 SOD1 SOD1 SOD1 15 2.5 protein (GFAP) GFAP immunoreactivity were found in spinal cords of SOD1 ( n = 6 and SOD /mIgf-1 mIgf-1 ( n 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156627 15657392 207728 20996 11179 SOD1 SOD SOD 21 2.2 in spinal cords of SOD1 ( n = 6 and SOD /mIgf-1 mIgf-1 ( n = 6 transgenic mice before the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156628 15657392 207729 20996 11179 SOD1 SOD1 SOD1 10 2.5 at paralysis stage (123 123 d the spinal cord of SOD1 mice demonstrated a marked increase in astroglial activation ( Fig 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156629 15657392 207729 8254 4235 GFAP GFAP GFAP 28 2.5 activation ( Fig 5 b C with an increase in GFAP expression of ~55 _amp_#177 0.2% ( Fig 5 b D 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156630 15657392 207729 8254 4235 GFAP GFAP GFAP 45 2.5 Fig 5 b D insert lane 3 compared with the GFAP expression levels displayed in the spinal cord of age matched 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156631 15657392 207729 20996 11179 SOD1 SOD1 SOD1 56 2.5 expression levels displayed in the spinal cord of age matched SOD1 /mIgf-1 mIgf-1 transgenic mice ( Fig 5 b D and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156632 15657392 207730 8254 4235 GFAP GFAP GFAP 10 2.5 At comparable end-stage disease there were no significant differences in GFAP expression between SOD1 and SOD1 /mIgf-1 mIgf-1 mice although SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156633 15657392 207730 20996 11179 SOD1 SOD1 SOD1 13 2.5 disease there were no significant differences in GFAP expression between SOD1 and SOD1 /mIgf-1 mIgf-1 mice although SOD1 mice continued to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156634 15657392 207730 20996 11179 SOD1 SOD1 SOD1 13 2.5 disease there were no significant differences in GFAP expression between SOD1 and SOD1 /mIgf-1 mIgf-1 mice although SOD1 mice continued to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156635 15657392 207730 20996 11179 SOD1 SOD1 SOD1 15 2.5 were no significant differences in GFAP expression between SOD1 and SOD1 /mIgf-1 mIgf-1 mice although SOD1 mice continued to express 13% 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156636 15657392 207730 20996 11179 SOD1 SOD1 SOD1 19 2.5 GFAP expression between SOD1 and SOD1 /mIgf-1 mIgf-1 mice although SOD1 mice continued to express 13% more GFAP as compared with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156637 15657392 207730 8254 4235 GFAP GFAP GFAP 26 2.5 mIgf-1 mice although SOD1 mice continued to express 13% more GFAP as compared with SOD1 /mIgf-1 mIgf-1 mice (unpublished unpublished data 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156638 15657392 207730 20996 11179 SOD1 SOD1 SOD1 30 2.5 mice continued to express 13% more GFAP as compared with SOD1 /mIgf-1 mIgf-1 mice (unpublished unpublished data 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156639 15657392 207731 22551 11892 TNF TNF-alpha TNF-alpha 15 1.7 be correlated with the expression of certain cytokines such as TNF-alpha which enhance the response to inflammatory states and contribute to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156640 15657392 207731 20996 11179 SOD1 SOD1 SOD1 33 2.5 states and contribute to the progression of neurological dysfunction in SOD1 mice ( Elliott 2001 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156641 15657392 207732 22551 11892 TNF TNF-alpha TNF-alpha 1 1.7 Although TNF-alpha expression was normally undetectable in the CNS of healthy mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156642 15657392 207732 20996 11179 SOD1 SOD1 SOD1 28 2.5 1 and 2 it accumulated in the spinal cord of SOD1 mice at paralysis stage (123 123 d Fig 5 c 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156643 15657392 207733 22551 11892 TNF TNF-alpha TNF-alpha 2 1.7 In contrast TNF-alpha expression was not apparent in the spinal cord of SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156644 15657392 207733 20996 11179 SOD1 SOD1 SOD1 13 2.5 TNF-alpha expression was not apparent in the spinal cord of SOD1 /mIgf-1 mIgf-1 transgenic mice ( Fig 5 c lane 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156645 15657392 207733 20996 11179 SOD1 ALS ALS 47 2.2 astrocytosis and inflammatory cytokines that normally exacerbate the pathogenesis of ALS disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156646 15657392 207734 20996 11179 SOD1 ALS ALS 0 2.2 ALS is emerging as a multi-systemic disease in which the alteration 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156647 15657392 207736 20996 11179 SOD1 SOD1 SOD1 14 2.5 determined whether the dramatic prolongation of CNS tissue integrity in SOD1 /mIgf-1 mIgf-1 mice derives from the direct retrograde transport of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156648 15657392 207736 9939 5464 IGF1 IGF1 Igf-1 35 3.5 mIgf-1 or indirect action either through distal activation of endogenous Igf-1 expression or through other trophic factors secreted by SOD /mIgf-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156649 15657392 207736 20996 11179 SOD1 SOD SOD 44 2.2 endogenous Igf-1 expression or through other trophic factors secreted by SOD /mIgf-1 mIgf-1 muscle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156650 15657392 207739 9939 5464 IGF1 IGF1 Igf-1 1 3.5 The Igf-1 cDNA used by Kaspar et al 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156651 15657392 207742 9939 5464 IGF1 IGF1 Igf-1 3 3.5 The importance of Igf-1 isoform choice in designing therapeutic strategies cannot be overstressed because 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156652 15657392 207743 20996 11179 SOD1 ALS ALS 37 2.2 counteract the degeneration of both muscle and motor neuron in ALS disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00171098438242487<>ScoreDetail__5468|IGFALS|0.000488478876777714__11179|SOD1|0.00171098438242487__ 0 0 0 0 0 156653 15657392 207745 20996 11179 SOD1 SOD SOD 0 2.2 SOD transgenic mice (Jackson Jackson Laboratory express a transgenic human mutant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156654 15657392 207745 20996 11179 SOD1 SOD1 SOD1 10 2.5 transgenic mice (Jackson Jackson Laboratory express a transgenic human mutant SOD1 allele containing the Gly93 Ala (G93A) G93A substitution driven by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156655 15657392 207746 20996 11179 SOD1 SOD1 SOD1 1 2.5 The SOD1 B6J mice were crossed with MLC/mIgf-1 MLC mIgf-1 FVB mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156656 15657392 207746 13966 29823 MYL6B MLC MLC 7 0.6 The SOD1 B6J mice were crossed with MLC/mIgf-1 MLC mIgf-1 FVB mice ( Musar_amp_ograve et al. 2001 for seven 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156657 15657392 207746 20996 11179 SOD1 SOD1 SOD1 22 2.5 Musar_amp_ograve et al. 2001 for seven different generations to obtain SOD1 /mIgf-1 mIgf-1 B6J inbred transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156658 15657392 207755 13948 7576 MYH6 MYHC MyHC 38 2.5 RT and incubated overnight at 4degreeC with primary antibodies neonatal MyHC (neo-MyHC), neo-MyHC MyHC-fast Alexa Fluor 488-conjugated alpha-bungarotoxin CnA-_amp_#223 1 (from 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156659 15657392 207755 8254 4235 GFAP GFAP GFAP 55 2.5 (from from C Klee National Institutes of Health Bethesda MD GFAP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156660 15657392 207760 1759 1102 BRD1 BRL BRL 8 0.3 RNA was extracted from muscles by RNA-TRIzol-kit (GIBCO GIBCO BRL 1 JUMiner_v2.2 1 2 gibco brl 0 0 0 0 0 0 0 0 156661 15657392 207763 13966 29823 MYL6B MLC MLC 8 0.6 RNA was isolated from spinal cord of wild-type MLC/mIgf-1, MLC mIgf-1 and SOD and SOD1 /mIgf-1 mIgf-1 transgenic mice 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 156662 15657392 207763 20996 11179 SOD1 SOD SOD 10 2.2 isolated from spinal cord of wild-type MLC/mIgf-1, MLC mIgf-1 and SOD and SOD1 /mIgf-1 mIgf-1 transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156663 15657392 207763 20996 11179 SOD1 SOD1 SOD1 12 2.5 spinal cord of wild-type MLC/mIgf-1, MLC mIgf-1 and SOD and SOD1 /mIgf-1 mIgf-1 transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156664 15657392 207764 22551 11892 TNF TNF-alpha TNF-alpha 5 1.7 The following oligonucleotides were used TNF-alpha sense 5'-CCCAGACCCTCACACACTCAGAT-3' and anti-sense 5'-TTGTCCCTTGAAGAGAACCTG-3' _amp_#223 -actin sense 5'-GTGGGCCGCTCTAGGCACAA-3' and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156665 15657392 207767 19573 10691 SDS SDS SDS 11 0.0 amounts of protein from each muscle lysate were separated in SDS polyacrylamide gel and transferred onto a hybond C extra nitrocellulose 1 JUMiner_v2.2 1 0 0 2 19440 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:19440|SBDS|0.000407140221636958<>ScoreDetail__10691|SDS|0.000301114122252334__19440|SBDS|0.000407140221636958__ 0 0 0 0 0 156666 15657392 207768 20996 11179 SOD1 SOD hSOD 6 2.2 Filters were blotted with antibodies against hSOD Pax7 myogenin desmin neo-MyHC (from from S Schiaffino University of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156667 15657392 207768 16100 8621 PAX7 PAX7 Pax7 7 0.5 Filters were blotted with antibodies against hSOD Pax7 myogenin desmin neo-MyHC (from from S Schiaffino University of Padova 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156668 15657392 207768 14010 7612 MYOG MYOGENIN myogenin 8 1.0 Filters were blotted with antibodies against hSOD Pax7 myogenin desmin neo-MyHC (from from S Schiaffino University of Padova Padova 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156669 15657392 207768 449 329 AGRN AGRIN Agrin 19 1.0 neo-MyHC (from from S Schiaffino University of Padova Padova Italy Agrin GFAP 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156670 15657392 207768 8254 4235 GFAP GFAP GFAP 20 2.5 (from from S Schiaffino University of Padova Padova Italy Agrin GFAP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156671 15657392 207769 9939 5464 IGF1 IGF1 Igf-1 3 3.5 Organization of the Igf-1 gene 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156672 15657392 207770 9939 5464 IGF1 IGF1 Igf-1 4 3.5 As its name implies Igf-1 is similar to insulin in structure 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156673 15657392 207771 9939 5464 IGF1 IGF1 Igf-1 2 3.5 The mature Igf-1 is a single-chain protein of 70 aa and differs from 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156674 15657392 207772 9939 5464 IGF1 IGF1 Igf-1 2 3.5 The rodent Igf-1 gene contains six exons separated by five introns (Fig Fig 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156675 15657392 207775 9939 5464 IGF1 IGF1 Igf-1 24 3.5 to all isoforms as well as part of the mature Igf-1 peptide 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 156676 15657392 207776 9939 5464 IGF1 IGF1 Igf-1 27 3.5 region of the E-peptide which is also common to all Igf-1 mRNAs 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157135 15668976 208352 9947 5468 IGFALS ALS ALS 8 0.3 The causative pathomechanism of sporadic amyotrophic lateral sclerosis (ALS) ALS is not clearly understood 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00125566384543045<>ScoreDetail__5468|IGFALS|0.00103406326034063__11179|SOD1|0.00125566384543045__ 0 0 0 0 0 157136 15668976 208353 9947 5468 IGFALS ALS ALS 21 0.3 degenerating spinal motor neurons isolated from autopsied patients with sporadic ALS were examined 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00125566384543045<>ScoreDetail__5468|IGFALS|0.00103406326034063__11179|SOD1|0.00125566384543045__ 0 0 0 0 0 157137 15668976 208357 6452 3240 EGR3 EGR3 EGR3 23 2.5 as dynactin microtubule-associated proteins and early growth response 3 (EGR3) EGR3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157138 15668976 208359 14352 7794 NFKB1 NF-kappaB NF-kappaB 26 0.0 -9 were upregulated whereas cell death inhibitors acetyl-CoA transporter and NF-kappaB were also upregulated 1 JUMiner_v2.2 1 1 nf-kappab; 0 0 0 0 0 0 0 0 157139 15668976 208360 4649 2169 CNTF CNTF CNTF 9 1.9 Moreover neuroprotective neurotrophic factors such as ciliary neurotrophic factor (CNTF), CNTF Hepatocyte growth factor (HGF), HGF and glial cell line-derived neurotrophic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157140 15668976 208360 9207 4893 HGF HGF HGF 13 1.2 as ciliary neurotrophic factor (CNTF), CNTF Hepatocyte growth factor (HGF), HGF and glial cell line-derived neurotrophic factor were upregulated 1 JUMiner_v2.2 1 0 0 2 4893 TotalCon:3<>4893|HGF|3082|Complete__6018|IL6|3569|Complete__11187|SOS1|6654|Complete__<>AvaiableGeneRif=3<>BEST:4893|HGF|0.00120521080592291<>ScoreDetail__4893|HGF|0.00120521080592291__11187|SOS1|0.000364823348694316__6018|IL6|0.00057724366151626__ 0 0 0 0 0 157141 15668976 208362 9947 5468 IGFALS ALS ALS 8 0.3 The motor neuron-specific gene expression profile in sporadic ALS can provide direct information on the genes leading to neurodegeneration 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00125566384543045<>ScoreDetail__5468|IGFALS|0.00103406326034063__11179|SOD1|0.00125566384543045__ 0 0 0 0 0 157368 15681814 208634 22671 11998 TP53 p53 p53 9 1.4 New therapeutic strategies and drug candidates for neurodegenerative diseases p53 and TNF-alpha inhibitors and GLP-1 receptor agonists 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157369 15681814 208634 22551 11892 TNF TNF-alpha TNF-alpha 11 2.7 therapeutic strategies and drug candidates for neurodegenerative diseases p53 and TNF-alpha inhibitors and GLP-1 receptor agonists 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157370 15681814 208634 8198 4191 GCG GLP1 GLP-1 14 1.0 drug candidates for neurodegenerative diseases p53 and TNF-alpha inhibitors and GLP-1 receptor agonists 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157371 15681814 208640 22551 11892 TNF TNF-alpha TNF-alpha 3 2.7 Such targets include TNF-alpha p53 and GLP-1 receptor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157372 15681814 208640 22671 11998 TP53 p53 p53 4 1.4 Such targets include TNF-alpha p53 and GLP-1 receptor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157373 15681814 208640 8198 4191 GCG GLP1 GLP-1 6 1.0 Such targets include TNF-alpha p53 and GLP-1 receptor 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157374 15681814 208641 22551 11892 TNF TNF-alpha TNF-alpha 2 2.7 The cytokine TNF-alpha is elevated in Alzheimer's disease Parkinson's disease stroke and amyotrophic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157375 15681814 208643 22671 11998 TP53 p53 p53 6 1.4 The intracellular protein and transcription factor p53 is activated by the Alzheimer's disease toxic peptide Abeta as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157376 15681814 208643 926 620 APP ABETA Abeta 15 1.0 factor p53 is activated by the Alzheimer's disease toxic peptide Abeta as well as by excess glutamate and hypoxia to trigger 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157377 15681814 208645 8406 4324 GLP1R GLP1R GLP-1R 6 0.9 Stimulation of the glucagon-like peptide-1 receptor (GLP-1R) GLP-1R in brain is associated with neurotrophic functions that additionally can 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157731 15691215 209294 20996 11179 SOD1 ALS ALS 3 1.4 Amyotrophic lateral sclerosis (ALS) ALS is a progressive neurodegenerative disease for which no cure or 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00128599243576359<>ScoreDetail__5468|IGFALS|0.000890990713135259__11179|SOD1|0.00128599243576359__ 0 0 0 0 0 157732 15691215 209296 20996 11179 SOD1 ALS ALS 7 1.4 The discovery that a small percentage of ALS cases are familial and involve mutation in a superoxide dismutase 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00128599243576359<>ScoreDetail__5468|IGFALS|0.000890990713135259__11179|SOD1|0.00128599243576359__ 0 0 0 0 0 157733 15691215 209296 20996 11179 SOD1 SOD1 SOD1 19 1.4 familial and involve mutation in a superoxide dismutase gene (SOD1) SOD1 led to the development of transgenic mouse models presently widely 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157734 15691215 209297 23910 12680 VEGFA VEGF VEGF 8 4.1 Mutations in the vascular endothelial growth factor gene (VEGF) VEGF also appear to be involved 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157735 15691215 209300 23910 12680 VEGFA VEGF VEGF 3 4.1 Gene transfer of VEGF or glial cell-line derived neurotrophic factor anti-inflammatory COX-2 inhibitors and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 157736 15691215 209300 17610 9605 PTGS2 COX-2 COX-2 11 1.0 transfer of VEGF or glial cell-line derived neurotrophic factor anti-inflammatory COX-2 inhibitors and minocycline have had particularly promising results in mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 150946 15777251 199027 20996 11179 SOD1 ALS ALS 21 0.0 PD Alzheimer's disease (AD) AD or amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000720315629212073<>ScoreDetail__5468|IGFALS|0.000377165930823331__11179|SOD1|0.000720315629212073__ 0 0 0 0 0 150947 15777251 199034 9905 5438 IFNG IFN-gamma IFN-gamma 17 0.8 experimental autoimmune encephalomyelitis (EAE) EAE display gender specific alterations of IFN-gamma and IL-12 variations of TNF and IL-6 were associated with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 150948 15777251 199034 10463 6018 IL6 IL-6 IL-6 24 1.5 specific alterations of IFN-gamma and IL-12 variations of TNF and IL-6 were associated with PD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 150949 15777251 199034 22551 11892 TNF TNF TNF 22 0.1 display gender specific alterations of IFN-gamma and IL-12 variations of TNF and IL-6 were associated with PD 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 150950 15777251 199035 10463 6018 IL6 IL-6 IL-6 14 1.5 more acute neurodegenerative conditions such as stroke the effect of IL-6 gene G-174C polymorphism was different in males and females 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 150961 15782606 199052 20996 11179 SOD1 ALS ALS 9 0.0 Primary progressive multiple sclerosis as a differential diagnosis of ALS a case report 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000465747863617697<>ScoreDetail__5468|IGFALS|0.000403027181944382__11179|SOD1|0.000465747863617697__ 0 0 0 0 0 150962 15782606 199056 20996 11179 SOD1 ALS ALS 15 0.0 and decreased number of motor units in the extremities suggesting ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000465747863617697<>ScoreDetail__5468|IGFALS|0.000403027181944382__11179|SOD1|0.000465747863617697__ 0 0 0 0 0 150963 15782606 199057 20527 30646 SND1 P100 P100 20 1.0 prolonged central conduction time of MEP and SEP a delayed P100 latency of VEP and a increased IgG index in the 1 JUMiner_v2.2 1 0 0 2 2557 TotalCon:4<>30646|SND1|27044|Complete__1249|TPX2|22974|Complete__2557|CUX1|1523|Complete__8088|OAS3|4940|Complete__<>AvaiableGeneRif=4<>BEST:2557|CUX1|0.0002743278966532<>ScoreDetail__1249|TPX2|0.000153374233128834__8088|OAS3|0__30646|SND1|0.00027266530334015__2557|CUX1|0.0002743278966532__ 0 0 0 0 0 150964 15782606 199057 5142 2537 CTSL1 MEP MEP 15 0.0 head and spinal MRI a prolonged central conduction time of MEP and SEP a delayed P100 latency of VEP and a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 150965 15782606 199057 13321 14668 MMEL1 SEP SEP 17 0.0 spinal MRI a prolonged central conduction time of MEP and SEP a delayed P100 latency of VEP and a increased IgG 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>14668|MMEL1|79258|No_GeneRif__9103|PLXNB1|5364|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 150966 15782606 199057 11629 6493 LAMC2 CSF CSF 31 0.0 latency of VEP and a increased IgG index in the CSF indicated primary progressive type multiple sclerosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 150967 15782606 199059 20996 11179 SOD1 ALS ALS-like 22 0.0 the anterior horn cells/intramedullary cells intramedullary ventral roots explained the ALS-like clinical picture 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000465747863617697<>ScoreDetail__5468|IGFALS|0.000403027181944382__11179|SOD1|0.000465747863617697__ 0 0 0 0 0 151001 15799549 199163 20996 11179 SOD1 ALS ALS 14 0.0 markers in affected neural tissues of amyotrophic lateral sclerosis (ALS) ALS patients 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000936474939593148<>ScoreDetail__5468|IGFALS|0.00019208605455244__11179|SOD1|0.000936474939593148__ 0 0 0 0 0 151002 15799549 199164 20996 11179 SOD1 ALS ALS 10 0.0 We examined immunocytochemically spinal cord tissues of six patients with ALS two with corticospinal tract degeneration secondary to cerebral infarcts and 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000936474939593148<>ScoreDetail__5468|IGFALS|0.00019208605455244__11179|SOD1|0.000936474939593148__ 0 0 0 0 0 151003 15799549 199165 20996 11179 SOD1 ALS ALS 0 0.0 ALS spinal cords had dense macrophage infiltration (one one log greater 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000936474939593148<>ScoreDetail__5468|IGFALS|0.00019208605455244__11179|SOD1|0.000936474939593148__ 0 0 0 0 0 151004 15799549 199166 17610 9605 PTGS2 COX-2 COX-2 10 1.8 in ALS spinal cord showed strong expression of cyclooxygenase-2 (COX-2) COX-2 (one one log greater than control tissues and inducible nitric 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 151005 15799549 199166 20996 11179 SOD1 ALS ALS 2 0.0 Macrophages in ALS spinal cord showed strong expression of cyclooxygenase-2 (COX-2) COX-2 (one 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000936474939593148<>ScoreDetail__5468|IGFALS|0.00019208605455244__11179|SOD1|0.000936474939593148__ 0 0 0 0 0 151006 15799549 199168 22190 11827 TJP1 ZO-1 ZO-1 8 4.0 Vessels showed damage to the tight junction protein ZO-1 in relation to perivascular CD40 receptor-positive macrophages and CD40 ligand-positive 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 151007 15799549 199168 3889 11919 CD40 CD40 CD40 13 0.3 to the tight junction protein ZO-1 in relation to perivascular CD40 receptor-positive macrophages and CD40 ligand-positive T lymphocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 151008 15799549 199168 3889 11919 CD40 CD40 CD40 17 0.3 protein ZO-1 in relation to perivascular CD40 receptor-positive macrophages and CD40 ligand-positive T lymphocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 151009 15799549 199169 20996 11179 SOD1 ALS ALS 0 0.0 ALS spinal cords but not control cords were sparsely infiltrated with 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000936474939593148<>ScoreDetail__5468|IGFALS|0.00019208605455244__11179|SOD1|0.000936474939593148__ 0 0 0 0 0 151010 15799549 199170 17610 9605 PTGS2 COX COX-2-negative 18 0.0 hemispheric cerebral infarction macrophage infiltration of the white matter was COX-2-negative and restricted to lateral and anterior corticospinal tracts 11 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 151011 15799549 199171 20996 11179 SOD1 ALS ALS 6 0.0 Our data suggest that inflammation in ALS spinal cord and cortex is based on innate immune responses 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000936474939593148<>ScoreDetail__5468|IGFALS|0.00019208605455244__11179|SOD1|0.000936474939593148__ 0 0 0 0 0 151248 15804265 199551 20996 11179 SOD1 ALS ALS 11 1.7 of intraperitoneal injection of Rofecoxib in a mouse model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00103560857600355<>ScoreDetail__5468|IGFALS|0.00059183270862103__11179|SOD1|0.00103560857600355__ 0 0 0 0 0 151249 15804265 199552 20996 11179 SOD1 ALS ALS 16 1.7 are involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00103560857600355<>ScoreDetail__5468|IGFALS|0.00059183270862103__11179|SOD1|0.00103560857600355__ 0 0 0 0 0 151250 15804265 199553 17610 9605 PTGS2 COX-2 COX-2 9 1.0 Inhibition of a key mediator of inflammation cyclooxygenase 2 (COX-2), COX-2 represents a promising therapeutic approach in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 151251 15804265 199553 20996 11179 SOD1 ALS ALS 16 1.7 cyclooxygenase 2 (COX-2), COX-2 represents a promising therapeutic approach in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00103560857600355<>ScoreDetail__5468|IGFALS|0.00059183270862103__11179|SOD1|0.00103560857600355__ 0 0 0 0 0 151252 15804265 199554 17610 9605 PTGS2 COX-2 COX-2 10 1.0 Here we tested the in vivo effects of a specific COX-2 inhibitor Rofecoxib administered by intraperitoneal injection in the SOD1(G93A SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 151253 15804265 199554 20996 11179 SOD1 SOD1 SOD1 19 1.7 COX-2 inhibitor Rofecoxib administered by intraperitoneal injection in the SOD1(G93A SOD1 G93A G1H mouse model of the familial form of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 151254 15804265 199554 20996 11179 SOD1 ALS ALS 28 1.7 SOD1 G93A G1H mouse model of the familial form of ALS (fALS) fALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00103560857600355<>ScoreDetail__5468|IGFALS|0.00059183270862103__11179|SOD1|0.00103560857600355__ 0 0 0 0 0 151255 15804265 199555 21239 11280 SQSTM1 P60 P60 7 0.0 Rofecoxib administration commenced at postnatal day 60 (P60), P60 since the hallmarks of inflammation in the spinal cord were 1 JUMiner_v2.2 1 0 0 2 11916 TotalCon:4<>11280|SQSTM1|8878|Complete__11916|TNFRSF1A|7132|Complete__13209|ARHGEF5|7984|Complete__11387|STIP1|10963|Complete__<>AvaiableGeneRif=4<>BEST:11916|TNFRSF1A|0.00038587446428289<>ScoreDetail__11916|TNFRSF1A|0.00038587446428289__11387|STIP1|0__13209|ARHGEF5|0__11280|SQSTM1|0.000321300321300321__ 0 0 0 0 0 153856 15846792 203807 20996 11179 SOD1 ALS ALS 19 0.0 microglia in an adult-onset neurodegenerative disease amyotrophic lateral sclerosis (ALS), ALS and pays particular attention to the possible mechanisms of initiation 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00104727707959306<>ScoreDetail__5468|IGFALS|0.00032441200324412__11179|SOD1|0.00104727707959306__ 0 0 0 0 0 153857 15846792 203809 20996 11179 SOD1 ALS ALS 10 0.0 The neuroinflammatory changes that occur in a mouse model of ALS are summarized 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00104727707959306<>ScoreDetail__5468|IGFALS|0.00032441200324412__11179|SOD1|0.00104727707959306__ 0 0 0 0 0 147157 15962273 193995 20996 11179 SOD1 ALS ALS 13 0.0 microglia in the spinal cord of amyotrophic lateral sclerosis (ALS) ALS patients is usually accompanied by inflammatory biochemical changes but these 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000879667751065275<>ScoreDetail__5468|IGFALS|0.000768344218209758__11179|SOD1|0.000879667751065275__ 0 0 0 0 0 147158 15962273 193996 3758 10618 CCL2 MCP-1 MCP-1 3 2.8 Monocyte chemoattractant protein-1 (MCP-1) MCP-1 is critical for recruitment of inflammatory cells of monocytic lineage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 147159 15962273 193997 3758 10618 CCL2 MCP-1 MCP-1 0 2.8 MCP-1 concentrations were measured by an enzyme-linked immunosorbent assay in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 147160 15962273 193997 11629 6493 LAMC2 CSF CSF 13 0.0 by an enzyme-linked immunosorbent assay in the cerebrospinal fluid (CSF) CSF and the serum of 27 patients with ALS and 30 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 147161 15962273 193997 20996 11179 SOD1 ALS ALS 21 0.0 fluid (CSF) CSF and the serum of 27 patients with ALS and 30 patients with noninflammatory neurological diseases 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000879667751065275<>ScoreDetail__5468|IGFALS|0.000768344218209758__11179|SOD1|0.000879667751065275__ 0 0 0 0 0 147162 15962273 193998 3758 10618 CCL2 MCP-1 MCP-1 3 2.8 In ALS circulating MCP-1 levels were significantly increased in the serum and particularly in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 147163 15962273 193998 20996 11179 SOD1 ALS ALS 1 0.1 In ALS circulating MCP-1 levels were significantly increased in the serum and 6 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000879667751065275<>ScoreDetail__5468|IGFALS|0.000768344218209758__11179|SOD1|0.000879667751065275__ 0 0 0 0 0 147164 15962273 193998 11629 6493 LAMC2 CSF CSF 15 0.0 were significantly increased in the serum and particularly in the CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 147165 15962273 193999 3758 10618 CCL2 MCP-1 MCP-1 2 2.8 Immunoreactivity for MCP-1 in ALS spinal cord was detected mostly in astrocytes but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 147166 15962273 193999 20996 11179 SOD1 ALS ALS 4 0.1 Immunoreactivity for MCP-1 in ALS spinal cord was detected mostly in astrocytes but also in 6 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000879667751065275<>ScoreDetail__5468|IGFALS|0.000768344218209758__11179|SOD1|0.000879667751065275__ 0 0 0 0 0 147167 15962273 194000 3758 10618 CCL2 MCP-1 MCP-1 6 2.8 Our findings suggest a role for MCP-1 as an important molecular mediator of the injury response in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 147168 15962273 194000 20996 11179 SOD1 ALS ALS 17 0.0 as an important molecular mediator of the injury response in ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000879667751065275<>ScoreDetail__5468|IGFALS|0.000768344218209758__11179|SOD1|0.000879667751065275__ 0 0 0 0 0 147249 15974901 194280 17610 9605 PTGS2 COX COX 10 0.0 are reports suggesting that NSAIDs act independently of cyclooxygenase (COX) COX inhibition but only at higher doses 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 135199 16014720 179141 13419 7218 MPO MPO MPO 5 7.1 Here we show that myeloperoxidase (MPO), MPO a key oxidant-producing enzyme during inflammation is upregulated in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135200 16014720 179142 13419 7218 MPO MPO MPO 13 7.1 that ventral midbrain dopaminergic neurons of mutant mice deficient in MPO are more resistant to MPTP-induced cytotoxicity than their wild-type littermates 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135201 16014720 179143 13419 7218 MPO MPO MPO 6 7.1 Supporting the oxidative damaging role of MPO in this PD model are the demonstrations that MPO-specific biomarkers 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135202 16014720 179143 13419 7218 MPO MPO MPO-specific 15 1.0 of MPO in this PD model are the demonstrations that MPO-specific biomarkers 3-chlorotyrosine and hypochlorous acid-modified proteins increase in the brains 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135203 16014720 179144 13419 7218 MPO MPO MPO 4 7.1 This study demonstrates that MPO participates in the MPTP neurotoxic process and suggests that inhibitors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135204 16014720 179144 13419 7218 MPO MPO MPO 16 7.1 in the MPTP neurotoxic process and suggests that inhibitors of MPO may provide a protective benefit in PD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135205 16014720 179150 14535 7873 NOS2A iNOS iNOS 9 2.2 For instance NADPH oxidase and inducible nitric oxide synthase (iNOS), iNOS which are major sources of inflammatory oxidants are upregulated in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135206 16014720 179151 14535 7873 NOS2A iNOS iNOS 8 2.2 Studies of mice deficient in NADPH oxidase or iNOS indicate that superoxide radical (O O 2 and NO contribute 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135207 16014720 179153 14535 7873 NOS2A iNOS iNOS-dependent 40 2.2 Pennathur et al. 1999 for the most part in an iNOS-dependent manner (Liberatore Liberatore et al. 1999 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135208 16014720 179156 13419 7218 MPO MPO MPO 2 7.1 Conversely myeloperoxidase (MPO), MPO and not ONOO seems to promote O O '-dityrosine formation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135209 16014720 179157 13419 7218 MPO MPO MPO 1 7.1 Moreover MPO can use the NO degradation product NO 2 to generate 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135210 16014720 179157 13419 7218 MPO MPO MPO 29 7.1 Vliet et al. 1997 and studies of mice deficient in MPO demonstrate that this enzyme is one of the major sources 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135211 16014720 179157 6981 22140 FAM20C RNS RNS 15 0.0 degradation product NO 2 to generate reactive nitrogen species (RNS) RNS (van van der Vliet et al. 1997 and studies of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135212 16014720 179158 13419 7218 MPO MPO MPO 8 7.1 Thus these results raise the unanticipated possibility that MPO a heme enzyme expressed in abundance in a variety of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135213 16014720 179159 13419 7218 MPO MPO MPO 10 7.1 Consistent with this hypothesis we show here not only that MPO is detected in affected brain areas of MPTP-injected mice and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135214 16014720 179159 13419 7218 MPO MPO MPO 34 7.1 in glial cells but also that mutant mice deficient in MPO are more resistant to MPTP-induced dopaminergic neurotoxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135215 16014720 179160 13419 7218 MPO MPO MPO 4 7.1 These findings indicate that MPO does participate in the MPTP neurotoxic process and suggest that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135216 16014720 179160 13419 7218 MPO MPO MPO 17 7.1 in the MPTP neurotoxic process and suggest that inhibitors of MPO may provide protective benefit in PD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135217 16014720 179163 13419 7218 MPO MPO MPO-deficient 19 1.0 C57BL 6J mice ( Charles River Laboratories Wilmington MA and MPO-deficient mice that had been backcrossed >10 times into the C57BL/6J 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135218 16014720 179169 211 132 ACTB beta-actin beta-actin 28 0.3 transcription-PCR analysis as described previously (Wu Wu et al. 2003 beta-actin were as follows MPO 5'-AGGATAGGACTGGATTGCCTG-3' (forward) forward and 5'-GTGGTGATGCCAGTGTTGTCA-3' (reverse); 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135219 16014720 179169 13419 7218 MPO MPO MPO 32 7.1 previously (Wu Wu et al. 2003 beta-actin were as follows MPO 5'-AGGATAGGACTGGATTGCCTG-3' (forward) forward and 5'-GTGGTGATGCCAGTGTTGTCA-3' (reverse); reverse beta-actin 5'-CTTTGATGTCACGCACGATTTC-3' (forward) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135220 16014720 179169 211 132 ACTB beta-actin beta-actin 38 0.3 as follows MPO 5'-AGGATAGGACTGGATTGCCTG-3' (forward) forward and 5'-GTGGTGATGCCAGTGTTGTCA-3' (reverse); reverse beta-actin 5'-CTTTGATGTCACGCACGATTTC-3' (forward) forward and 5'-GGGCCGCTCTAGGCACCAA-3' (reverse) reverse 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135221 16014720 179174 211 132 ACTB beta-actin beta-actin 22 0.3 blot analysis as described previously (Wu Wu et al. 2003 beta-actin antibody (1:10,000; 1 10 000 Sigma St Louis MO 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135222 16014720 179177 13419 7218 MPO MPO MPO 0 7.1 MPO isolation and activity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135223 16014720 179178 13419 7218 MPO MPO MPO 10 7.1 The methods used to prepare brain samples and to measure MPO activity are slight modifications of those described previously by Daugherty 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135224 16014720 179180 13419 7218 MPO MPO MPO 13 7.1 centrifugation final supernatants were collected and used immediately to assess MPO activity by monitoring the oxidation of tetramethylbenzidine as described previously 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135225 16014720 179182 13419 7218 MPO MPO MPO 1 7.1 Mouse MPO glial fibrillary acidic protein beta 2 integrin MAC-1 (CD116/CD18), CD116 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135226 16014720 179182 10731 6149 ITGAM MAC-1 MAC-1 9 2.8 Mouse MPO glial fibrillary acidic protein beta 2 integrin MAC-1 (CD116/CD18), CD116 CD18 neutrophil and tyrosine hydroxylase immunohistochemistry 1 JUMiner_v2.2 1 0 0 2 6155 TotalCon:2<>6149|ITGAM|3684|Complete__6155|ITGB2|3689|Complete__<>AvaiableGeneRif=2<>BEST:6155|ITGB2|0.000468139564827663<>ScoreDetail__6155|ITGB2|0.000468139564827663__6149|ITGAM|0.000412395616349507__ 0 0 0 0 0 135227 16014720 179182 5011 2435 CSF2RA CD116 CD116 10 1.3 MPO glial fibrillary acidic protein beta 2 integrin MAC-1 (CD116/CD18), CD116 CD18 neutrophil and tyrosine hydroxylase immunohistochemistry 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135228 16014720 179182 10739 6155 ITGB2 CD18 CD18 10 2.8 glial fibrillary acidic protein beta 2 integrin MAC-1 (CD116/CD18), CD116 CD18 neutrophil and tyrosine hydroxylase immunohistochemistry 1 JUMiner_v2.2 1 0 0 2 6155 TotalCon:2<>6155|ITGB2|3689|Complete__6718|LTBR|4055|Complete__<>AvaiableGeneRif=2<>BEST:6155|ITGB2|0.000457443933293814<>ScoreDetail__6718|LTBR|0.000408828940383034__6155|ITGB2|0.000457443933293814__ 0 0 0 0 0 135229 16014720 179184 8254 4235 GFAP GFAP GFAP 19 2.5 Vision Fremont CA rabbit polyclonal anti-glial fibrillary acidic protein (GFAP; GFAP 1 500 Chemicon Temecula CA mouse monoclonal anti-MAC-1 (1:1000; 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135230 16014720 179196 20996 11179 SOD1 ALS ALS 34 0.3 and the frontal motor cortex for amyotrophic lateral sclerosis (ALS) ALS or motor neuron disease and controls 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00056102382469375<>ScoreDetail__5468|IGFALS|0.000352634551292419__11179|SOD1|0.00056102382469375__ 0 0 0 0 0 135231 16014720 179197 20996 11179 SOD1 ALS ALS 20 0.3 neuropathological diagnoses using the criteria for definite PD HD and ALS outlined in the supplemental material (available available at www.jneurosci.org 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00056102382469375<>ScoreDetail__5468|IGFALS|0.000352634551292419__11179|SOD1|0.00056102382469375__ 0 0 0 0 0 135232 16014720 179199 13419 7218 MPO MPO MPO 28 7.1 mouse tissues the primary anti-MPO antibody was a rabbit anti-human MPO antibody (DakoCytomation, DakoCytomation Carpinteria CA used at 1 1000 for 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135233 16014720 179202 13419 7218 MPO MPO MPO-deficient 19 1.0 with UV detection ( = 295 nm in WT and MPO-deficient mice at 90 min after the last injection of 20 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135234 16014720 179202 13412 7214 MPHOSPH6 MPP MPP 2 0.0 Striatal 1-methyl-4-phenylpyridinium (MPP MPP levels were determined by HPLC with UV detection ( = 1 JUMiner_v2.2 1 0 0 2 7214 TotalCon:2<>7214|MPHOSPH6|10200|Complete__7225|MPZ|4359|Complete__<>AvaiableGeneRif=2<>BEST:7214|MPHOSPH6|0.000481293134762078<>ScoreDetail__7214|MPHOSPH6|0.000481293134762078__7225|MPZ|0.000398765781984089__ 0 0 0 0 0 135235 16014720 179203 13412 7214 MPHOSPH6 MPP MPP 6 0.0 Striatal tissue lactate production induced by MPP and synaptosomal uptake of H MPP were performed as described 1 JUMiner_v2.2 1 0 0 2 7214 TotalCon:2<>7214|MPHOSPH6|10200|Complete__7225|MPZ|4359|Complete__<>AvaiableGeneRif=2<>BEST:7214|MPHOSPH6|0.000481293134762078<>ScoreDetail__7214|MPHOSPH6|0.000481293134762078__7225|MPZ|0.000398765781984089__ 0 0 0 0 0 135236 16014720 179203 13412 7214 MPHOSPH6 MPP MPP 12 0.0 lactate production induced by MPP and synaptosomal uptake of H MPP were performed as described previously (Wu Wu et al. 2003 1 JUMiner_v2.2 1 0 0 2 7214 TotalCon:2<>7214|MPHOSPH6|10200|Complete__7225|MPZ|4359|Complete__<>AvaiableGeneRif=2<>BEST:7214|MPHOSPH6|0.000481293134762078<>ScoreDetail__7214|MPHOSPH6|0.000481293134762078__7225|MPZ|0.000398765781984089__ 0 0 0 0 0 135237 16014720 179208 1552 30000 BBS9 C18 C-18 7 0.0 The amino acids were isolated using a C-18 solid-phase extraction column and subjected to derivatization and analysis by 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135238 16014720 179218 13419 7218 MPO MPO MPO 0 7.1 MPO is induced in the mouse ventral midbrain during MPTP-induced dopaminergic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135239 16014720 179219 13419 7218 MPO MPO MPO 5 7.1 To examine the possibility that MPO is a component of the inflammatory response seen in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135240 16014720 179219 13419 7218 MPO MPO MPO 33 7.1 et al. 1999 Wu et al. 2002 we first assessed MPO mRNA and protein content in the ventral midbrain (i.e., i.e. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135241 16014720 179220 13419 7218 MPO MPO MPO 11 7.1 saline-injected control mice the ventral midbrain contained low levels of MPO mRNA and protein ( Fig 1 A-C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135242 16014720 179221 13419 7218 MPO MPO MPO 10 7.1 In contrast in MPTP-injected mice ventral midbrain levels of both MPO mRNA and protein increased in a time-dependent manner ( Fig 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135243 16014720 179222 13419 7218 MPO MPO MPO 2 7.1 Ventral midbrain MPO mRNA and protein expression levels peaked at 1 and 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135244 16014720 179223 13419 7218 MPO MPO MPO 8 7.1 We next asked whether the observed changes in MPO ventral midbrain content in MPTP-injected animals paralleled an alteration of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135245 16014720 179223 13419 7218 MPO MPO MPO 19 7.1 ventral midbrain content in MPTP-injected animals paralleled an alteration of MPO enzymatic activity by monitoring oxidation of tetramethylbenzidine 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135246 16014720 179224 13419 7218 MPO MPO MPO 10 7.1 Consistent with the protein data we found that ventral midbrain MPO activity also rose during MPTP neurotoxicity in a time-dependent manner 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135247 16014720 179225 13419 7218 MPO MPO MPO 7 7.1 In contrast in mutant mice deficient in MPO (MPO MPO n = 2 the ventral midbrain did not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135248 16014720 179225 13419 7218 MPO MPO MPO 8 7.1 In contrast in mutant mice deficient in MPO (MPO MPO n = 2 the ventral midbrain did not show higher 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135249 16014720 179226 13419 7218 MPO MPO MPO 7 7.1 Unlike in the ventral midbrain levels of MPO mRNA proteins and catalytic activity in the cerebellum (brain brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135250 16014720 179227 13419 7218 MPO MPO MPO 8 7.1 However more unexpected was the finding that no MPO alteration could be detected in the striatum (where where dopaminergic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135251 16014720 179227 13419 7218 MPO MPO MPO 32 7.1 administration as illustrated by the lack of change in striatal MPO activity saline 14.0 _amp_#177 4.1 ( n = 7 versus 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135252 16014720 179228 13419 7218 MPO MPO MPO 7 7.1 Thus both protein levels and activity of MPO increase in the MPTP mouse model of PD specifically in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135253 16014720 179229 13419 7218 MPO MPO MPO 8 7.1 The present study shows that the level of MPO expression increases markedly in diseased SNpc from both mice exposed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135254 16014720 179230 13419 7218 MPO MPO MPO 7 7.1 This work also demonstrates that changes of MPO protein content and enzymatic activity in MPTP-intoxicated mice parallel ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135255 16014720 179231 13419 7218 MPO MPO MPO 1 7.1 Moreover MPO is found primarily in SNpc-reactive astrocytes (Figs Figs 2 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135256 16014720 179232 13419 7218 MPO MPO MPO 13 7.1 to detect any of the well established cellular sources of MPO (neutrophils, neutrophils monocytes or macrophages (Hampton Hampton et al. 1998 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135257 16014720 179233 13419 7218 MPO MPO MPO 3 7.1 The presence of MPO in damaged SNpc thus appears to derive essentially from a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135258 16014720 179234 20996 11179 SOD1 ALS ALS 12 0.3 assessments performed in two other neurodegenerative diseases namely HD and ALS it appears that MPO upregulation in the brain is not 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00056102382469375<>ScoreDetail__5468|IGFALS|0.000352634551292419__11179|SOD1|0.00056102382469375__ 0 0 0 0 0 135259 16014720 179234 13419 7218 MPO MPO MPO 16 7.1 other neurodegenerative diseases namely HD and ALS it appears that MPO upregulation in the brain is not pathognomonic of PD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135260 16014720 179235 13419 7218 MPO MPO MPO 7 7.1 Instead we believe that the occurrence of MPO in diseased brains is likely indicative of a disease process 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135261 16014720 179236 13419 7218 MPO MPO MPO 21 7.1 are generally believed to be the only cellular sources of MPO 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135262 16014720 179237 13419 7218 MPO MPO MPO 4 7.1 However neuronal expression of MPO is also increased in Alzheimer's disease (Green Green et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135263 16014720 179239 13419 7218 MPO MPO MPO 11 7.1 injections are associated with a time-dependent increase in ventral midbrain MPO mRNA ( A C protein expression ( B C and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135264 16014720 179243 13419 7218 MPO MPO MPO 9 7.1 A C Immunochemical studies revealed no specific MPO immunoreactivity in the ventral midbrain of saline-injected control mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135265 16014720 179245 13419 7218 MPO MPO MPO 16 7.1 dense network of fibers and scattered cell bodies positive for MPO are seen at the level of the SNpc after MPTP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135266 16014720 179246 13419 7218 MPO MPO MPO-positive 6 1.0 Black arrows in D show the MPO-positive cellular elements 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135267 16014720 179247 13419 7218 MPO MPO MPO-positive 8 1.0 E-H Confocal microscopy demonstrates that ventral midbrain MPO-positive structures ( E red are also GFAP positive ( F 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135268 16014720 179247 8254 4235 GFAP GFAP GFAP 16 2.5 that ventral midbrain MPO-positive structures ( E red are also GFAP positive ( F green as evidenced by the overlay of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135269 16014720 179248 13419 7218 MPO MPO MPO-positive 6 1.0 J-L In contrast ventral midbrain MPO-positive structures ( I red are not MAC-1 positive ( J 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135270 16014720 179248 10731 6149 ITGAM MAC-1 MAC-1 14 2.8 contrast ventral midbrain MPO-positive structures ( I red are not MAC-1 positive ( J green as evidenced by the overlay ( 1 JUMiner_v2.2 1 0 0 2 6155 TotalCon:2<>6149|ITGAM|3684|Complete__6155|ITGB2|3689|Complete__<>AvaiableGeneRif=2<>BEST:6155|ITGB2|0.000468139564827663<>ScoreDetail__6155|ITGB2|0.000468139564827663__6149|ITGAM|0.000412395616349507__ 0 0 0 0 0 135271 16014720 179252 13419 7218 MPO MPO MPO 6 7.1 A B Ventral midbrain MPO tissue content is increased in postmortem tissue from PD patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135272 16014720 179252 8254 4235 GFAP GFAP GFAP 23 2.5 tissue from PD patients compared with controls as well as GFAP tissue content 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135273 16014720 179253 13419 7218 MPO MPO MPO 4 7.1 C Positive control (purified purified MPO 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135274 16014720 179254 13419 7218 MPO MPO MPO 5 7.1 C Inventral midbrain sections MPO (blue) blue is not detected in control tissues neither in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135275 16014720 179254 8254 4235 GFAP GFAP GFAP-positive 15 2.5 (blue) blue is not detected in control tissues neither in GFAP-positive cells (open open arrow nor in or around neuromelanized dopaminergic 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 135276 16014720 179255 13419 7218 MPO MPO MPO 3 7.1 D Conversely MPO immunoreactivity (blue, blue small black arrow is found in GFAP-positive 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135277 16014720 179255 8254 4235 GFAP GFAP GFAP-positive 12 2.5 MPO immunoreactivity (blue, blue small black arrow is found in GFAP-positive cells (open open arrow in PD tissue but not in 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 135278 16014720 179259 13419 7218 MPO MPO MPO 4 7.1 A-D Ablation of MPO in mutant mice attenuates MPTP-induced striatal TH fibers and SNpc 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135279 16014720 179261 13419 7218 MPO MPO MPO 27 7.1 saline-injected animals p _lt_ 0.05 compared with saline- and MPTP-injected MPO mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135280 16014720 179264 9518 24961 HOPX HOP HOP-1-positive 5 0.3 Twenty-four hours after MPTP injections HOP-1-positive immunoreactive material is seen mainly at the level of the 11 JUMiner_v2.2 1 0 0 2 24961 TotalCon:3<>24961|HOPX|84525|Complete__11343|ST13|6767|Complete__11387|STIP1|10963|Complete__<>AvaiableGeneRif=3<>BEST:24961|HOPX|0.000515262810940254<>ScoreDetail__11387|STIP1|0.000278484077975542__24961|HOPX|0.000515262810940254__11343|ST13|0.000462475799596317__ 0 0 0 0 0 135281 16014720 179267 13419 7218 MPO MPO MPO-deficient 4 1.0 Striatal MPTP metabolism in MPO-deficient mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135282 16014720 179268 13419 7218 MPO MPO MPO 0 7.1 MPO is expressed in reactive astrocytes after MPTP injection 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135283 16014720 179269 13419 7218 MPO MPO MPO 6 7.1 To elucidate the cellular origin of MPO in the ventral midbrain of MPTP-treated mice immunohistochemical studies were 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135284 16014720 179270 13419 7218 MPO MPO MPO 4 7.1 In saline controls diffuse MPO immunoreactivity was seen in the neuropil ( Fig 2 A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135285 16014720 179271 13419 7218 MPO MPO MPO 11 7.1 MPTP-treated mice 2 d after the last injection ventral midbrain MPO immunostaining was stronger especially at the level of the substantia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135286 16014720 179272 13419 7218 MPO MPO MPO-positive 1 1.0 These MPO-positive cells showed punctate immunoreactivity over both the cell bodies and 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 135287 16014720 179274 13419 7218 MPO MPO MPO 4 7.1 This analysis confirmed that MPO colocalized with the astrocytic marker GFAP as shown by the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135288 16014720 179274 8254 4235 GFAP GFAP GFAP 10 2.5 This analysis confirmed that MPO colocalized with the astrocytic marker GFAP as shown by the merged image from the two fluorochromes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135289 16014720 179275 13419 7218 MPO MPO MPO 4 7.1 Conversely no evidence of MPO expression in microglial cells could be documented by using the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135290 16014720 179277 13419 7218 MPO MPO MPO 3 7.1 No noticeable cellular MPO immunoreactivity was observed in the striatum or cerebellum of either 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135291 16014720 179278 13419 7218 MPO MPO MPO 4 7.1 These results demonstrate that MPO is primarily expressed in ventral midbrain astrocytes during the demise 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135292 16014720 179279 13419 7218 MPO MPO MPO 2 7.1 Expression of MPO is increased in PD midbrain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135293 16014720 179280 13419 7218 MPO MPO MPO 6 7.1 To determine whether the changes in MPO observed in the MPTP mouse model of PD were present 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135294 16014720 179280 13419 7218 MPO MPO MPO 23 7.1 of PD were present in the human condition we assessed MPO protein levels in postmortem ventral midbrain samples from sporadic PD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135295 16014720 179281 13419 7218 MPO MPO MPO 10 7.1 Consistent with the mouse data PD samples had significantly higher MPO protein contents compared with controls ( Fig 3 A B 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135296 16014720 179282 13419 7218 MPO MPO MPO 9 7.1 Like in mice there was no significant difference in MPO to beta-actin ratios in the striatum (PD, PD 1.1 _amp_#177 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135297 16014720 179282 211 132 ACTB beta-actin beta-actin 11 0.3 in mice there was no significant difference in MPO to beta-actin ratios in the striatum (PD, PD 1.1 _amp_#177 0.8 vs 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135298 16014720 179283 13419 7218 MPO MPO MPO 2 7.1 Histologically cellular MPO immunoreactivity was not detected in the control ventral midbrain parenchyma 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135299 16014720 179284 13419 7218 MPO MPO MPO 1 7.1 However MPO immunoreactivity was seen in ventral midbrain sections from PD patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135300 16014720 179285 13419 7218 MPO MPO MPO 4 7.1 The similarity of the MPO alterations between the MPTP mice and the PD postmortem specimens 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135301 16014720 179285 13419 7218 MPO MPO MPO 28 7.1 of using this experimental model to study the role of MPO in the PD neurodegenerative process 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135302 16014720 179286 13419 7218 MPO MPO MPO 19 7.1 neurodegenerative diseases we wondered whether increases in the expression of MPO within areas of neurodegeneration can be found in neurodegenerative disorders 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135303 16014720 179287 20996 11179 SOD1 ALS ALS 7 0.3 Compared with controls the motor cortex from ALS patients did not exhibit higher GFAP or MPO values (data 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00056102382469375<>ScoreDetail__5468|IGFALS|0.000352634551292419__11179|SOD1|0.00056102382469375__ 0 0 0 0 0 135304 16014720 179287 8254 4235 GFAP GFAP GFAP 13 2.5 the motor cortex from ALS patients did not exhibit higher GFAP or MPO values (data data not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135305 16014720 179287 13419 7218 MPO MPO MPO 15 7.1 cortex from ALS patients did not exhibit higher GFAP or MPO values (data data not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135306 16014720 179288 8254 4235 GFAP GFAP GFAP 14 2.5 caudate nucleus tissues from stage 4 HD patients had higher GFAP to beta-actin ratios (HD, HD 0.7 _amp_#177 0.1 vs controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135307 16014720 179288 211 132 ACTB beta-actin beta-actin 16 0.3 tissues from stage 4 HD patients had higher GFAP to beta-actin ratios (HD, HD 0.7 _amp_#177 0.1 vs controls 0.1 _amp_#177 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135308 16014720 179288 13419 7218 MPO MPO MPO 36 7.1 0.1 p _lt_ 0.01 n = 3-4 as well as MPO to beta-actin ratios (HD, HD 0.8 _amp_#177 0.2 vs controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135309 16014720 179288 211 132 ACTB beta-actin beta-actin 38 0.3 _lt_ 0.01 n = 3-4 as well as MPO to beta-actin ratios (HD, HD 0.8 _amp_#177 0.2 vs controls 0.2 _amp_#177 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135310 16014720 179289 13419 7218 MPO MPO MPO 4 7.1 This suggests that brain MPO expression is not specific to PD but rather generic to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135311 16014720 179290 13419 7218 MPO MPO MPO 0 7.1 MPO deficiency protects against MPTP-induced neurodegeneration 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135312 16014720 179291 13419 7218 MPO MPO MPO 16 7.1 MPTP on the nigrostriatal pathway of mutant mice deficient in MPO (MPO MPO and their WT littermates (MPO MPO 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135313 16014720 179291 13419 7218 MPO MPO MPO 17 7.1 the nigrostriatal pathway of mutant mice deficient in MPO (MPO MPO and their WT littermates (MPO MPO 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135314 16014720 179291 13419 7218 MPO MPO MPO 23 7.1 deficient in MPO (MPO MPO and their WT littermates (MPO MPO 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135315 16014720 179293 13419 7218 MPO MPO MPO 2 7.1 In saline-injected MPO and MPO mice stereological counts of SNpc dopaminergic neurons and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135316 16014720 179293 13419 7218 MPO MPO MPO 4 7.1 In saline-injected MPO and MPO mice stereological counts of SNpc dopaminergic neurons and striatal TH-positive 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135317 16014720 179294 13419 7218 MPO MPO MPO 2 7.1 In MPTP-injected MPO mice there was a ~70% loss of SNpc TH-positive neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135318 16014720 179295 13419 7218 MPO MPO MPO 4 7.1 In contrast in MPTP-injected MPO mice there was only ~50% loss of SNpc TH-positive neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135319 16014720 179297 13419 7218 MPO MPO MPO 3 7.1 To examine whether MPO ablation protects not only against structural damage but also against 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135320 16014720 179297 13419 7218 MPO MPO MPO 42 7.1 acid in the striatum as well as locomotor activity between MPO and MPO mice after MPTP injections 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135321 16014720 179297 13419 7218 MPO MPO MPO 44 7.1 the striatum as well as locomotor activity between MPO and MPO mice after MPTP injections 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135322 16014720 179298 13419 7218 MPO MPO MPO 9 7.1 Contrasting with the protection afforded by the lack of MPO on the nigrostriatal dopaminergic neurons the loss of striatal dopamine 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135323 16014720 179298 13419 7218 MPO MPO MPO 33 7.1 in motor performance caused by MPTP were as severe in MPO as in MPO mice ( supplemental material available at www.jneurosci.org 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135324 16014720 179298 13419 7218 MPO MPO MPO 36 7.1 caused by MPTP were as severe in MPO as in MPO mice ( supplemental material available at www.jneurosci.org 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135325 16014720 179300 13412 7214 MPHOSPH6 MPP MPP 12 0.0 controlling MPTP neurotoxicity are its conversion in the brain to MPP followed by MPP entry into dopaminergic neurons and its subsequent 1 JUMiner_v2.2 1 0 0 2 7214 TotalCon:2<>7214|MPHOSPH6|10200|Complete__7225|MPZ|4359|Complete__<>AvaiableGeneRif=2<>BEST:7214|MPHOSPH6|0.000481293134762078<>ScoreDetail__7214|MPHOSPH6|0.000481293134762078__7225|MPZ|0.000398765781984089__ 0 0 0 0 0 135326 16014720 179300 13412 7214 MPHOSPH6 MPP MPP 16 0.0 are its conversion in the brain to MPP followed by MPP entry into dopaminergic neurons and its subsequent blockade of mitochondrial 1 JUMiner_v2.2 1 0 0 2 7214 TotalCon:2<>7214|MPHOSPH6|10200|Complete__7225|MPZ|4359|Complete__<>AvaiableGeneRif=2<>BEST:7214|MPHOSPH6|0.000481293134762078<>ScoreDetail__7214|MPHOSPH6|0.000481293134762078__7225|MPZ|0.000398765781984089__ 0 0 0 0 0 135327 16014720 179301 13419 7218 MPO MPO MPO 6 7.1 To ascertain that the resistance of MPO mice was not attributable to alterations in MPTP toxicokinetics we 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135328 16014720 179302 13419 7218 MPO MPO MPO 28 7.1 (a a measure of mitochondrial function did not differ between MPO mice and their WT littermates ( Table 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135329 16014720 179302 13412 7214 MPHOSPH6 MPP MPP 6 0.0 Results show that striatal levels of MPP striatal uptake of H MPP and MPP -induced lactate production 1 JUMiner_v2.2 1 0 0 2 7214 TotalCon:2<>7214|MPHOSPH6|10200|Complete__7225|MPZ|4359|Complete__<>AvaiableGeneRif=2<>BEST:7214|MPHOSPH6|0.000481293134762078<>ScoreDetail__7214|MPHOSPH6|0.000481293134762078__7225|MPZ|0.000398765781984089__ 0 0 0 0 0 135330 16014720 179302 13412 7214 MPHOSPH6 MPP MPP 12 0.0 show that striatal levels of MPP striatal uptake of H MPP and MPP -induced lactate production (a a measure of mitochondrial 1 JUMiner_v2.2 1 0 0 2 7214 TotalCon:2<>7214|MPHOSPH6|10200|Complete__7225|MPZ|4359|Complete__<>AvaiableGeneRif=2<>BEST:7214|MPHOSPH6|0.000481293134762078<>ScoreDetail__7214|MPHOSPH6|0.000481293134762078__7225|MPZ|0.000398765781984089__ 0 0 0 0 0 135331 16014720 179302 13412 7214 MPHOSPH6 MPP MPP 15 0.0 striatal levels of MPP striatal uptake of H MPP and MPP -induced lactate production (a a measure of mitochondrial function did 1 JUMiner_v2.2 1 0 0 2 7214 TotalCon:2<>7214|MPHOSPH6|10200|Complete__7225|MPZ|4359|Complete__<>AvaiableGeneRif=2<>BEST:7214|MPHOSPH6|0.000481293134762078<>ScoreDetail__7214|MPHOSPH6|0.000481293134762078__7225|MPZ|0.000398765781984089__ 0 0 0 0 0 135332 16014720 179303 13419 7218 MPO MPO MPO 0 7.1 MPO damages ventral midbrain proteins 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135333 16014720 179304 13419 7218 MPO MPO MPO 0 7.1 MPO is the only known mammalian source of HOCl at plasma 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135334 16014720 179305 13419 7218 MPO MPO MPO 16 7.1 3-chlorotyrosine a specific and stable biomarker of protein damage by MPO (Heinecke Heinecke et al. 1999 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135335 16014720 179309 13419 7218 MPO MPO MPO 4 7.1 In contrast in MPTP-treated MPO mice ( n = 3 ventral midbrain 3-chlorotyrosine was undetectable 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135336 16014720 179310 13419 7218 MPO MPO MPO 16 7.1 tissues therefore supports the hypothesis that reactive intermediates produced by MPO damage brain proteins in MPTP-intoxicated mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135337 16014720 179311 13419 7218 MPO MPO MPO-damaged 2 1.5 To localize MPO-damaged proteins tissue sections were immunostained with HOP-1 a mouse antibody 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135338 16014720 179313 9518 24961 HOPX HOP HOP-1-positive 0 0.3 HOP-1-positive material was seen in the neuropil within beaded-appearing fibers and 11 JUMiner_v2.2 1 0 0 2 24961 TotalCon:3<>24961|HOPX|84525|Complete__11343|ST13|6767|Complete__11387|STIP1|10963|Complete__<>AvaiableGeneRif=3<>BEST:24961|HOPX|0.000515262810940254<>ScoreDetail__11387|STIP1|0.000278484077975542__24961|HOPX|0.000515262810940254__11343|ST13|0.000462475799596317__ 0 0 0 0 0 135339 16014720 179314 13419 7218 MPO MPO MPO 13 7.1 was detected in the SNpc of saline-injected mice or MPTP-injected MPO mice (data data not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135340 16014720 179315 13419 7218 MPO MPO MPO 29 7.1 and sometimes in PD did not show any alteration in MPO expression or enzymatic activity as illustrated in Figure 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135341 16014720 179316 14535 7873 NOS2A iNOS iNOS 4 2.2 Remarkably detectable changes in iNOS expression and enzymatic activity are also confined to ventral midbrains 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135342 16014720 179320 13419 7218 MPO MPO MPO 7 7.1 After MPTP injections mutant mice deficient in MPO showed more spared SNpc dopaminergic neurons and striatal dopaminergic fibers 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135343 16014720 179321 13419 7218 MPO MPO MPO 7 7.1 We also found that the lack of MPO did not alter key aspects of MPTP toxicokinetics ( Table 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135344 16014720 179322 13419 7218 MPO MPO MPO 5 7.1 Together these findings indicate that MPO contributes to the pathogenic cascade of deleterious events responsible for 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135345 16014720 179323 13419 7218 MPO MPO MPO 4 7.1 Surprisingly although alterations in MPO protein and enzymatic activity were only detected in the ventral 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135346 16014720 179323 13419 7218 MPO MPO MPO 33 7.1 and fibers of nigrostriatal dopaminergic neurons were preserved in MPTP-injected MPO mice ( Fig 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135347 16014720 179325 13419 7218 MPO MPO MPO 10 7.1 The relative resistance of dopaminergic neurons to MPTP-induced neurotoxicity in MPO mice was however not accompanied by a preservation of striatal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135348 16014720 179327 13419 7218 MPO MPO MPO 8 7.1 It is thus conceivable that although ablation of MPO attenuates the loss of TH protein (as as evidenced by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135349 16014720 179328 13419 7218 MPO MPO MPO 1 7.1 Targeting MPO alone may thus suffice to provide observable structural but not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135350 16014720 179329 13419 7218 MPO MPO MPO 20 7.1 combination of strategies capable of providing structural protection such as MPO inhibition with other strategies capable of protecting/stimulating protecting stimulating dopaminergic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135351 16014720 179331 13419 7218 MPO MPO MPO 2 7.1 Therefore whether MPO inhibition in PD can succeed not only in slowing neuronal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135352 16014720 179332 13419 7218 MPO MPO MPO 3 7.1 As to how MPO neurotoxic actions on dopaminergic neurons are mediated two distinct and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135353 16014720 179333 13419 7218 MPO MPO MPO 3 7.1 First and foremost MPO is known for its production of cytotoxic reactive oxygen species 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135354 16014720 179333 6981 22140 FAM20C RNS RNS 15 0.0 known for its production of cytotoxic reactive oxygen species and RNS (Harrison Harrison and Schultz 1976 Eiserich et al. 1996 Hampton 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135355 16014720 179334 13419 7218 MPO MPO MPO-containing 7 1.0 Therefore neurons located in the vicinity of MPO-containing cells may have their plasma membrane proteins and lipids subjected 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 135356 16014720 179334 13419 7218 MPO MPO MPO-derived 23 1.0 membrane proteins and lipids subjected to the deleterious effects of MPO-derived oxidants such as HOCl 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135357 16014720 179336 13419 7218 MPO MPO MPO 6 7.1 Also supporting the oxidative role of MPO in the MPTP model is our immunohistochemical demonstration of HOCl-modified 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135358 16014720 179337 13419 7218 MPO MPO MPO 5 7.1 Aside from this oxidative effect MPO can be secreted and bind CD11b/CD18 CD11b CD18 integrins to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135359 16014720 179337 10731 6149 ITGAM CD11b CD11b 11 2.8 this oxidative effect MPO can be secreted and bind CD11b/CD18 CD11b CD18 integrins to the cell surface (Lau Lau et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135360 16014720 179337 10739 6155 ITGB2 CD18 CD18 11 2.8 oxidative effect MPO can be secreted and bind CD11b/CD18 CD11b CD18 integrins to the cell surface (Lau Lau et al. 2005 1 JUMiner_v2.2 1 0 0 2 6155 TotalCon:2<>6155|ITGB2|3689|Complete__6718|LTBR|4055|Complete__<>AvaiableGeneRif=2<>BEST:6155|ITGB2|0.000457443933293814<>ScoreDetail__6718|LTBR|0.000408828940383034__6155|ITGB2|0.000457443933293814__ 0 0 0 0 0 135361 16014720 179338 10731 6149 ITGAM CD11b CD11b 7 2.8 In the case of neutrophils ligation of CD11b/CD18 CD11b CD18 by MPO stimulates signaling pathways implicated in the activation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135362 16014720 179338 10739 6155 ITGB2 CD18 CD18 7 2.8 In the case of neutrophils ligation of CD11b/CD18 CD11b CD18 by MPO stimulates signaling pathways implicated in the activation of 1 JUMiner_v2.2 1 0 0 2 6155 TotalCon:2<>6155|ITGB2|3689|Complete__6718|LTBR|4055|Complete__<>AvaiableGeneRif=2<>BEST:6155|ITGB2|0.000457443933293814<>ScoreDetail__6718|LTBR|0.000408828940383034__6155|ITGB2|0.000457443933293814__ 0 0 0 0 0 135363 16014720 179338 13419 7218 MPO MPO MPO 9 7.1 the case of neutrophils ligation of CD11b/CD18 CD11b CD18 by MPO stimulates signaling pathways implicated in the activation of these cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135364 16014720 179339 10731 6149 ITGAM CD11b CD11b 5 2.8 Because brain microglia do express CD11b/CD18 CD11b CD18 integrins and seem to participate in the neurodegenerative process 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 135365 16014720 179339 10739 6155 ITGB2 CD18 CD18 5 2.8 Because brain microglia do express CD11b/CD18 CD11b CD18 integrins and seem to participate in the neurodegenerative process in 1 JUMiner_v2.2 1 0 0 2 6155 TotalCon:2<>6155|ITGB2|3689|Complete__6718|LTBR|4055|Complete__<>AvaiableGeneRif=2<>BEST:6155|ITGB2|0.000457443933293814<>ScoreDetail__6718|LTBR|0.000408828940383034__6155|ITGB2|0.000457443933293814__ 0 0 0 0 0 135366 16014720 179339 13419 7218 MPO MPO MPO 26 7.1 the MPTP model and in PD this cytokine-like effect of MPO may represent an additional mechanism by which dopaminergic neurons are 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140248 16101543 184879 20996 11179 SOD1 ALS ALS 12 0.0 such as Parkinson's disease Alzheimer's disease amyotrophic lateral sclerosis (ALS), ALS Huntington stroke head trauma and infection are associated with inflammation 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000657028209296694<>ScoreDetail__5468|IGFALS|0.000261726815366272__11179|SOD1|0.000657028209296694__ 0 0 0 0 0 140249 16101543 184883 17609 9604 PTGS1 COX-1 COX-1 17 0.3 by two isoforms of the cyclooxygenase (COX) COX enzyme namely COX-1 and COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140250 16101543 184883 17610 9605 PTGS2 COX-2 COX-2 17 1.3 by two isoforms of the cyclooxygenase (COX) COX enzyme namely COX-1 and COX-2 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140251 16101543 184883 17610 9605 PTGS2 COX-2 COX-2 19 1.3 isoforms of the cyclooxygenase (COX) COX enzyme namely COX-1 and COX-2 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140252 16101543 184883 17610 9605 PTGS2 COX COX 14 0.0 acid (AA) AA by two isoforms of the cyclooxygenase (COX) COX enzyme namely COX-1 and COX-2 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 140253 16101543 184884 17610 9605 PTGS2 COX-2 COX-2 5 1.3 In particular the action of COX-2 and PGs in CNS inflammation has gained much attention recently 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140254 16101543 184887 17610 9605 PTGS2 COX COX 6 0.0 However accumulating evidence also shows that COX inhibitors alleviate various types of brain damage via suppressing inflammatory 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 140255 16101543 184888 17610 9605 PTGS2 COX COX 5 0.0 Accordingly the roles of two COX enzymes in mediating inflammation and anti-inflammation have recently been debated 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 140256 16101543 184889 17610 9605 PTGS2 COX COX 17 0.0 findings indicating that the reciprocal interaction of glial cell activation COX enzymes and PGs mediates neurodegeneration and neuroprotection during brain inflammation 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 140270 16104843 184910 23910 12680 VEGFA VEGF VEGF 5 10.4 Foremost among these is the VEGF (vascular vascular endothelial growth factor family and VEGFRs (VEGF VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140271 16104843 184910 10981 6307 KDR VEGFR VEGFRs 12 3.0 is the VEGF (vascular vascular endothelial growth factor family and VEGFRs (VEGF VEGF receptors 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140272 16104843 184910 23910 12680 VEGFA VEGF VEGF 13 10.4 VEGF (vascular vascular endothelial growth factor family and VEGFRs (VEGF VEGF receptors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140273 16104843 184911 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A also referred to as VPF (vascular vascular permeability factor an 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140274 16104843 184911 23910 12680 VEGFA VPF VPF 5 5.8 VEGF-A also referred to as VPF (vascular vascular permeability factor an important regulator of endothelial cell 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140275 16104843 184912 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A is a dimeric glycoprotein essential for many angiogenic processes in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140276 16104843 184912 7629 3763 FLT1 VEGFR1 VEGFR-1 27 0.6 tumour vascularization mainly by interacting with two tyrosine kinase receptors VEGFR-1 also known as Flt-1 (Fms-like Fms-like tyrosine kinase-1 and VEGFR-2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140277 16104843 184912 7629 3763 FLT1 FLT1 Flt-1 31 0.6 interacting with two tyrosine kinase receptors VEGFR-1 also known as Flt-1 (Fms-like Fms-like tyrosine kinase-1 and VEGFR-2 also known as Flk-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140278 16104843 184912 10981 6307 KDR VEGFR2 VEGFR-2 36 4.3 VEGFR-1 also known as Flt-1 (Fms-like Fms-like tyrosine kinase-1 and VEGFR-2 also known as Flk-1 (fetal fetal liver kinase-1 and in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140279 16104843 184912 10981 6307 KDR FLK1 Flk-1 40 3.0 Flt-1 (Fms-like Fms-like tyrosine kinase-1 and VEGFR-2 also known as Flk-1 (fetal fetal liver kinase-1 and in humans as KDR (kinase 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140280 16104843 184912 10981 6307 KDR KDR KDR 48 3.0 as Flk-1 (fetal fetal liver kinase-1 and in humans as KDR (kinase kinase insert domain-containing receptor 3-5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140281 16104843 184913 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A exhibits two major biological activities one is the capacity to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140282 16104843 184914 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A also promotes the survival and migration of endothelial cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140283 16104843 184915 23910 12680 VEGFA VEGF VEGF 18 10.4 biological functions and the precise molecular mechanisms of the VEGF/VEGFR VEGF VEGFR system 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140284 16104843 184915 10981 6307 KDR VEGFR VEGFR 18 3.3 functions and the precise molecular mechanisms of the VEGF/VEGFR VEGF VEGFR system 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140285 16104843 184916 23910 12680 VEGFA VEGF VEGF 15 10.4 the recent advances in the basic biology of the VEGF/VEGFR VEGF VEGFR system which give insight into many physiological and pathological 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140286 16104843 184916 10981 6307 KDR VEGFR VEGFR 15 3.3 recent advances in the basic biology of the VEGF/VEGFR VEGF VEGFR system which give insight into many physiological and pathological conditions 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140287 16104843 184917 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF AND VEGF FAMILY PROTEINS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140288 16104843 184917 23910 12680 VEGFA VEGF VEGF 2 10.4 VEGF AND VEGF FAMILY PROTEINS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140289 16104843 184918 23910 12680 VEGFA VEGF VEGF 2 10.4 Currently the VEGF family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140290 16104843 184918 23910 12680 VEGFA VEGF-A VEGF-A 5 7.6 Currently the VEGF family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140291 16104843 184918 16459 8893 PGF PlGF PlGF 6 4.6 Currently the VEGF family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and svVEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140292 16104843 184918 23911 12681 VEGFB VEGFB VEGF-B 10 1.8 the VEGF family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and svVEGF (snake snake venom VEGF 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140293 16104843 184918 23912 12682 VEGFC VEGFC VEGF-C 11 1.8 VEGF family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and svVEGF (snake snake venom VEGF 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140294 16104843 184918 7579 3708 FIGF VEGF-D VEGF-D 12 1.3 family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and svVEGF (snake snake venom VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140295 16104843 184918 23910 12680 VEGFA VEGF VEGF 18 10.4 factor VEGF-B VEGF-C VEGF-D VEGF-E and svVEGF (snake snake venom VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140296 16104843 184920 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140297 16104843 184921 23910 12680 VEGFA VEGF VEGF 1 10.4 Structurally VEGF belongs to the VEGF/PDGF VEGF PDGF (platelet-derived platelet-derived growth factor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140298 16104843 184921 23910 12680 VEGFA VEGF VEGF 5 10.4 Structurally VEGF belongs to the VEGF/PDGF VEGF PDGF (platelet-derived platelet-derived growth factor supergene family 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140299 16104843 184921 16316 8799 PDGFA PDGF PDGF 5 1.2 Structurally VEGF belongs to the VEGF/PDGF VEGF PDGF (platelet-derived platelet-derived growth factor supergene family 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140300 16104843 184924 23910 12680 VEGFA VEGF-A VEGF-A 2 7.6 The human VEGF-A gene is organized into eight exons separated by seven introns 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140301 16104843 184925 23910 12680 VEGFA VEGF-A VEGF-A 1 7.6 Human VEGF-A has at least nine subtypes due to the alternative splicing 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140302 16104843 184925 23910 12680 VEGFA VEGF VEGF 16 10.4 subtypes due to the alternative splicing of a single gene VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140303 16104843 184925 23910 12680 VEGFA VEGF VEGF 19 10.4 to the alternative splicing of a single gene VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140304 16104843 184925 23910 12680 VEGFA VEGF VEGF 22 10.4 alternative splicing of a single gene VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140305 16104843 184925 23910 12680 VEGFA VEGF VEGF 25 10.4 of a single gene VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183 VEGF 189 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140306 16104843 184925 23910 12680 VEGFA VEGF VEGF 28 10.4 single gene VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183 VEGF 189 and VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140307 16104843 184925 23910 12680 VEGFA VEGF VEGF 31 10.4 VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183 VEGF 189 and VEGF 206 13 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140308 16104843 184925 23910 12680 VEGFA VEGF VEGF 34 10.4 145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183 VEGF 189 and VEGF 206 13 14 ( Figure 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140309 16104843 184925 23910 12680 VEGFA VEGF VEGF 37 10.4 148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183 VEGF 189 and VEGF 206 13 14 ( Figure 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140310 16104843 184925 23910 12680 VEGFA VEGF VEGF 40 10.4 VEGF 165 VEGF 165 b VEGF 183 VEGF 189 and VEGF 206 13 14 ( Figure 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140311 16104843 184926 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF 165 b is an endogenous inhibitory form of VEGF which 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140312 16104843 184926 23910 12680 VEGFA VEGF VEGF 9 10.4 VEGF 165 b is an endogenous inhibitory form of VEGF which binds VEGFR-2 with the same affinity as VEGF 165 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140313 16104843 184926 10981 6307 KDR VEGFR2 VEGFR-2 12 4.3 b is an endogenous inhibitory form of VEGF which binds VEGFR-2 with the same affinity as VEGF 165 but does not 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140314 16104843 184926 23910 12680 VEGFA VEGF VEGF 18 10.4 of VEGF which binds VEGFR-2 with the same affinity as VEGF 165 but does not activate it or stimulate downstream signalling 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140315 16104843 184927 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF is produced in endothelial cells macrophages activated T-cells and a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140316 16104843 184928 23910 12680 VEGFA VEGF VEGF 7 10.4 Although virtually nothing is known about how VEGF isoform levels are regulated most VEGF-producing cells appear to preferentially 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140317 16104843 184928 23910 12680 VEGFA VEGF VEGF-producing 13 5.8 is known about how VEGF isoform levels are regulated most VEGF-producing cells appear to preferentially express VEGF 121 VEGF 165 and 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 140318 16104843 184928 23910 12680 VEGFA VEGF VEGF 19 10.4 levels are regulated most VEGF-producing cells appear to preferentially express VEGF 121 VEGF 165 and VEGF 189 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140319 16104843 184928 23910 12680 VEGFA VEGF VEGF 22 10.4 regulated most VEGF-producing cells appear to preferentially express VEGF 121 VEGF 165 and VEGF 189 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140320 16104843 184928 23910 12680 VEGFA VEGF VEGF 25 10.4 cells appear to preferentially express VEGF 121 VEGF 165 and VEGF 189 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140321 16104843 184929 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF 165 the predominant isoform is secreted as an approx 46 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140322 16104843 184930 23910 12680 VEGFA VEGF VEGF 2 10.4 In contrast VEGF 121 which lacks the residues encoded by exons 6 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140323 16104843 184931 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF 189 which contains an additional sequence encoded by exon 6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140324 16104843 184931 13346 7178 MMRN1 ECM ECM 21 0.3 6 binds heparin strongly and is completely sequestered in the ECM (extracellular extracellular matrix and to a lesser extent at the 3 JUMiner_v2.2 1 2 extracellular matrix 0 0 0 0 0 0 0 0 140325 16104843 184933 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF 165 binds the coreceptors NRP-1 (neuropilin-1) neuropilin-1 20 and NRP-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140326 16104843 184933 14682 8004 NRP1 NRP1 NRP-1 5 0.8 VEGF 165 binds the coreceptors NRP-1 (neuropilin-1) neuropilin-1 20 and NRP-2 (neuropilin-2), neuropilin-2 whereas VEGF 145 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140327 16104843 184933 14683 8005 NRP2 NRP2 NRP-2 11 0.3 VEGF 165 binds the coreceptors NRP-1 (neuropilin-1) neuropilin-1 20 and NRP-2 (neuropilin-2), neuropilin-2 whereas VEGF 145 binds only NRP-2 21 ( 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8005|NRP2|8828|Complete__7751|NELL2|4753|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 140328 16104843 184933 23910 12680 VEGFA VEGF VEGF 14 10.4 coreceptors NRP-1 (neuropilin-1) neuropilin-1 20 and NRP-2 (neuropilin-2), neuropilin-2 whereas VEGF 145 binds only NRP-2 21 ( Figure 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140329 16104843 184933 14683 8005 NRP2 NRP2 NRP-2 18 0.3 20 and NRP-2 (neuropilin-2), neuropilin-2 whereas VEGF 145 binds only NRP-2 21 ( Figure 2 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8005|NRP2|8828|Complete__7751|NELL2|4753|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 140330 16104843 184934 23910 12680 VEGFA VEGF VEGF 7 10.4 Approx 50% of mice expressing exclusively the VEGF 120 isoform (murine murine VEGF is shorter by one amino 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140331 16104843 184934 23910 12680 VEGFA VEGF VEGF 11 10.4 of mice expressing exclusively the VEGF 120 isoform (murine murine VEGF is shorter by one amino acid die within a few 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140332 16104843 184935 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF mice also exhibit a specific decrease in capillary branch formation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140333 16104843 184935 23910 12680 VEGFA VEGF VEGF 45 10.4 retinal vascular outgrowth and patterning 24 suggesting that the heparin-binding VEGF isoforms provide spatially restricted stimulatory cues to initiate vascular branch 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140334 16104843 184936 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF mice are normal and healthy and have a normal retinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140335 16104843 184936 23910 12680 VEGFA VEGF VEGF 13 10.4 normal and healthy and have a normal retinal angiogenesis whereas VEGF mice display normal venular outgrowth but impaired arterial development in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140336 16104843 184937 23910 12680 VEGFA VEGF VEGF 6 10.4 These findings suggest that the various VEGF isoforms play distinct roles in vascular patterning and arterial development 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140337 16104843 184937 23910 12680 VEGFA VEGF VEGF 19 10.4 distinct roles in vascular patterning and arterial development although the VEGF 164 isoform plays a central role in vascular development 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140338 16104843 184938 23910 12680 VEGFA VEGF VEGF 3 10.4 Gene expression of VEGF is regulated by a variety of stimuli such as hypoxia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140339 16104843 184938 22671 11998 TP53 p53 p53 17 0.3 a variety of stimuli such as hypoxia growth factors transformation p53 mutation oestrogen TSH (thyroid-stimulating thyroid-stimulating hormone tumour promoters and NO 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140340 16104843 184939 23910 12680 VEGFA VEGF VEGF 11 10.4 all of the stimuli responsible for the up-regulation of the VEGF gene are quite interesting hypoxia has been of particular interest 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140341 16104843 184940 9230 4910 HIF1A HIF-1 HIF-1 6 0.6 It is now well established that HIF-1 (hypoxia-inducible hypoxia-inducible factor-1 is a key mediator of hypoxic responses 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140342 16104843 184941 9230 4910 HIF1A HIF-1 HIF-1 0 0.6 HIF-1 is a transcriptional activator composed of HIF-1 a and HIF-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140343 16104843 184941 9230 4910 HIF1A HIF-1 HIF-1 7 0.6 HIF-1 is a transcriptional activator composed of HIF-1 a and HIF-1 b subunits 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140344 16104843 184941 9230 4910 HIF1A HIF-1 HIF-1 10 0.6 HIF-1 is a transcriptional activator composed of HIF-1 a and HIF-1 b subunits 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140345 16104843 184942 9230 4910 HIF1A HIF-1 HIF-1 1 0.6 Both HIF-1 a and HIF-1 b are constitutively expressed in various types 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140346 16104843 184942 9230 4910 HIF1A HIF-1 HIF-1 4 0.6 Both HIF-1 a and HIF-1 b are constitutively expressed in various types of tumour 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140347 16104843 184943 9230 4910 HIF1A HIF-1 HIF-1 4 0.6 Under normal oxygenation conditions HIF-1 a is scarcely detectable because it is targeted for rapid 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140348 16104843 184944 9230 4910 HIF1A HIF-1 HIF-1 10 0.6 The interaction between pVHL and a specific domain of the HIF-1 a subunit is regulated through hydroxylation of a proline residue 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140349 16104843 184944 9230 4910 HIF1A HIF-1 HIF-1 23 0.6 regulated through hydroxylation of a proline residue (Pro Pro in HIF-1 a by prolyl-4-hydroxylase which requires molecular oxygen and iron for 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140350 16104843 184945 9230 4910 HIF1A HIF-1 HIF-1 3 0.6 Under hypoxic conditions HIF-1 a expression increases as a result of suppressed prolyl hydroxylation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140351 16104843 184945 9230 4910 HIF1A HIF-1 HIF-1 15 0.6 expression increases as a result of suppressed prolyl hydroxylation of HIF-1 a and decreased ubiquitination and degradation 26 27 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140352 16104843 184946 9230 4910 HIF1A HIF-1 HIF-1 12 0.6 the oxygen-dependent hydroxylation of an asparagine residue (Asn Asn in HIF-1 a in the C-terminal transactivation domain of HIF-1 a to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140353 16104843 184946 9230 4910 HIF1A HIF-1 HIF-1 21 0.6 Asn in HIF-1 a in the C-terminal transactivation domain of HIF-1 a to promote interaction with the p300/CBP p300 CBP CREB 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140354 16104843 184946 6670 3373 EP300 p300 p300 28 1.3 domain of HIF-1 a to promote interaction with the p300/CBP p300 CBP CREB (cAMP-response-element-binding cAMP-response-element-binding protein -binding protein co-activator and induce 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140355 16104843 184946 4918 2348 CREBBP CBP CBP 28 0.6 of HIF-1 a to promote interaction with the p300/CBP p300 CBP CREB (cAMP-response-element-binding cAMP-response-element-binding protein -binding protein co-activator and induce a 1 JUMiner_v2.2 1 0 0 2 3287 TotalCon:4<>9936|OPN1LW|5956|Complete__2348|CREBBP|1387|Complete__30043|PAG1|55824|Complete__3287|EIF4E|1977|Complete__<>AvaiableGeneRif=4<>BEST:3287|EIF4E|0.000657599354192082<>ScoreDetail__9936|OPN1LW|0.000260297044862961__30043|PAG1|0.000547993778658866__3287|EIF4E|0.000657599354192082__2348|CREBBP|0.000584351253688811__ 0 0 0 0 0 140356 16104843 184946 4911 2345 CREB1 CREB CREB 29 1.6 HIF-1 a to promote interaction with the p300/CBP p300 CBP CREB (cAMP-response-element-binding cAMP-response-element-binding protein -binding protein co-activator and induce a HRE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140357 16104843 184946 23910 12680 VEGFA VEGF VEGF 44 10.4 a HRE (hypoxia hypoxia response element -driven transcription of the VEGF gene 28 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140358 16104843 184947 10826 6206 JUND JUND JunD 11 1.5 Very recently Gerald et al 29 have demonstrated that JunD a member of the AP-1 family of transcription factors is 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140359 16104843 184947 10826 6206 JUND AP-1 AP-1 16 1.5 al 29 have demonstrated that JunD a member of the AP-1 family of transcription factors is involved in the regulation of 1 JUMiner_v2.2 1 0 0 2 3797 TotalCon:5<>3796|FOS|2353|Complete__3797|FOSB|2354|Complete__6204|JUN|3725|Complete__6205|JUNB|3726|Complete__6206|JUND|3727|Complete__<>AvaiableGeneRif=5<>BEST:3797|FOSB|0.000708753020882169<>ScoreDetail__3796|FOS|0.000614177619024766__3797|FOSB|0.000708753020882169__6205|JUNB|0.000551331537078046__6204|JUN|0.00064897058248842__6206|JUND|0.000540969825441906__ 0 0 0 0 0 140360 16104843 184948 10826 6206 JUND JUND JunD 2 1.5 Deletion of JunD increases H 2 O 2 levels and thus inhibits prolyl 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140361 16104843 184949 9230 4910 HIF1A HIF-1 HIF-1 1 0.6 Consequently HIF-1 a protein accumulates under normoxic conditions and the transcription of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140362 16104843 184949 23910 12680 VEGFA VEGF-A VEGF-A 12 7.6 a protein accumulates under normoxic conditions and the transcription of VEGF-A is increased 29 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140363 16104843 184950 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF is also regulated at the level of mRNA stability 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140364 16104843 184951 23910 12680 VEGFA VEGF VEGF 8 10.4 The 5_amp_#180;- and 3_amp_#180 -UTRs (untranslated untranslated regions of the VEGF gene confer increased mRNA stability during hypoxia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140365 16104843 184952 6559 3312 ELAVL1 HuR HuR 0 0.6 HuR an AU-rich element binding protein and PAIP2 polyadenylated-binding protein-interacting protein 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 140366 16104843 184952 16010 17970 PAIP2 PAIP2 PAIP2 7 0.6 HuR an AU-rich element binding protein and PAIP2 polyadenylated-binding protein-interacting protein 2 have been identified as crucial proteins 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140367 16104843 184952 23910 12680 VEGFA VEGF VEGF 19 10.4 protein-interacting protein 2 have been identified as crucial proteins for VEGF mRNA stabilization 30 31 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140368 16104843 184953 23910 12680 VEGFA VEGF VEGF 1 10.4 Furthermore VEGF expression can be regulated at the translational level 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140369 16104843 184954 20149 10919 SLC14A2 UTR UTR 6 0.3 It has been shown that the 5_amp_#180 -UTR of VEGF mRNA contains two functional internal ribosome entry sites 11 JUMiner_v2.2 1 2 untranslated region 0 2 4468 TotalCon:2<>10919|SLC14A2|8170|Complete__4468|UTS2R|2837|Complete__<>AvaiableGeneRif=2<>BEST:4468|UTS2R|0.000718341656974755<>ScoreDetail__10919|SLC14A2|0.000381768999132343__4468|UTS2R|0.000718341656974755__ 0 0 0 0 0 140370 16104843 184954 23910 12680 VEGFA VEGF VEGF 8 10.4 It has been shown that the 5_amp_#180 -UTR of VEGF mRNA contains two functional internal ribosome entry sites that maintain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140371 16104843 184954 23910 12680 VEGFA VEGF VEGF 27 10.4 that maintain efficient cap-independent translation and ensure efficient production of VEGF even under unfavourable stress conditions such as hypoxia 32 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140372 16104843 184955 16459 8893 PGF PlGF PlGF 0 4.6 PlGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140373 16104843 184956 16459 8893 PGF PlGF PlGF 0 4.6 PlGF was originally discovered in human placenta in 1991 33 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140374 16104843 184957 16459 8893 PGF PlGF PlGF 1 4.6 The PlGF gene is highly expressed in placenta at all stages of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140375 16104843 184958 16459 8893 PGF PlGF PlGF 0 4.6 PlGF transcripts have also been detected in the heart lung thyroid 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140376 16104843 184959 16459 8893 PGF PlGF PlGF 0 4.6 PlGF binds VEGFR-1 but not VEGFR-2 35 36 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140377 16104843 184959 7629 3763 FLT1 VEGFR1 VEGFR-1 2 0.6 PlGF binds VEGFR-1 but not VEGFR-2 35 36 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140378 16104843 184959 10981 6307 KDR VEGFR2 VEGFR-2 5 4.3 PlGF binds VEGFR-1 but not VEGFR-2 35 36 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140379 16104843 184960 16459 8893 PGF PlGF PlGF 5 4.6 Alternative splicing of the human PlGF gene generates four isoforms which differ in size and binding 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140380 16104843 184960 16459 8893 PGF PlGF PlGF 18 4.6 isoforms which differ in size and binding properties PlGF-1 (PlGF PlGF 131 PlGF-2 (PlGF PlGF 152 PlGF-3 (PlGF PlGF 203 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140381 16104843 184960 16459 8893 PGF PlGF-2 PlGF-2 21 3.1 differ in size and binding properties PlGF-1 (PlGF PlGF 131 PlGF-2 (PlGF PlGF 152 PlGF-3 (PlGF PlGF 203 and PlGF-4 (PlGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140382 16104843 184960 16459 8893 PGF PlGF PlGF 22 4.6 size and binding properties PlGF-1 (PlGF PlGF 131 PlGF-2 (PlGF PlGF 152 PlGF-3 (PlGF PlGF 203 and PlGF-4 (PlGF PlGF 224 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140383 16104843 184960 16459 8893 PGF PlGF PlGF 26 4.6 PlGF-1 (PlGF PlGF 131 PlGF-2 (PlGF PlGF 152 PlGF-3 (PlGF PlGF 203 and PlGF-4 (PlGF PlGF 224 37-39 ( Figure 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140384 16104843 184960 16459 8893 PGF PlGF PlGF 31 4.6 (PlGF PlGF 152 PlGF-3 (PlGF PlGF 203 and PlGF-4 (PlGF PlGF 224 37-39 ( Figure 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140385 16104843 184962 16459 8893 PGF PlGF-2 PlGF-2 0 3.1 PlGF-2 is able to bind heparin and the co-receptors NRP-1 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140386 16104843 184962 14682 8004 NRP1 NRP1 NRP-1 9 0.8 PlGF-2 is able to bind heparin and the co-receptors NRP-1 and NRP-2 due to the insertion of a highly basic 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140387 16104843 184962 14683 8005 NRP2 NRP2 NRP-2 11 0.3 is able to bind heparin and the co-receptors NRP-1 and NRP-2 due to the insertion of a highly basic 21-amino acid 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8005|NRP2|8828|Complete__7751|NELL2|4753|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 140388 16104843 184963 16459 8893 PGF PlGF PlGF 21 4.6 72-amino acid sequence between exons 4 and 5 of the PlGF gene but lacks the coding sequence of exon 6 is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140389 16104843 184964 16459 8893 PGF PlGF-2 PlGF-2 19 3.1 a heparin-binding domain previously thought to be present only in PlGF-2 39 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140390 16104843 184965 23910 12680 VEGFA VEGF-A VEGF-A 15 7.6 PlGF-1 has shown that this protein is structurally similar to VEGF-A 40 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140391 16104843 184966 16459 8893 PGF PlGF PlGF 6 4.6 Furthermore despite this moderate sequence conservation PlGF and VEGF-A bind to the same binding interface of VEGFR-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140392 16104843 184966 23910 12680 VEGFA VEGF-A VEGF-A 8 7.6 Furthermore despite this moderate sequence conservation PlGF and VEGF-A bind to the same binding interface of VEGFR-1 in a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140393 16104843 184966 7629 3763 FLT1 VEGFR1 VEGFR-1 16 0.6 PlGF and VEGF-A bind to the same binding interface of VEGFR-1 in a very similar fashion 41 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140394 16104843 184967 23910 12680 VEGFA VEGF-A VEGF-A 8 7.6 However recent studies have reported that unlike in VEGF-A N-glycosylation in PlGF plays an important role in VEGFR-1 binding 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140395 16104843 184967 16459 8893 PGF PlGF PlGF 11 4.6 recent studies have reported that unlike in VEGF-A N-glycosylation in PlGF plays an important role in VEGFR-1 binding 42 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140396 16104843 184967 7629 3763 FLT1 VEGFR1 VEGFR-1 17 0.6 in VEGF-A N-glycosylation in PlGF plays an important role in VEGFR-1 binding 42 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140397 16104843 184968 16459 8893 PGF PlGF PlGF 12 4.6 Carmeliet et al 43 have shown that a deficiency in PlGF (PlGF PlGF does not affect embryonic angiogenesis in mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140398 16104843 184968 16459 8893 PGF PlGF PlGF 13 4.6 al 43 have shown that a deficiency in PlGF (PlGF PlGF does not affect embryonic angiogenesis in mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140399 16104843 184969 16459 8893 PGF PlGF PlGF 3 4.6 However loss of PlGF impairs angiogenesis plasma extravasation and collateral growth during ischaemia inflammation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140400 16104843 184969 7629 3763 FLT1 VEGFR1 VEGFR-1 22 0.6 ischaemia inflammation wound healing and cancer indicating the importance of VEGFR-1 signalling in pathological conditions 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140401 16104843 184970 23911 12681 VEGFB VEGFB VEGF-B 0 1.8 VEGF-B 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140402 16104843 184971 23911 12681 VEGFB VEGFB VEGF-B 0 1.8 VEGF-B has a wide tissue distribution but is particularly abundant in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140403 16104843 184972 23911 12681 VEGFB VEGFB VEGF-B 1 1.8 Human VEGF-B has two isoforms generated by alternative splicing VEGF-B 167 and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140404 16104843 184972 23911 12681 VEGFB VEGFB VEGF-B 9 1.8 Human VEGF-B has two isoforms generated by alternative splicing VEGF-B 167 and VEGF-B 186 ( Figure 1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140405 16104843 184972 23911 12681 VEGFB VEGFB VEGF-B 12 1.8 has two isoforms generated by alternative splicing VEGF-B 167 and VEGF-B 186 ( Figure 1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140406 16104843 184973 23911 12681 VEGFB VEGFB VEGF-B 1 1.8 The VEGF-B isoforms bind and activate VEGFR-1 and can also bind to 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140407 16104843 184973 7629 3763 FLT1 VEGFR1 VEGFR-1 6 0.6 The VEGF-B isoforms bind and activate VEGFR-1 and can also bind to NRP-1 44 ( Figure 2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140408 16104843 184973 14682 8004 NRP1 NRP1 NRP-1 12 0.8 isoforms bind and activate VEGFR-1 and can also bind to NRP-1 44 ( Figure 2 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140409 16104843 184974 23911 12681 VEGFB VEGFB VEGF-B 2 1.8 Studies using VEGF-B knockout (VEGF-B VEGF-B mice have yielded slightly conflicting results regarding 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140410 16104843 184974 23911 12681 VEGFB VEGFB VEGF-B 4 1.8 Studies using VEGF-B knockout (VEGF-B VEGF-B mice have yielded slightly conflicting results regarding the role of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140411 16104843 184974 23911 12681 VEGFB VEGFB VEGF-B 16 1.8 mice have yielded slightly conflicting results regarding the role of VEGF-B in angiogenesis and the development of the cardiovascular system 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140412 16104843 184975 23911 12681 VEGFB VEGFB VEGF-B 0 1.8 VEGF-B mice are viable and fertile however although Bellomo et al 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140413 16104843 184975 23911 12681 VEGFB VEGFB VEGF-B 16 1.8 and fertile however although Bellomo et al 45 demonstrated that VEGF-B mice had smaller hearts dysfunctional coronary arteries and an impaired 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140414 16104843 184975 23911 12681 VEGFB VEGFB VEGF-B 62 1.8 conduction abnormality characterized by a prolonged PQ interval and that VEGF-B was not required for proper development of the cardiovascular system 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140415 16104843 184976 23911 12681 VEGFB VEGFB VEGF-B 3 1.8 Recent studies using VEGF-B mice have demonstrated the role of VEGF-B in pathological vascular 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140416 16104843 184976 23911 12681 VEGFB VEGFB VEGF-B 10 1.8 Recent studies using VEGF-B mice have demonstrated the role of VEGF-B in pathological vascular remodelling in inflammatory arthritis 47 and protection 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140417 16104843 184977 23912 12682 VEGFC VEGFC VEGF-C 0 1.8 VEGF-C and VEGF-D 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140418 16104843 184977 7579 3708 FIGF VEGF-D VEGF-D 2 1.3 VEGF-C and VEGF-D 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140419 16104843 184978 23912 12682 VEGFC VEGFC VEGF-C 0 1.8 VEGF-C contains a region sharing approx 30% amino acid identity with 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140420 16104843 184978 23910 12680 VEGFA VEGF VEGF 11 10.4 contains a region sharing approx 30% amino acid identity with VEGF 165 however it is more closely related to VEGF-D by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140421 16104843 184978 7579 3708 FIGF VEGF-D VEGF-D 21 1.3 with VEGF 165 however it is more closely related to VEGF-D by virtue of the presence of N- and C-terminal extensions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140422 16104843 184978 23910 12680 VEGFA VEGF VEGF 38 10.4 N- and C-terminal extensions that are not found in other VEGF family members 49 ( Figure 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140423 16104843 184979 23912 12682 VEGFC VEGFC VEGF-C 1 1.8 Both VEGF-C and VEGF-D bind and activate VEGFR-3 (Flt-4; Flt-4 a member 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140424 16104843 184979 7579 3708 FIGF VEGF-D VEGF-D 3 1.3 Both VEGF-C and VEGF-D bind and activate VEGFR-3 (Flt-4; Flt-4 a member of the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140425 16104843 184979 7632 3767 FLT4 VEGFR3 VEGFR-3 7 0.6 Both VEGF-C and VEGF-D bind and activate VEGFR-3 (Flt-4; Flt-4 a member of the VEGFR family that does 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140426 16104843 184979 7632 3767 FLT4 FLT4 Flt-4 8 0.6 Both VEGF-C and VEGF-D bind and activate VEGFR-3 (Flt-4; Flt-4 a member of the VEGFR family that does not bind 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140427 16104843 184979 10981 6307 KDR VEGFR VEGFR 13 3.3 bind and activate VEGFR-3 (Flt-4; Flt-4 a member of the VEGFR family that does not bind VEGF-A as well as VEGFR-2 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140428 16104843 184979 23910 12680 VEGFA VEGF-A VEGF-A 19 7.6 a member of the VEGFR family that does not bind VEGF-A as well as VEGFR-2 and are mitogenic for cultured endothelial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140429 16104843 184979 10981 6307 KDR VEGFR2 VEGFR-2 23 4.3 VEGFR family that does not bind VEGF-A as well as VEGFR-2 and are mitogenic for cultured endothelial cells 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140430 16104843 184980 23912 12682 VEGFC VEGFC VEGF-C 0 1.8 VEGF-C also binds to NRP-2 49 ( Figure 2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140431 16104843 184980 14683 8005 NRP2 NRP2 NRP-2 4 0.3 VEGF-C also binds to NRP-2 49 ( Figure 2 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8005|NRP2|8828|Complete__7751|NELL2|4753|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 140432 16104843 184981 23912 12682 VEGFC VEGFC VEGF-C 1 1.8 Both VEGF-C and VEGF-D are produced as a preproprotein with long N- 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140433 16104843 184981 7579 3708 FIGF VEGF-D VEGF-D 3 1.3 Both VEGF-C and VEGF-D are produced as a preproprotein with long N- and C-terminal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140434 16104843 184981 23910 12680 VEGFA VEGF VEGF 17 10.4 a preproprotein with long N- and C-terminal propeptides flanking the VEGF homology domain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140435 16104843 184982 7632 3767 FLT4 VEGFR3 VEGFR-3 14 0.6 the precursor generates a form with a moderate affinity for VEGFR-3 but a second proteolytic step is required to produce the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140436 16104843 184982 10981 6307 KDR VEGFR2 VEGFR-2 34 4.3 the fully processed form with a high affinity for both VEGFR-2 and VEGFR-3 49 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140437 16104843 184982 7632 3767 FLT4 VEGFR3 VEGFR-3 36 0.6 processed form with a high affinity for both VEGFR-2 and VEGFR-3 49 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140438 16104843 184983 23912 12682 VEGFC VEGFC VEGF-C 3 1.8 This activation of VEGF-C and VEGF-D by proteolytic cleavage is at least partly regulated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140439 16104843 184983 7579 3708 FIGF VEGF-D VEGF-D 5 1.3 This activation of VEGF-C and VEGF-D by proteolytic cleavage is at least partly regulated by the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140440 16104843 184984 23912 12682 VEGFC VEGFC VEGF-C 2 1.8 Overexpression of VEGF-C in the epidermis of transgenic mice results in the development 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140441 16104843 184985 23912 12682 VEGFC VEGFC VEGF-C 3 1.8 In vitro VEGF-C and VEGF-D stimulate the migration and mitogenesis of cultured endothelial 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140442 16104843 184985 7579 3708 FIGF VEGF-D VEGF-D 5 1.3 In vitro VEGF-C and VEGF-D stimulate the migration and mitogenesis of cultured endothelial cells 49 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140443 16104843 184986 23912 12682 VEGFC VEGFC VEGF-C 4 1.8 A recent study using VEGF-C mice has demonstrated that VEGF-C is required for the initial 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140444 16104843 184986 23912 12682 VEGFC VEGFC VEGF-C 9 1.8 A recent study using VEGF-C mice has demonstrated that VEGF-C is required for the initial steps in lymphatic development and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140445 16104843 184986 23912 12682 VEGFC VEGFC VEGF-C 22 1.8 for the initial steps in lymphatic development and that both VEGF-C alleles are required for normal lymphatic development 52 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140446 16104843 184987 23912 12682 VEGFC VEGFC VEGF-C 1 1.8 Thus VEGF-C is the paracrine factor essential for lymphangiogenesis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140447 16104843 184988 7579 3708 FIGF VEGF-D VEGF-D 7 1.3 Less is known of the function of VEGF-D but Stacker et al 53 have revealed that VEGF-D induces 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140448 16104843 184988 7579 3708 FIGF VEGF-D VEGF-D 18 1.3 of VEGF-D but Stacker et al 53 have revealed that VEGF-D induces the formation of lymphatics within tumours and promotes the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140449 16104843 184990 23910 12680 VEGFA VEGF VEGF 2 10.4 Homologues of VEGF have also been identified in the genome of the parapoxvirus 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140450 16104843 184990 1860 18380 BZW1 ORF Orf 13 0.3 have also been identified in the genome of the parapoxvirus Orf virus 54 and have been shown to have VEGF-A-like activities 2 JUMiner_v2.2 1 2 orf 0 2 18380 TotalCon:2<>18380|BZW1|9689|Complete__11866|TMEFF1|8577|Complete__<>AvaiableGeneRif=2<>BEST:18380|BZW1|0.000784719032307457<>ScoreDetail__18380|BZW1|0.000784719032307457__11866|TMEFF1|0.000674666972898484__ 0 0 0 0 0 140451 16104843 184990 23910 12680 VEGFA VEGF-A VEGF-A-like 24 5.8 parapoxvirus Orf virus 54 and have been shown to have VEGF-A-like activities 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140452 16104843 184991 23910 12680 VEGFA VEGF VEGF 14 10.4 for a group of these proteins including VEGF-E NZ-2 (VEGF VEGF from Orf virus strain NZ-2 55 VEGF-E NZ-7 (VEGF VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140453 16104843 184991 1860 18380 BZW1 ORF Orf 16 0.3 group of these proteins including VEGF-E NZ-2 (VEGF VEGF from Orf virus strain NZ-2 55 VEGF-E NZ-7 (VEGF VEGF from Orf 2 JUMiner_v2.2 1 2 orf 0 2 18380 TotalCon:2<>18380|BZW1|9689|Complete__11866|TMEFF1|8577|Complete__<>AvaiableGeneRif=2<>BEST:18380|BZW1|0.000784719032307457<>ScoreDetail__18380|BZW1|0.000784719032307457__11866|TMEFF1|0.000674666972898484__ 0 0 0 0 0 140454 16104843 184991 23910 12680 VEGFA VEGF VEGF 25 10.4 VEGF from Orf virus strain NZ-2 55 VEGF-E NZ-7 (VEGF VEGF from Orf virus strain NZ-7 56 VEGF-E NZ-10 (VEGF VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140455 16104843 184991 1860 18380 BZW1 ORF Orf 27 0.3 Orf virus strain NZ-2 55 VEGF-E NZ-7 (VEGF VEGF from Orf virus strain NZ-7 56 VEGF-E NZ-10 (VEGF VEGF from Orf 2 JUMiner_v2.2 1 2 orf 0 2 18380 TotalCon:2<>18380|BZW1|9689|Complete__11866|TMEFF1|8577|Complete__<>AvaiableGeneRif=2<>BEST:18380|BZW1|0.000784719032307457<>ScoreDetail__18380|BZW1|0.000784719032307457__11866|TMEFF1|0.000674666972898484__ 0 0 0 0 0 140456 16104843 184991 23910 12680 VEGFA VEGF VEGF 36 10.4 VEGF from Orf virus strain NZ-7 56 VEGF-E NZ-10 (VEGF VEGF from Orf virus strain NZ-10 57 VEGF-E D1701 (VEGF VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140457 16104843 184991 1860 18380 BZW1 ORF Orf 38 0.3 Orf virus strain NZ-7 56 VEGF-E NZ-10 (VEGF VEGF from Orf virus strain NZ-10 57 VEGF-E D1701 (VEGF VEGF from Orf 2 JUMiner_v2.2 1 2 orf 0 2 18380 TotalCon:2<>18380|BZW1|9689|Complete__11866|TMEFF1|8577|Complete__<>AvaiableGeneRif=2<>BEST:18380|BZW1|0.000784719032307457<>ScoreDetail__18380|BZW1|0.000784719032307457__11866|TMEFF1|0.000674666972898484__ 0 0 0 0 0 140458 16104843 184991 23910 12680 VEGFA VEGF VEGF 47 10.4 VEGF from Orf virus strain NZ-10 57 VEGF-E D1701 (VEGF VEGF from Orf virus strain D1701 58 and VEGF-E VR634 (VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140459 16104843 184991 1860 18380 BZW1 ORF Orf 49 0.3 Orf virus strain NZ-10 57 VEGF-E D1701 (VEGF VEGF from Orf virus strain D1701 58 and VEGF-E VR634 (VEGF VEGF from 2 JUMiner_v2.2 1 2 orf 0 2 18380 TotalCon:2<>18380|BZW1|9689|Complete__11866|TMEFF1|8577|Complete__<>AvaiableGeneRif=2<>BEST:18380|BZW1|0.000784719032307457<>ScoreDetail__18380|BZW1|0.000784719032307457__11866|TMEFF1|0.000674666972898484__ 0 0 0 0 0 140460 16104843 184991 23910 12680 VEGFA VEGF VEGF 59 10.4 from Orf virus strain D1701 58 and VEGF-E VR634 (VEGF VEGF from Pseudocowpox virus strain VR634 57 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140461 16104843 184992 10981 6307 KDR VEGFR2 VEGFR-2 7 4.3 All VEGF-E variants studied bind and activate VEGFR-2 but not VEGFR-1 or VEGFR-3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140462 16104843 184992 7629 3763 FLT1 VEGFR1 VEGFR-1 10 0.6 All VEGF-E variants studied bind and activate VEGFR-2 but not VEGFR-1 or VEGFR-3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140463 16104843 184992 7632 3767 FLT4 VEGFR3 VEGFR-3 12 0.6 variants studied bind and activate VEGFR-2 but not VEGFR-1 or VEGFR-3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140464 16104843 184993 14682 8004 NRP1 NRP1 NRP-1 10 0.8 VEGF-E NZ-2 VEGF-E NZ-10 and VEGF-E D1701 can bind NRP-1 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140465 16104843 184994 14682 8004 NRP1 NRP1 NRP-1 11 0.8 VEGF-E NZ-7 and VEGF-E VR634 however are unable to bind NRP-1 ( Figure 2 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140466 16104843 184995 23910 12680 VEGFA VEGF VEGF 7 10.4 VEGF-E seems to be as potent as VEGF 165 at stimulating endothelial cell proliferation despite lacking a heparin-binding 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140467 16104843 184996 11376 6416 KRT14 K14 K14-driven 0 0.0 K14-driven VEGF-E NZ-7 transgenic mice have shown a significant increase in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140468 16104843 184998 23910 12680 VEGFA VEGF VEGF 1 10.4 Recently VEGF family proteins have been identified in snake venom including svVEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140469 16104843 184999 23910 12680 VEGFA VEGF VEGFs 13 5.8 et al 61 have shown that snakes utilize these venom-specific VEGFs in addition to VEGF-A svVEGFs function as dimers and each 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140470 16104843 184999 23910 12680 VEGFA VEGF-A VEGF-A 17 7.6 shown that snakes utilize these venom-specific VEGFs in addition to VEGF-A svVEGFs function as dimers and each chain comprises approx 110-122 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140471 16104843 185000 23910 12680 VEGFA VEGF VEGF 8 10.4 The cysteine knot motif a characteristic of the VEGF family of proteins is completely conserved in svVEGFs and the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140472 16104843 185000 23910 12680 VEGFA VEGF VEGF 23 10.4 completely conserved in svVEGFs and the sequence identity with human VEGF 165 is approx 50% ( Figure 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140473 16104843 185001 7629 3763 FLT1 VEGFR1 VEGFR-1 4 0.6 Vammin does not bind VEGFR-1 but binds VEGFR-2 with high affinity as well as VEGF 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140474 16104843 185001 10981 6307 KDR VEGFR2 VEGFR-2 7 4.3 Vammin does not bind VEGFR-1 but binds VEGFR-2 with high affinity as well as VEGF 165 64 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140475 16104843 185001 23910 12680 VEGFA VEGF VEGF 14 10.4 VEGFR-1 but binds VEGFR-2 with high affinity as well as VEGF 165 64 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140476 16104843 185002 7629 3763 FLT1 VEGFR1 VEGFR-1 4 0.6 However Tf svVEGF binds VEGFR-1 with high affinity and VEGFR-2 with low affinity compared with 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140477 16104843 185002 10981 6307 KDR VEGFR2 VEGFR-2 9 4.3 However Tf svVEGF binds VEGFR-1 with high affinity and VEGFR-2 with low affinity compared with VEGF 165 leading to a 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140478 16104843 185002 23910 12680 VEGFA VEGF VEGF 15 10.4 with high affinity and VEGFR-2 with low affinity compared with VEGF 165 leading to a strong enhancement of vascular permeability but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140479 16104843 185003 7632 3767 FLT4 VEGFR3 VEGFR-3 9 0.6 Both vammin and Tf svVEGF are unable to bind VEGFR-3 or NRP-1 but Tf svVEGF binds heparin svVEGFs may contribute 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140480 16104843 185003 14682 8004 NRP1 NRP1 NRP-1 11 0.8 vammin and Tf svVEGF are unable to bind VEGFR-3 or NRP-1 but Tf svVEGF binds heparin svVEGFs may contribute to the 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140481 16104843 185004 10981 6307 KDR VEGFR VEGFRs 0 3.0 VEGFRs 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140482 16104843 185005 7629 3763 FLT1 VEGFR1 VEGFR-1 0 0.6 VEGFR-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140483 16104843 185006 7629 3763 FLT1 VEGFR1 VEGFR-1 0 0.6 VEGFR-1 is a 180 kDa high-affinity receptor for VEGF-A VEGF-B PlGF 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140484 16104843 185006 23910 12680 VEGFA VEGF-A VEGF-A 8 7.6 VEGFR-1 is a 180 kDa high-affinity receptor for VEGF-A VEGF-B PlGF and Tf svVEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140485 16104843 185006 23911 12681 VEGFB VEGFB VEGF-B 9 1.8 VEGFR-1 is a 180 kDa high-affinity receptor for VEGF-A VEGF-B PlGF and Tf svVEGF 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140486 16104843 185006 16459 8893 PGF PlGF PlGF 10 4.6 VEGFR-1 is a 180 kDa high-affinity receptor for VEGF-A VEGF-B PlGF and Tf svVEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140487 16104843 185008 7629 3763 FLT1 VEGFR1 VEGFR-1 5 0.6 The second Ig domain of VEGFR-1 is the major binding site for VEGF-A and PlGF 16 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140488 16104843 185008 23910 12680 VEGFA VEGF-A VEGF-A 12 7.6 Ig domain of VEGFR-1 is the major binding site for VEGF-A and PlGF 16 41 67 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140489 16104843 185008 16459 8893 PGF PlGF PlGF 14 4.6 of VEGFR-1 is the major binding site for VEGF-A and PlGF 16 41 67 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140490 16104843 185009 7629 3763 FLT1 VEGFR1 VEGFR-1 0 0.6 VEGFR-1 binds VEGF-A with at least 10-fold higher affinity than VEGFR-2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140491 16104843 185009 23910 12680 VEGFA VEGF-A VEGF-A 2 7.6 VEGFR-1 binds VEGF-A with at least 10-fold higher affinity than VEGFR-2 ( K 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140492 16104843 185009 10981 6307 KDR VEGFR2 VEGFR-2 10 4.3 VEGFR-1 binds VEGF-A with at least 10-fold higher affinity than VEGFR-2 ( K d =10-30 pM 16 however ligand binding results 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140493 16104843 185010 10981 6307 KDR VEGFR2 VEGFR-2 6 4.3 In many cases the effects of VEGFR-2 on endothelial cells such as those on cell survival and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140494 16104843 185011 7629 3763 FLT1 VEGFR1 VEGFR-1 0 0.6 VEGFR-1 is a negative regulator of angiogenesis during early development but 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140495 16104843 185012 10981 6307 KDR VEGFR VEGFR-1-blocking 0 3.0 VEGFR-1-blocking antibodies prevent the migration but not proliferation of HUVECs (human 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140496 16104843 185012 23910 12680 VEGFA VEGF-A VEGF-A 18 7.6 HUVECs (human human umbilical vein endothelial cells in response to VEGF-A indicating the involvement of VEGFR-1 in endothelial cell migration 68 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140497 16104843 185012 7629 3763 FLT1 VEGFR1 VEGFR-1 23 0.6 endothelial cells in response to VEGF-A indicating the involvement of VEGFR-1 in endothelial cell migration 68 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140498 16104843 185013 12337 6871 MAPK1 p38 p38 11 2.2 signalling appears to preferentially modulate the reorganization of actin via p38 MAPK (mitogen-activated mitogen-activated protein kinase whereas VEGFR-2 contributes to the 1 JUMiner_v2.2 1 0 0 2 6878 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6878|MAPK4|0.000820263796837063<>ScoreDetail__1189|AHSA1|0.00033685499923442__6878|MAPK4|0.000820263796837063__6871|MAPK1|0.000783615282658543__6876|MAPK14|0.000706125935182395__ 0 0 0 0 0 140499 16104843 185013 12337 6871 MAPK1 MAPK MAPK 12 2.2 appears to preferentially modulate the reorganization of actin via p38 MAPK (mitogen-activated mitogen-activated protein kinase whereas VEGFR-2 contributes to the re-organization 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140500 16104843 185013 10981 6307 KDR VEGFR2 VEGFR-2 17 4.3 of actin via p38 MAPK (mitogen-activated mitogen-activated protein kinase whereas VEGFR-2 contributes to the re-organization of the cytoskeleton by phosphorylating FAK 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140501 16104843 185013 17616 9611 PTK2 FAK FAK 27 0.3 VEGFR-2 contributes to the re-organization of the cytoskeleton by phosphorylating FAK (focal focal adhesion kinase and paxillin ( Figure 2 suggesting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140502 16104843 185014 7629 3763 FLT1 VEGFR1 VEGFR-1 0 0.6 VEGFR-1 signalling is also involved in the migration of monocytes/macrophages monocytes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140503 16104843 185015 7629 3763 FLT1 VEGFR1 VEGFR-1 5 0.6 An alternatively spliced form of VEGFR-1 that encodes a soluble truncated form of the receptor containing 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140504 16104843 185015 7629 3763 FLT1 VEGFR1 VEGFR-1 35 0.6 cloned from a HUVEC cDNA library 16 sVEGFR-1 (soluble soluble VEGFR-1 inhibits VEGF-A activity by sequestering VEGF-A from signalling receptors and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140505 16104843 185015 23910 12680 VEGFA VEGF-A VEGF-A 37 7.6 a HUVEC cDNA library 16 sVEGFR-1 (soluble soluble VEGFR-1 inhibits VEGF-A activity by sequestering VEGF-A from signalling receptors and by forming 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140506 16104843 185015 23910 12680 VEGFA VEGF-A VEGF-A 41 7.6 16 sVEGFR-1 (soluble soluble VEGFR-1 inhibits VEGF-A activity by sequestering VEGF-A from signalling receptors and by forming non-signalling heterodimers with VEGFR-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140507 16104843 185015 10981 6307 KDR VEGFR2 VEGFR-2 51 4.3 VEGF-A from signalling receptors and by forming non-signalling heterodimers with VEGFR-2 69 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140508 16104843 185018 23910 12680 VEGFA VEGF VEGF 17 10.4 with pre-eclampsia are associated with decreased circulating levels of free VEGF and PlGF resulting in general endothelial dysfunction 73 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140509 16104843 185018 16459 8893 PGF PlGF PlGF 19 4.6 are associated with decreased circulating levels of free VEGF and PlGF resulting in general endothelial dysfunction 73 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140510 16104843 185019 10981 6307 KDR VEGFR2 VEGFR-2 0 4.3 VEGFR-2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140511 16104843 185020 10981 6307 KDR VEGFR2 VEGFR-2 0 4.3 VEGFR-2 is a 200-230 kDa high-affinity receptor for VEGF-A ( K 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140512 16104843 185020 23910 12680 VEGFA VEGF-A VEGF-A 8 7.6 VEGFR-2 is a 200-230 kDa high-affinity receptor for VEGF-A ( K d =75-760 pM VEGF-E and svVEGFs as well 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140513 16104843 185020 23912 12682 VEGFC VEGFC VEGF-C 24 1.8 VEGF-E and svVEGFs as well as the processed form of VEGF-C and VEGF-D 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140514 16104843 185020 7579 3708 FIGF VEGF-D VEGF-D 26 1.3 svVEGFs as well as the processed form of VEGF-C and VEGF-D 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140515 16104843 185021 23910 12680 VEGFA VEGF-A VEGF-A 4 7.6 The binding site for VEGF-A has been mapped to the second and third Ig domains 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140516 16104843 185022 10981 6307 KDR VEGFR2 VEGFR-2 0 4.3 VEGFR-2 is expressed in vascular and lymphatic endothelial cells and other 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140517 16104843 185023 10981 6307 KDR VEGFR2 VEGFR-2 5 4.3 Tyrosine phosphorylation sites in human VEGFR-2 bound to VEGF-A are Tyr and Tyr in the kinase-insert 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140518 16104843 185023 23910 12680 VEGFA VEGF-A VEGF-A 8 7.6 Tyrosine phosphorylation sites in human VEGFR-2 bound to VEGF-A are Tyr and Tyr in the kinase-insert domain Tyr and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140519 16104843 185024 23910 12680 VEGFA VEGF-A VEGF-A-dependent 9 5.8 Among them Tyr and Tyr are the two major VEGF-A-dependent autophosphorylation sites 76 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140520 16104843 185025 10981 6307 KDR VEGFR VEGFR-associated 7 3.5 Tyr creates a binding site for the VEGFR-associated protein 77 and Tyr creates a binding site for Sck 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140521 16104843 185025 19900 29869 SHC2 SCK Sck 19 0.6 VEGFR-associated protein 77 and Tyr creates a binding site for Sck 78 Shb 79 and PLC (phospholipase phospholipase C -g 76 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140522 16104843 185025 19896 10838 SHB SHB Shb 23 0.6 77 and Tyr creates a binding site for Sck 78 Shb 79 and PLC (phospholipase phospholipase C -g 76 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140523 16104843 185025 16745 9065 PLCG1 PLC PLC 28 0.9 creates a binding site for Sck 78 Shb 79 and PLC (phospholipase phospholipase C -g 76 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140524 16104843 185026 10981 6307 KDR VEGFR2 VEGFR-2 0 4.3 VEGFR-2 is the major mediator of the mitogenic angiogenic and permeability-enhancing 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140525 16104843 185026 23910 12680 VEGFA VEGF-A VEGF-A 13 7.6 major mediator of the mitogenic angiogenic and permeability-enhancing effects of VEGF-A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140526 16104843 185027 10981 6307 KDR VEGFR2 VEGFR-2 9 4.3 Furthermore recent studies have indicated that the activation of VEGFR-2 also promotes lymphangiogenesis 80 81 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140527 16104843 185028 10981 6307 KDR VEGFR2 VEGFR-2 6 4.3 Survival signalling for endothelial cells from VEGFR-2 is reported to involve the PI3K (phosphoinositide phosphoinositide 3-kinase)/Akt 3-kinase 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140528 16104843 185028 16613 8975 PIK3CA PI3K PI3K 12 1.0 for endothelial cells from VEGFR-2 is reported to involve the PI3K (phosphoinositide phosphoinositide 3-kinase)/Akt 3-kinase Akt pathway 82 83 ( Figure 1 JUMiner_v2.2 1 0 0 2 8978 TotalCon:3<>8975|PIK3CA|5290|Complete__8976|PIK3CB|5291|Complete__8978|PIK3CG|5294|Complete__<>AvaiableGeneRif=3<>BEST:8978|PIK3CG|0.00206242925388024<>ScoreDetail__8976|PIK3CB|0.00117343649258543__8978|PIK3CG|0.00206242925388024__8975|PIK3CA|0.0010350674023782__ 0 0 0 0 0 140529 16104843 185028 543 391 AKT1 AKT Akt 14 0.3 is reported to involve the PI3K (phosphoinositide phosphoinositide 3-kinase)/Akt 3-kinase Akt pathway 82 83 ( Figure 2 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140530 16104843 185029 16613 8975 PIK3CA PI3K PI3K 11 1.0 another pathway may be involved since the signal to activate PI3K by VEGFR-2 is usually not very strong 1 JUMiner_v2.2 1 0 0 2 8978 TotalCon:3<>8975|PIK3CA|5290|Complete__8976|PIK3CB|5291|Complete__8978|PIK3CG|5294|Complete__<>AvaiableGeneRif=3<>BEST:8978|PIK3CG|0.00206242925388024<>ScoreDetail__8976|PIK3CB|0.00117343649258543__8978|PIK3CG|0.00206242925388024__8975|PIK3CA|0.0010350674023782__ 0 0 0 0 0 140531 16104843 185029 10981 6307 KDR VEGFR2 VEGFR-2 13 4.3 may be involved since the signal to activate PI3K by VEGFR-2 is usually not very strong 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140532 16104843 185030 10981 6307 KDR VEGFR2 VEGFR-2 12 4.3 Byzova et al 84 have reported that the activation of VEGFR-2 by VEGF-A results in the PI3K/Akt-dependent PI3K Akt-dependent activation of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140533 16104843 185030 23910 12680 VEGFA VEGF-A VEGF-A 14 7.6 al 84 have reported that the activation of VEGFR-2 by VEGF-A results in the PI3K/Akt-dependent PI3K Akt-dependent activation of several integrins 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140534 16104843 185030 16613 8975 PIK3CA PI3K PI3K 18 1.0 the activation of VEGFR-2 by VEGF-A results in the PI3K/Akt-dependent PI3K Akt-dependent activation of several integrins leading to enhanced cell adhesion 1 JUMiner_v2.2 1 0 0 2 8978 TotalCon:3<>8975|PIK3CA|5290|Complete__8976|PIK3CB|5291|Complete__8978|PIK3CG|5294|Complete__<>AvaiableGeneRif=3<>BEST:8978|PIK3CG|0.00206242925388024<>ScoreDetail__8976|PIK3CB|0.00117343649258543__8978|PIK3CG|0.00206242925388024__8975|PIK3CA|0.0010350674023782__ 0 0 0 0 0 140535 16104843 185031 10981 6307 KDR VEGFR2 VEGFR-2 11 4.3 synergic interaction with integrins is required for productive signalling from VEGFR-2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140536 16104843 185032 10981 6307 KDR VEGFR2 VEGFR-2 9 4.3 Very recently a naturally occurring soluble truncated form of VEGFR-2 has been detected in mouse and human plasma 85 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140537 16104843 185033 10981 6307 KDR VEGFR2 VEGFR-2 5 4.3 Similar to sVEGFR-1 sVEGFR-2 (soluble soluble VEGFR-2 may have regulatory consequences with respect to VEGF-mediated angiogenesis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140538 16104843 185033 23910 12680 VEGFA VEGF VEGF-mediated 13 5.8 (soluble soluble VEGFR-2 may have regulatory consequences with respect to VEGF-mediated angiogenesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140539 16104843 185034 7632 3767 FLT4 VEGFR3 VEGFR-3 0 0.6 VEGFR-3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140540 16104843 185035 7632 3767 FLT4 VEGFR3 VEGFR-3 0 0.6 VEGFR-3 is a 195 kDa high-affinity receptor for VEGF-C and VEGF-D 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140541 16104843 185035 23912 12682 VEGFC VEGFC VEGF-C 8 1.8 VEGFR-3 is a 195 kDa high-affinity receptor for VEGF-C and VEGF-D 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140542 16104843 185035 7579 3708 FIGF VEGF-D VEGF-D 10 1.3 VEGFR-3 is a 195 kDa high-affinity receptor for VEGF-C and VEGF-D 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140543 16104843 185036 7629 3763 FLT1 VEGFR1 VEGFR-1 1 0.6 Unlike VEGFR-1 and VEGFR-2 VEGFR-3 is proteolytically cleaved within the fifth extracellular 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140544 16104843 185036 10981 6307 KDR VEGFR2 VEGFR-2 3 4.3 Unlike VEGFR-1 and VEGFR-2 VEGFR-3 is proteolytically cleaved within the fifth extracellular Ig loop 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140545 16104843 185036 7632 3767 FLT4 VEGFR3 VEGFR-3 4 0.6 Unlike VEGFR-1 and VEGFR-2 VEGFR-3 is proteolytically cleaved within the fifth extracellular Ig loop into 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140546 16104843 185037 7632 3767 FLT4 VEGFR3 VEGFR-3 4 0.6 Overexpression of a soluble VEGFR-3 in the skin of mice inhibits fetal lymphangiogenesis and induces 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140547 16104843 185038 23912 12682 VEGFC VEGFC VEGF-C 7 1.8 Furthermore overexpression of a VEGFR-3-specific mutant of VEGF-C (VEGF-C VEGF-C 156S in the skin induces the growth of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140548 16104843 185038 23912 12682 VEGFC VEGFC VEGF-C 8 1.8 Furthermore overexpression of a VEGFR-3-specific mutant of VEGF-C (VEGF-C VEGF-C 156S in the skin induces the growth of lymphatic vessels 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140549 16104843 185038 7632 3767 FLT4 VEGFR3 VEGFR-3 34 0.6 on the blood vessel architecture 87 indicating that stimulation of VEGFR-3 alone is sufficient to induce lymphangiogenesis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140550 16104843 185039 7632 3767 FLT4 VEGFR3 VEGFR-3 3 0.6 The stimulation of VEGFR-3 also protects the lymphatic endothelial cells from serum deprivation-induced apoptosis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140551 16104843 185040 7632 3767 FLT4 VEGFR3 VEGFR-3 3 0.6 The phosphorylation of VEGFR-3 has been shown to lead to a PI3K-dependent activation of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140552 16104843 185040 16613 8975 PIK3CA PI3K PI3K-dependent 11 1.0 phosphorylation of VEGFR-3 has been shown to lead to a PI3K-dependent activation of Akt and PKC (protein protein kinase C -dependent 1 JUMiner_v2.2 1 0 0 2 8978 TotalCon:3<>8975|PIK3CA|5290|Complete__8976|PIK3CB|5291|Complete__8978|PIK3CG|5294|Complete__<>AvaiableGeneRif=3<>BEST:8978|PIK3CG|0.00206242925388024<>ScoreDetail__8976|PIK3CB|0.00117343649258543__8978|PIK3CG|0.00206242925388024__8975|PIK3CA|0.0010350674023782__ 0 0 0 0 0 140553 16104843 185040 543 391 AKT1 AKT Akt 14 0.3 has been shown to lead to a PI3K-dependent activation of Akt and PKC (protein protein kinase C -dependent activation of p42/p44 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140554 16104843 185040 3833 21420 CCRK p42 p42 22 0.3 and PKC (protein protein kinase C -dependent activation of p42/p44 p42 p44 MAPK 88 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:4<>21420|CCRK|23552|Complete__9553|PSMC6|5706|No_GeneRif__1781|CDKL1|8814|No_GeneRif__21182|NUP43|348995|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 140555 16104843 185040 12337 6871 MAPK1 MAPK MAPK 23 2.2 (protein protein kinase C -dependent activation of p42/p44 p42 p44 MAPK 88 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140556 16104843 185040 9869 16938 IFI44 p44 p44 22 0.5 PKC (protein protein kinase C -dependent activation of p42/p44 p42 p44 MAPK 88 4 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140557 16104843 185041 7632 3767 FLT4 VEGFR3 VEGFR-3 11 0.6 A recent study 89 has demonstrated that blockade of VEGFR-3 signalling significantly suppresses corneal dendritic cell trafficking to draining lymph 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140558 16104843 185041 7632 3767 FLT4 VEGFR3 VEGFR-3 40 0.6 hypersensitivity and rejection of corneal transplants suggesting a role for VEGFR-3 in adaptive immunity 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140559 16104843 185042 14682 8004 NRP1 NRP1 NRP-1 0 0.8 NRP-1 and NRP-2 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140560 16104843 185042 14683 8005 NRP2 NRP2 NRP-2 2 0.3 NRP-1 and NRP-2 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8005|NRP2|8828|Complete__7751|NELL2|4753|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 140561 16104843 185043 14682 8004 NRP1 NRP1 NRP-1 0 0.8 NRP-1 is a 130-140 kDa cell-surface glycoprotein first identified as a 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140562 16104843 185043 23910 12680 VEGFA VEGF-A VEGF-A 28 7.6 guidance 90 and subsequently found as an isoform-specific receptor for VEGF-A 20 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140563 16104843 185044 14683 8005 NRP2 NRP2 NRP-2 0 0.3 NRP-2 was identified by virtue of its sequence homology with NRP-1 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8005|NRP2|8828|Complete__7751|NELL2|4753|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 140564 16104843 185044 14682 8004 NRP1 NRP1 NRP-1 10 0.8 NRP-2 was identified by virtue of its sequence homology with NRP-1 and shares 44% identity at the amino acid level with 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140565 16104843 185044 14682 8004 NRP1 NRP1 NRP-1 21 0.8 and shares 44% identity at the amino acid level with NRP-1 90 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140566 16104843 185045 14682 8004 NRP1 NRP1 NRP-1 0 0.8 NRP-1 is able to bind VEGF 165 VEGF-B PlGF-2 and some 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140567 16104843 185045 23910 12680 VEGFA VEGF VEGF 5 10.4 NRP-1 is able to bind VEGF 165 VEGF-B PlGF-2 and some VEGF-E variants whereas NRP-2 can 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140568 16104843 185045 23911 12681 VEGFB VEGFB VEGF-B 8 1.8 NRP-1 is able to bind VEGF 165 VEGF-B PlGF-2 and some VEGF-E variants whereas NRP-2 can bind VEGF 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140569 16104843 185045 16459 8893 PGF PlGF-2 PlGF-2 9 3.1 NRP-1 is able to bind VEGF 165 VEGF-B PlGF-2 and some VEGF-E variants whereas NRP-2 can bind VEGF 145 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140570 16104843 185045 14683 8005 NRP2 NRP2 NRP-2 15 0.3 bind VEGF 165 VEGF-B PlGF-2 and some VEGF-E variants whereas NRP-2 can bind VEGF 145 VEGF 165 PlGF-2 and VEGF-C 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8005|NRP2|8828|Complete__7751|NELL2|4753|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 140571 16104843 185045 23910 12680 VEGFA VEGF VEGF 18 10.4 VEGF-B PlGF-2 and some VEGF-E variants whereas NRP-2 can bind VEGF 145 VEGF 165 PlGF-2 and VEGF-C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140572 16104843 185045 23910 12680 VEGFA VEGF VEGF 21 10.4 and some VEGF-E variants whereas NRP-2 can bind VEGF 145 VEGF 165 PlGF-2 and VEGF-C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140573 16104843 185045 16459 8893 PGF PlGF-2 PlGF-2 24 3.1 VEGF-E variants whereas NRP-2 can bind VEGF 145 VEGF 165 PlGF-2 and VEGF-C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140574 16104843 185045 23912 12682 VEGFC VEGFC VEGF-C 26 1.8 whereas NRP-2 can bind VEGF 145 VEGF 165 PlGF-2 and VEGF-C 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140575 16104843 185046 14682 8004 NRP1 NRP NRPs 4 0.8 The intracellular domains of NRPs are short and do not suffice for the independent transduction 13 JUMiner_v2.2 1 0 0 2 8004 TotalCon:3<>7637|NAP1L1|4673|Complete__8004|NRP1|8829|Complete__17142|OPTN|10133|Complete__<>AvaiableGeneRif=3<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__7637|NAP1L1|0.000712684957057947__8004|NRP1|0.00122944631586111__17142|OPTN|0.000391130231927032__ 0 0 0 0 0 140576 16104843 185046 23910 12680 VEGFA VEGF VEGF 22 10.4 the independent transduction of biological signals subsequent to semaphorin or VEGF binding 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140577 16104843 185047 14682 8004 NRP1 NRP NRPs 6 0.8 It has been shown that both NRPs can join with receptors belonging to the plexin family and 13 JUMiner_v2.2 1 0 0 2 8004 TotalCon:3<>7637|NAP1L1|4673|Complete__8004|NRP1|8829|Complete__17142|OPTN|10133|Complete__<>AvaiableGeneRif=3<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__7637|NAP1L1|0.000712684957057947__8004|NRP1|0.00122944631586111__17142|OPTN|0.000391130231927032__ 0 0 0 0 0 140578 16104843 185047 14682 8004 NRP1 NRP NRP 18 0.8 receptors belonging to the plexin family and such plexin/NRP plexin NRP complexes are able to transduce signals as the physiological receptor 13 JUMiner_v2.2 1 0 0 2 8004 TotalCon:3<>7637|NAP1L1|4673|Complete__8004|NRP1|8829|Complete__17142|OPTN|10133|Complete__<>AvaiableGeneRif=3<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__7637|NAP1L1|0.000712684957057947__8004|NRP1|0.00122944631586111__17142|OPTN|0.000391130231927032__ 0 0 0 0 0 140579 16104843 185048 23910 12680 VEGFA VEGF VEGF 1 10.4 The VEGF 165 -induced proliferation and migration of cells that express VEGFR-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140580 16104843 185048 10981 6307 KDR VEGFR2 VEGFR-2 11 4.3 VEGF 165 -induced proliferation and migration of cells that express VEGFR-2 are enhanced in the presence of NRP-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140581 16104843 185048 14682 8004 NRP1 NRP1 NRP-1 18 0.8 cells that express VEGFR-2 are enhanced in the presence of NRP-1 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140582 16104843 185049 14682 8004 NRP1 NRP1 NRP-1 1 0.8 Thus NRP-1 also seems to function as an enhancer of VEGFR-2 activity 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140583 16104843 185049 10981 6307 KDR VEGFR2 VEGFR-2 10 4.3 Thus NRP-1 also seems to function as an enhancer of VEGFR-2 activity in the presence of VEGF 165 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140584 16104843 185049 23910 12680 VEGFA VEGF VEGF 16 10.4 as an enhancer of VEGFR-2 activity in the presence of VEGF 165 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140585 16104843 185050 10981 6307 KDR VEGFR2 VEGFR-2 17 4.3 is the result of the formation of a complex between VEGFR-2 and NRP-1 93 94 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140586 16104843 185050 14682 8004 NRP1 NRP1 NRP-1 19 0.8 result of the formation of a complex between VEGFR-2 and NRP-1 93 94 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140587 16104843 185051 14682 8004 NRP1 NRP1 NRP-1 10 0.8 An in vivo study with transgenic mice has shown that NRP-1 is important not only for neuronal development but also for 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140588 16104843 185052 14682 8004 NRP1 NRP1 NRP-1 0 0.8 NRP-1 mice suffer from severe defects in the cardiovascular system in 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140589 16104843 185053 14682 8004 NRP1 NRP1 NRP-1 28 0.8 aortic arches and the yolk-sac vasculature suggesting the importance of NRP-1 in embryonic vessel formation 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140590 16104843 185054 14683 8005 NRP2 NRP2 NRP-2 2 0.3 In contrast NRP-2 mice show an absence or severe reduction of small lymphatic 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8005|NRP2|8828|Complete__7751|NELL2|4753|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 140591 16104843 185055 14683 8005 NRP2 NRP2 NRP-2 11 0.3 veins and larger collecting lymphatic vessels develop normally suggesting that NRP-2 is selectively required for the formation of small lymphatic vessels 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8005|NRP2|8828|Complete__7751|NELL2|4753|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 140592 16104843 185056 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF/VEGFR VEGF VEGFR SYSTEM IN PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140593 16104843 185056 10981 6307 KDR VEGFR VEGFR 0 3.3 VEGF/VEGFR VEGF VEGFR SYSTEM IN PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140594 16104843 185058 23910 12680 VEGFA VEGF VEGF 5 10.4 The loss of a single VEGF allele is lethal in the mouse embryo between days 11 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140595 16104843 185059 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF embryos exhibit significant defects in the vasculature of several organs 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140596 16104843 185060 23910 12680 VEGFA VEGF-A VEGF-A 8 7.6 In addition a 2- to 3-fold overexpression of VEGF-A from its endogenous locus results in severe abnormalities in heart 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140597 16104843 185061 23910 12680 VEGFA VEGF-A VEGF-A 8 7.6 These results demonstrate the importance of tightly regulating VEGF-A expression during embryonic development 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140598 16104843 185062 7629 3763 FLT1 VEGFR1 VEGFR-1 4 0.6 Homozygous loss of the VEGFR-1 or VEGFR-2 gene results in embryonic lethality between days 8.5 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140599 16104843 185062 10981 6307 KDR VEGFR2 VEGFR-2 6 4.3 Homozygous loss of the VEGFR-1 or VEGFR-2 gene results in embryonic lethality between days 8.5 and 9.5 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140600 16104843 185062 10981 6307 KDR VEGFR VEGFRs 20 3.0 embryonic lethality between days 8.5 and 9.5 indicating that these VEGFRs play important roles in vasculogenesis and angiogenesis 101 102 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140601 16104843 185063 10981 6307 KDR VEGFR2 VEGFR-2 0 4.3 VEGFR-2 mice die due to a lack of endothelial cell growth 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140602 16104843 185064 7629 3763 FLT1 VEGFR1 VEGFR-1 4 0.6 On the other hand VEGFR-1 mice die due to an overgrowth of endothelial cells and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140603 16104843 185065 7629 3763 FLT1 VEGFR1 VEGFR-1 12 0.6 vascular development in mice lacking the tyrosine kinase domain of VEGFR-1 103 has indicated that VEGFR-2 is the major positive signal 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140604 16104843 185065 10981 6307 KDR VEGFR2 VEGFR-2 19 4.3 the tyrosine kinase domain of VEGFR-1 103 has indicated that VEGFR-2 is the major positive signal transducer whereas VEGFR-1 has a 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140605 16104843 185065 7629 3763 FLT1 VEGFR1 VEGFR-1 27 0.6 indicated that VEGFR-2 is the major positive signal transducer whereas VEGFR-1 has a negative regulatory role in angiogenesis early in embryogenesis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140606 16104843 185066 23910 12680 VEGFA VEGF-A VEGF-A-dependent 15 5.8 76 have shown that Tyr and Tyr are two major VEGF-A-dependent autophosphorylation sites in VEGFR-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140607 16104843 185066 10981 6307 KDR VEGFR2 VEGFR-2 19 4.3 Tyr and Tyr are two major VEGF-A-dependent autophosphorylation sites in VEGFR-2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140608 16104843 185067 23910 12680 VEGFA VEGF VEGF-dependent 8 5.8 However only autophosphorylation of Tyr is crucial for VEGF-dependent endothelial cell proliferation via the PLC-g /PKC/Raf/MEK PKC Raf MEK 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140609 16104843 185067 12337 6871 MAPK1 MAPK MAPK 17 2.2 cell proliferation via the PLC-g /PKC/Raf/MEK PKC Raf MEK [MAPK/ERK MAPK ERK (extracellular-signal-regulated extracellular-signal-regulated kinase kinase]/ERK kinase ERK pathway 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140610 16104843 185067 12337 6871 MAPK1 ERK ERK 17 2.2 proliferation via the PLC-g /PKC/Raf/MEK PKC Raf MEK [MAPK/ERK MAPK ERK (extracellular-signal-regulated extracellular-signal-regulated kinase kinase]/ERK kinase ERK pathway 1 JUMiner_v2.2 1 0 0 2 6871 TotalCon:2<>3393|EPHB2|2048|Complete__6871|MAPK1|5594|Complete__<>AvaiableGeneRif=2<>BEST:6871|MAPK1|0.000793653030225563<>ScoreDetail__3393|EPHB2|0.000520126560233578__6871|MAPK1|0.000793653030225563__ 0 0 0 0 0 140611 16104843 185067 12337 6871 MAPK1 ERK ERK 20 2.2 Raf MEK [MAPK/ERK MAPK ERK (extracellular-signal-regulated extracellular-signal-regulated kinase kinase]/ERK kinase ERK pathway 1 JUMiner_v2.2 1 0 0 2 6871 TotalCon:2<>3393|EPHB2|2048|Complete__6871|MAPK1|5594|Complete__<>AvaiableGeneRif=2<>BEST:6871|MAPK1|0.000793653030225563<>ScoreDetail__3393|EPHB2|0.000520126560233578__6871|MAPK1|0.000793653030225563__ 0 0 0 0 0 140612 16104843 185068 10981 6307 KDR VEGFR2 VEGFR-2 7 4.3 An unusual feature of mitogenic signalling from VEGFR-2 is the requirement for PKC but not Ras 104 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140613 16104843 185069 10981 6307 KDR VEGFR2 VEGFR-2 16 4.3 knockin mice substituting Tyr (corresponding corresponding to Tyr in human VEGFR-2 and Tyr (Tyr Tyr in human of the VEGFR-2 gene 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140614 16104843 185069 10981 6307 KDR VEGFR2 VEGFR-2 24 4.3 human VEGFR-2 and Tyr (Tyr Tyr in human of the VEGFR-2 gene with phenylalanine has revealed that the signalling via Tyr 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140615 16104843 185069 10981 6307 KDR VEGFR2 VEGFR-2 36 4.3 with phenylalanine has revealed that the signalling via Tyr of VEGFR-2 is essential for endothelial and haematopoietic development during embryogenesis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140616 16104843 185070 3983 1736 CDC42 CDC42 Cdc42 16 0.3 appears to be required to trigger the sequential activation of Cdc42 and p38 MAPK and to drive p38 MAPK-mediated actin remodelling 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140617 16104843 185070 12337 6871 MAPK1 p38 p38 18 2.2 be required to trigger the sequential activation of Cdc42 and p38 MAPK and to drive p38 MAPK-mediated actin remodelling in stress 1 JUMiner_v2.2 1 0 0 2 6878 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6878|MAPK4|0.000820263796837063<>ScoreDetail__1189|AHSA1|0.00033685499923442__6878|MAPK4|0.000820263796837063__6871|MAPK1|0.000783615282658543__6876|MAPK14|0.000706125935182395__ 0 0 0 0 0 140618 16104843 185070 12337 6871 MAPK1 MAPK MAPK 19 2.2 required to trigger the sequential activation of Cdc42 and p38 MAPK and to drive p38 MAPK-mediated actin remodelling in stress fibres 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140619 16104843 185070 12337 6871 MAPK1 p38 p38 23 2.2 sequential activation of Cdc42 and p38 MAPK and to drive p38 MAPK-mediated actin remodelling in stress fibres in endothelial cells exposed 1 JUMiner_v2.2 1 0 0 2 6878 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6878|MAPK4|0.000820263796837063<>ScoreDetail__1189|AHSA1|0.00033685499923442__6878|MAPK4|0.000820263796837063__6871|MAPK1|0.000783615282658543__6876|MAPK14|0.000706125935182395__ 0 0 0 0 0 140620 16104843 185070 12337 6871 MAPK1 MAPK MAPK-mediated 24 2.2 activation of Cdc42 and p38 MAPK and to drive p38 MAPK-mediated actin remodelling in stress fibres in endothelial cells exposed to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140621 16104843 185070 23910 12680 VEGFA VEGF-A VEGF-A 35 7.6 actin remodelling in stress fibres in endothelial cells exposed to VEGF-A 106 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140622 16104843 185071 16613 8975 PIK3CA PI3K PI3K 4 1.0 The activation of the PI3K/p70 PI3K p70 S6K (S6 S6 kinase pathway by VEGFR-2 is also 1 JUMiner_v2.2 1 0 0 2 8978 TotalCon:3<>8975|PIK3CA|5290|Complete__8976|PIK3CB|5291|Complete__8978|PIK3CG|5294|Complete__<>AvaiableGeneRif=3<>BEST:8978|PIK3CG|0.00206242925388024<>ScoreDetail__8976|PIK3CB|0.00117343649258543__8978|PIK3CG|0.00206242925388024__8975|PIK3CA|0.0010350674023782__ 0 0 0 0 0 140623 16104843 185071 23515 29884 UBASH3B p70 p70 4 0.6 The activation of the PI3K/p70 PI3K p70 S6K (S6 S6 kinase pathway by VEGFR-2 is also involved 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140624 16104843 185071 19050 10436 RPS6KB1 S6K S6K 5 1.0 The activation of the PI3K/p70 PI3K p70 S6K (S6 S6 kinase pathway by VEGFR-2 is also involved in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140625 16104843 185071 10981 6307 KDR VEGFR2 VEGFR-2 10 4.3 the PI3K/p70 PI3K p70 S6K (S6 S6 kinase pathway by VEGFR-2 is also involved in VEGF-A-induced endothelial cell proliferation 107 ( 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140626 16104843 185071 23910 12680 VEGFA VEGF-A VEGF-A-induced 15 5.8 (S6 S6 kinase pathway by VEGFR-2 is also involved in VEGF-A-induced endothelial cell proliferation 107 ( Figure 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140627 16104843 185072 6725 18173 ERAP1 PILSAP PILSAP 0 1.3 PILSAP (puromycin-intensive puromycin-intensive leucyl-specific aminopeptidase plays a crucial role in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140628 16104843 185072 16345 8816 PDPK1 PDK1 PDK1 20 1.6 activation of this pathway via the binding and modification of PDK1 (phosphoinositide-dependent phosphoinositide-dependent kinase 1 108 1 JUMiner_v2.2 1 0 0 2 8816 TotalCon:2<>8809|PDK1|5163|Complete__8816|PDPK1|5170|Complete__<>AvaiableGeneRif=2<>BEST:8816|PDPK1|0.000618939836549924<>ScoreDetail__8816|PDPK1|0.000618939836549924__8809|PDK1|0.000529175310985141__ 0 0 0 0 0 140629 16104843 185073 23910 12680 VEGFA VEGF VEGF-induced 10 5.8 In addition recent studies have revealed various downstream mediators of VEGF-induced angiogenic signalling such as diacylglycerol kinase a 109 SRF (serum 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140630 16104843 185073 21251 11291 SRF SRF SRF 21 1.2 of VEGF-induced angiogenic signalling such as diacylglycerol kinase a 109 SRF (serum serum response factor 110 SREBP (sterol-regulatory-element-binding sterol-regulatory-element-binding protein 111 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140631 16104843 185073 10655 6110 IQGAP1 IQGAP1 IQGAP1 35 0.6 serum response factor 110 SREBP (sterol-regulatory-element-binding sterol-regulatory-element-binding protein 111 and IQGAP1 112 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140632 16104843 185074 23910 12680 VEGFA VEGF VEGF-induced 11 5.8 using DNA microarrays have reported possible endogenous feedback inhibitors for VEGF-induced angiogenesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140633 16104843 185075 18124 3040 RCAN1 DSCR1 DSCR1 2 1.6 Vasohibin and DSCR1 (Down Down syndrome critical region protein 1 are significantly induced 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140634 16104843 185075 23910 12680 VEGFA VEGF VEGF 13 10.4 Down syndrome critical region protein 1 are significantly induced by VEGF in endothelial cells 113 114 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140635 16104843 185076 18124 3040 RCAN1 DSCR1 DSCR1 2 1.6 Up-regulation of DSCR1 in endothelial cells inhibits the nuclear localization of NFAT (nuclear 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140636 16104843 185078 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A is known to increase the vascular permeability of microvessels to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140637 16104843 185080 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A significantly accumulates in malignant ascites 116 and pleural effusion 117 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140638 16104843 185081 23910 12680 VEGFA VEGF-A VEGF-A 10 7.6 Consistent with a role in the regulation of vascular permeability VEGF-A induces endothelial fenestration in some vascular beds and in cultured 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140639 16104843 185082 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A increases vascular permeability in mesenteric microvessels by activation of VEGFR-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140640 16104843 185082 10981 6307 KDR VEGFR2 VEGFR-2 10 4.3 VEGF-A increases vascular permeability in mesenteric microvessels by activation of VEGFR-2 on endothelial cells and subsequent activation of PLC 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140641 16104843 185082 16745 9065 PLCG1 PLC PLC 18 0.9 activation of VEGFR-2 on endothelial cells and subsequent activation of PLC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140642 16104843 185084 10981 6307 KDR VEGFR2 VEGFR-2 9 4.3 Other studies have also demonstrated the crucial role of VEGFR-2 signalling in the enhancement of vascular permeability however our recent 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140643 16104843 185084 7629 3763 FLT1 VEGFR1 VEGFR-1 41 0.6 enhancement of vascular permeability is intensified by the activation of VEGFR-1 more than the proliferation of endothelial cells under some active 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140644 16104843 185084 10981 6307 KDR VEGFR2 VEGFR-2 54 4.3 the proliferation of endothelial cells under some active signalling from VEGFR-2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140645 16104843 185085 7629 3763 FLT1 VEGFR1 VEGFR-1 6 0.6 This finding indicates the importance of VEGFR-1 signalling in vascular permeability 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140646 16104843 185086 23910 12680 VEGFA VEGF VEGF-dependent 15 5.8 in specific Src family kinases has demonstrated no decrease in VEGF-dependent neovascularization but a complete ablation of vascular permeability in Src 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140647 16104843 185086 21242 11283 SRC SRC Src 7 0.0 An analysis of mice deficient in specific Src family kinases has demonstrated no decrease in VEGF-dependent neovascularization but 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140648 16104843 185086 21242 11283 SRC SRC Src 25 0.0 VEGF-dependent neovascularization but a complete ablation of vascular permeability in Src or Yes mice whereas Fyn mice show no such defect 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140649 16104843 185086 24357 12841 YES1 Yes Yes 27 0.0 but a complete ablation of vascular permeability in Src or Yes mice whereas Fyn mice show no such defect 119 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140650 16104843 185087 10981 6307 KDR VEGFR2 VEGFR-2 12 4.3 blockade of Src prevents the disassociation of a complex comprising VEGFR-2 VE-cadherin and b -catenin with the same kinetics with which 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140651 16104843 185087 23910 12680 VEGFA VEGF VEGF-mediated 25 5.8 b -catenin with the same kinetics with which it prevents VEGF-mediated vascular permeability and oedema 120 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140652 16104843 185087 21242 11283 SRC SRC Src 4 0.0 In addition blockade of Src prevents the disassociation of a complex comprising VEGFR-2 VE-cadherin and 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140653 16104843 185088 23910 12680 VEGFA VEGF VEGF-induced 15 5.8 activity of specific Src family kinases is essential for the VEGF-induced enhancement of vascular permeability through the disruption of the VEGFR-2/cadherin/catenin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140654 16104843 185088 10981 6307 KDR VEGFR2 VEGFR-2 25 4.3 enhancement of vascular permeability through the disruption of the VEGFR-2/cadherin/catenin VEGFR-2 cadherin catenin complex 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140655 16104843 185088 4024 1756 CDH17 cadherin cadherin 25 0.3 of vascular permeability through the disruption of the VEGFR-2/cadherin/catenin VEGFR-2 cadherin catenin complex 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140656 16104843 185088 21242 11283 SRC SRC Src 8 0.0 These findings indicate that the activity of specific Src family kinases is essential for the VEGF-induced enhancement of vascular 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140657 16104843 185089 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A can induce production of NO and endogenous NO can increase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140658 16104843 185090 14533 7872 NOS1 NOS NOS 5 0.9 Among the three isoforms of NOS (NO NO synthase eNOS (endothelial endothelial NOS plays a predominant 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000522440000217723<>ScoreDetail__7873|NOS2A|0.000522440000217723__7872|NOS1|0.000468158231875689__ 0 0 0 0 0 140659 16104843 185090 14538 7876 NOS3 eNOS eNOS 8 1.9 Among the three isoforms of NOS (NO NO synthase eNOS (endothelial endothelial NOS plays a predominant role in VEGF-induced angiogenesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140660 16104843 185090 14533 7872 NOS1 NOS NOS 10 0.9 three isoforms of NOS (NO NO synthase eNOS (endothelial endothelial NOS plays a predominant role in VEGF-induced angiogenesis and vascular permeability 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000522440000217723<>ScoreDetail__7873|NOS2A|0.000522440000217723__7872|NOS1|0.000468158231875689__ 0 0 0 0 0 140661 16104843 185090 23910 12680 VEGFA VEGF VEGF-induced 16 5.8 synthase eNOS (endothelial endothelial NOS plays a predominant role in VEGF-induced angiogenesis and vascular permeability 122 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140662 16104843 185091 14538 7876 NOS3 eNOS eNOS 4 1.9 Furthermore the activation of eNOS is regulated by the PI3K/Akt PI3K Akt pathway 123 124 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140663 16104843 185091 16613 8975 PIK3CA PI3K PI3K 9 1.0 Furthermore the activation of eNOS is regulated by the PI3K/Akt PI3K Akt pathway 123 124 1 JUMiner_v2.2 1 0 0 2 8978 TotalCon:3<>8975|PIK3CA|5290|Complete__8976|PIK3CB|5291|Complete__8978|PIK3CG|5294|Complete__<>AvaiableGeneRif=3<>BEST:8978|PIK3CG|0.00206242925388024<>ScoreDetail__8976|PIK3CB|0.00117343649258543__8978|PIK3CG|0.00206242925388024__8975|PIK3CA|0.0010350674023782__ 0 0 0 0 0 140664 16104843 185091 543 391 AKT1 AKT Akt 9 0.3 the activation of eNOS is regulated by the PI3K/Akt PI3K Akt pathway 123 124 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140665 16104843 185092 13812 32159 MTG1 GTP GTP-binding 2 0.5 The small GTP-binding protein Rac which is also activated by PI3K has been 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 140666 16104843 185092 543 391 AKT1 RAC Rac 4 1.1 The small GTP-binding protein Rac which is also activated by PI3K has been implicated in 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140667 16104843 185092 16613 8975 PIK3CA PI3K PI3K 10 1.0 The small GTP-binding protein Rac which is also activated by PI3K has been implicated in the regulation of vascular permeability 125 1 JUMiner_v2.2 1 0 0 2 8978 TotalCon:3<>8975|PIK3CA|5290|Complete__8976|PIK3CB|5291|Complete__8978|PIK3CG|5294|Complete__<>AvaiableGeneRif=3<>BEST:8978|PIK3CG|0.00206242925388024<>ScoreDetail__8976|PIK3CB|0.00117343649258543__8978|PIK3CG|0.00206242925388024__8975|PIK3CA|0.0010350674023782__ 0 0 0 0 0 140668 16104843 185093 12337 6871 MAPK1 p38 p38 11 2.2 A recent study 126 has shown that inhibition of p38 MAPK activity abrogated VEGF-induced vascular permeability in vivo and in 1 JUMiner_v2.2 1 0 0 2 6878 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6878|MAPK4|0.000820263796837063<>ScoreDetail__1189|AHSA1|0.00033685499923442__6878|MAPK4|0.000820263796837063__6871|MAPK1|0.000783615282658543__6876|MAPK14|0.000706125935182395__ 0 0 0 0 0 140669 16104843 185093 12337 6871 MAPK1 MAPK MAPK 12 2.2 A recent study 126 has shown that inhibition of p38 MAPK activity abrogated VEGF-induced vascular permeability in vivo and in vitro 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140670 16104843 185093 23910 12680 VEGFA VEGF VEGF-induced 15 5.8 126 has shown that inhibition of p38 MAPK activity abrogated VEGF-induced vascular permeability in vivo and in vitro suggesting the involvement 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140671 16104843 185093 12337 6871 MAPK1 p38 p38 28 2.2 permeability in vivo and in vitro suggesting the involvement of p38 MAPK in the control of vascular permeability ( Figure 2 1 JUMiner_v2.2 1 0 0 2 6878 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6878|MAPK4|0.000820263796837063<>ScoreDetail__1189|AHSA1|0.00033685499923442__6878|MAPK4|0.000820263796837063__6871|MAPK1|0.000783615282658543__6876|MAPK14|0.000706125935182395__ 0 0 0 0 0 140672 16104843 185093 12337 6871 MAPK1 MAPK MAPK 29 2.2 in vivo and in vitro suggesting the involvement of p38 MAPK in the control of vascular permeability ( Figure 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140673 16104843 185095 23910 12680 VEGFA VEGF-A VEGF-A 4 7.6 Numerous studies have established VEGF-A as a key angiogenic player in cancer 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140674 16104843 185096 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A is expressed in most tumours and its expression correlates with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140675 16104843 185097 23910 12680 VEGFA VEGF-A VEGF-A 13 7.6 tumour cells tumour-associated stroma is also an important source of VEGF-A 127 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140676 16104843 185099 23910 12680 VEGFA VEGF-A VEGF-A 3 7.6 The expression of VEGF-A mRNA is highest in hypoxic tumour cells adjacent to necrotic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140677 16104843 185099 23910 12680 VEGFA VEGF-A VEGF-A 23 7.6 adjacent to necrotic areas 16 indicating that the induction of VEGF-A by hypoxia in growing tumours can change the balance of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140678 16104843 185100 23910 12680 VEGFA VEGF VEGF 6 10.4 Consistent with this hypothesis capturing of VEGF or blocking of its signalling receptor VEGFR-2 by a VEGFR 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140679 16104843 185100 10981 6307 KDR VEGFR2 VEGFR-2 13 4.3 hypothesis capturing of VEGF or blocking of its signalling receptor VEGFR-2 by a VEGFR tyrosine kinase inhibitor antisense oligonucleotides vaccination or 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140680 16104843 185100 10981 6307 KDR VEGFR VEGFR 16 3.3 VEGF or blocking of its signalling receptor VEGFR-2 by a VEGFR tyrosine kinase inhibitor antisense oligonucleotides vaccination or neutralizing antibodies reduced 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140681 16104843 185101 7629 3763 FLT1 VEGFR1 VEGFR-1 4 0.6 Unlike in physiological angiogenesis VEGFR-1 signalling plays an important role in angiogenesis under pathological conditions 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140682 16104843 185102 16459 8893 PGF PlGF PlGF 9 4.6 Autiero et al 131 have proposed that PlGF regulates inter- and intra-molecular cross-talk between VEGFR-1 and VEGFR-2 amplifying 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140683 16104843 185102 7629 3763 FLT1 VEGFR1 VEGFR-1 16 0.6 have proposed that PlGF regulates inter- and intra-molecular cross-talk between VEGFR-1 and VEGFR-2 amplifying VEGF-driven angiogenesis through VEGFR-2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140684 16104843 185102 10981 6307 KDR VEGFR2 VEGFR-2 18 4.3 that PlGF regulates inter- and intra-molecular cross-talk between VEGFR-1 and VEGFR-2 amplifying VEGF-driven angiogenesis through VEGFR-2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140685 16104843 185102 23910 12680 VEGFA VEGF VEGF-driven 20 5.8 regulates inter- and intra-molecular cross-talk between VEGFR-1 and VEGFR-2 amplifying VEGF-driven angiogenesis through VEGFR-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140686 16104843 185102 10981 6307 KDR VEGFR2 VEGFR-2 23 4.3 intra-molecular cross-talk between VEGFR-1 and VEGFR-2 amplifying VEGF-driven angiogenesis through VEGFR-2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140687 16104843 185103 23910 12680 VEGFA VEGF VEGF 7 10.4 Several studies also describe the role of VEGF in carcinogenesis 132 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140688 16104843 185106 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A and VEGFRs are constitutively expressed in the islet vasculature before 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140689 16104843 185106 10981 6307 KDR VEGFR VEGFRs 2 3.0 VEGF-A and VEGFRs are constitutively expressed in the islet vasculature before and after 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140690 16104843 185106 23910 12680 VEGFA VEGF-A VEGF-A 24 7.6 the initiation of angiogenesis (angiogenic angiogenic switch 133 however when VEGF-A is absent from islet b -cells of Rip1-Tag2 mice both 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140691 16104843 185106 23910 12680 VEGFA VEGF-A VEGF-A 52 7.6 well as tumour growth are severely disrupted 134 indicating that VEGF-A plays a critical role in angiogenic switching and carcinogenesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140692 16104843 185107 23910 12680 VEGFA VEGF-A VEGF-A 24 7.6 a component of the angiogenic switch as this proteinase makes VEGF-A available for the interaction with its receptors by releasing sequestered 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140693 16104843 185107 23910 12680 VEGFA VEGF-A VEGF-A 35 7.6 available for the interaction with its receptors by releasing sequestered VEGF-A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140694 16104843 185108 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A impairs the endothelial barrier by disrupting a VE-cadherin/ VE-cadherin b 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140695 16104843 185108 21242 11283 SRC SRC Src 16 0.0 a VE-cadherin/ VE-cadherin b -catenin complex via the activation of Src and facilitates tumour cell extravasation and metastasis 136 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140696 16104843 185109 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A also induces the disruption of hepatocellular tight junctions which may 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140697 16104843 185110 10981 6307 KDR VEGFR2 VEGFR-2 3 4.3 Pharmacological blockade of VEGFR-2 stabilizes the endothelial barrier function and suppresses tumour cell extravasation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140698 16104843 185110 10981 6307 KDR VEGFR2 VEGFR-2 23 4.3 tumour cell extravasation in vivo 136 suggesting the importance of VEGFR-2 signalling in this kind of tumour invasion and metastasis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140699 16104843 185111 7629 3763 FLT1 VEGFR1 VEGFR-1 9 0.6 Hiratsuka et al 138 have shown that VEGFR-1 signalling is also involved in tumour metastasis being linked to 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140700 16104843 185111 13327 7176 MMP9 MMP-9 MMP-9 23 1.3 involved in tumour metastasis being linked to the induction of MMP-9 in lung endothelial cells and to the facilitation of lung-specific 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140701 16104843 185114 23910 12680 VEGFA VEGF VEGF 4 10.4 Besides bevacizumab many other VEGF inhibitors are being pursued clinically 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140702 16104843 185117 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF acts as a pro-inflammatory cytokine by increasing the permeability of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140703 16104843 185118 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF is strongly expressed by epidermal keratinocytes in wound healing and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140704 16104843 185119 23910 12680 VEGFA VEGF-A VEGF-A 4 7.6 Transgenic mice that overexpress VEGF-A specifically in the epidermis exhibit an increased density of tortuous 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140705 16104843 185119 23910 12680 VEGFA VEGF-A VEGF-A 36 7.6 adhesion in postcapillary skin venules suggesting that enhanced expression of VEGF-A in epidermal keratinocytes is sufficient to develop psoriasis-like inflammatory skin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140706 16104843 185120 23910 12680 VEGFA VEGF-A VEGF-A 2 7.6 Moreover heterozygous VEGF-A transgenic mice which do not spontaneously develop inflammatory skin lesions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140707 16104843 185121 16459 8893 PGF PlGF-2 PlGF-2 3 3.1 Transgenic overexpression of PlGF-2 in epidermal keratinocytes also results in a significantly increased inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140708 16104843 185121 16459 8893 PGF PlGF PlGF 19 4.6 in a significantly increased inflammatory response whereas a deficiency of PlGF results in a diminished and abbreviated inflammatory response 145 suggesting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140709 16104843 185121 7629 3763 FLT1 VEGFR1 VEGFR-1 35 0.6 diminished and abbreviated inflammatory response 145 suggesting the importance of VEGFR-1 signalling in chronic skin inflammation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140710 16104843 185122 23910 12680 VEGFA VEGF-A VEGF-A 3 7.6 Local production of VEGF-A in arthritic synovial tissue has been documented 16 and appears 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140711 16104843 185123 23910 12680 VEGFA VEGF-A VEGF-A 1 7.6 Subsequently VEGF-A has been shown to be important in the pathogenesis of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140712 16104843 185124 7629 3763 FLT1 VEGFR1 VEGFR-1 25 0.6 by suppressing synovial inflammation and neovascularization emphasizing the importance of VEGFR-1 signalling in the destruction 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140713 16104843 185126 23911 12681 VEGFB VEGFB VEGF-B 6 1.8 The reduction of synovial inflammation in VEGF-B mice 47 also implies a critical role for VEGFR-1 signalling 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140714 16104843 185126 7629 3763 FLT1 VEGFR1 VEGFR-1 17 0.6 in VEGF-B mice 47 also implies a critical role for VEGFR-1 signalling in RA 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140715 16104843 185127 23910 12680 VEGFA VEGF-A VEGF-A 3 7.6 Exaggerated levels of VEGF-A have been detected in tissues and biological samples from people 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140716 16104843 185128 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF has been postulated to contribute to asthmatic tissue oedema through 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140717 16104843 185129 23910 12680 VEGFA VEGF VEGF 5 10.4 A recent study using lung-targeted VEGF 165 transgenic mice has revealed a novel function of VEGF-A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140718 16104843 185129 23910 12680 VEGFA VEGF-A VEGF-A 15 7.6 VEGF 165 transgenic mice has revealed a novel function of VEGF-A in allergic responses 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140719 16104843 185130 23910 12680 VEGFA VEGF-A VEGF-A 3 7.6 In these mice VEGF-A induces asthma-like inflammation airway and vascular remodelling and airway hyper-responsiveness 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140720 16104843 185131 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A also enhances respiratory sensitization to antigen as well as T 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140721 16104843 185132 23910 12680 VEGFA VEGF-A VEGF-A 1 7.6 Thus VEGF-A has a critical role in pulmonary T H 2 inflammation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140722 16104843 185133 23910 12680 VEGFA VEGF-A VEGF-A 9 7.6 Other studies have provided evidence for a role for VEGF-A as a pro-inflammatory mediator in allograft rejection 152 and neointimal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140723 16104843 185135 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A mRNA expression not normally found in the adult mouse brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140724 16104843 185135 23910 12680 VEGFA VEGF-A VEGF-A 18 7.6 adult mouse brain is up-regulated after cerebral ischaemia and elevated VEGF-A levels can be detected as early as 3 h after 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140725 16104843 185136 23910 12680 VEGFA VEGF-A VEGF-A 8 7.6 Previous studies have demonstrated that the antagonism of VEGF-A results in reduced oedema and tissue damage after ischaemia implicating 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140726 16104843 185136 23910 12680 VEGFA VEGF-A VEGF-A 19 7.6 results in reduced oedema and tissue damage after ischaemia implicating VEGF-A in the pathophysiology of stroke 155 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140727 16104843 185137 23910 12680 VEGFA VEGF-A VEGF-A-induced 14 5.8 al 156 have reported that Src mice are resistant to VEGF-A-induced vascular permeability and show decreased infarct volumes after stroke 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140728 16104843 185137 21242 11283 SRC SRC Src 9 0.0 Paul et al 156 have reported that Src mice are resistant to VEGF-A-induced vascular permeability and show decreased 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140729 16104843 185138 23910 12680 VEGFA VEGF-A VEGF-A 18 7.6 permeability protecting wild-type mice from ischaemia-induced brain damage without influencing VEGF-A expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140730 16104843 185138 21242 11283 SRC SRC Src 4 0.0 Systemic application of a Src inhibitor suppresses vascular permeability protecting wild-type mice from ischaemia-induced brain 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140731 16104843 185139 23910 12680 VEGFA VEGF-A VEGF-A 13 7.6 Sun et al 157 have reported that intracerebroventricular administration of VEGF-A reduces infarct size improves neurological performance and enhances the delayed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140732 16104843 185140 23910 12680 VEGFA VEGF-A VEGF-A 9 7.6 These conflicting results appear to reflect dual roles of VEGF-A in stroke neuroprotective and pro-inflammatory effects 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140733 16104843 185141 23910 12680 VEGFA VEGF-A VEGF-A 15 7.6 through the internal carotid artery low and intermediate doses of VEGF-A significantly promote neuroprotection of the ischaemic brain whereas a high 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140734 16104843 185141 23910 12680 VEGFA VEGF-A VEGF-A 28 7.6 neuroprotection of the ischaemic brain whereas a high dose of VEGF-A offers no neuroprotection to the ischaemic brain or the damaged 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140735 16104843 185142 23910 12680 VEGFA VEGF-A VEGF-A 9 7.6 Further studies are required for the therapeutic application of VEGF-A against stroke 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140736 16104843 185143 23910 12680 VEGFA VEGF VEGF 8 10.4 Extensive evidence has suggested a causal role of VEGF in several diseases of the human eye in which neovascularization 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140737 16104843 185144 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF levels are increased in the vitreous and retina of patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140738 16104843 185145 23910 12680 VEGFA VEGF VEGF 4 10.4 Subsequent studies using various VEGF inhibitors have confirmed that VEGF plays a central role in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140739 16104843 185145 23910 12680 VEGFA VEGF VEGF 9 10.4 Subsequent studies using various VEGF inhibitors have confirmed that VEGF plays a central role in ischaemia-induced intraocular neovascularization 159 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140740 16104843 185146 651 460 AMDP1 AMD AMD 19 0.0 significant and clinically meaningful benefit in the treatment of neovascular AMD (age-related age-related macular degeneration 160 which is the leading cause 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>460|AMDP1|263|No_GeneRif__457|AMD1|262|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 140741 16104843 185147 23910 12680 VEGFA VEGF VEGF 15 10.4 161 have reported that deletion of the HRE in the VEGF promoter reduces hypoxic VEGF expression in the spinal cord and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140742 16104843 185147 23910 12680 VEGFA VEGF VEGF 19 10.4 deletion of the HRE in the VEGF promoter reduces hypoxic VEGF expression in the spinal cord and causes adult-onset progressive motor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140743 16104843 185147 20996 11179 SOD1 ALS ALS 34 1.0 cord and causes adult-onset progressive motor neuron degeneration reminiscent of ALS (amyotrophic amyotrophic lateral sclerosis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00117767640411015<>ScoreDetail__5468|IGFALS|0.000820142704830641__11179|SOD1|0.00117767640411015__ 0 0 0 0 0 140744 16104843 185148 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF 165 promotes survival of motor neurons during hypoxia through binding 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140745 16104843 185148 10981 6307 KDR VEGFR2 VEGFR-2 11 4.3 165 promotes survival of motor neurons during hypoxia through binding VEGFR-2 and NRP-1 161 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140746 16104843 185148 14682 8004 NRP1 NRP1 NRP-1 13 0.8 survival of motor neurons during hypoxia through binding VEGFR-2 and NRP-1 161 11 JUMiner_v2.2 1 0 0 2 8004 TotalCon:2<>8004|NRP1|8829|Complete__7750|NELL1|4745|Complete__<>AvaiableGeneRif=2<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__8004|NRP1|0.00122944631586111__7750|NELL1|0.000520594089725923__ 0 0 0 0 0 140747 16104843 185149 23910 12680 VEGFA VEGF-A VEGF-A 6 7.6 A subsequent study has revealed that VEGF-A is a modifier associated with motor neuron degeneration in human 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140748 16104843 185149 20996 11179 SOD1 ALS ALS 17 1.0 is a modifier associated with motor neuron degeneration in human ALS and in a mouse model of ALS 162 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00117767640411015<>ScoreDetail__5468|IGFALS|0.000820142704830641__11179|SOD1|0.00117767640411015__ 0 0 0 0 0 140749 16104843 185149 20996 11179 SOD1 ALS ALS 24 1.0 degeneration in human ALS and in a mouse model of ALS 162 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00117767640411015<>ScoreDetail__5468|IGFALS|0.000820142704830641__11179|SOD1|0.00117767640411015__ 0 0 0 0 0 140750 16104843 185150 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A treatment increases the life expectancy of ALS mice without causing 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140751 16104843 185150 20996 11179 SOD1 ALS ALS 7 1.0 VEGF-A treatment increases the life expectancy of ALS mice without causing toxic side effects 163 164 indicating that 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00117767640411015<>ScoreDetail__5468|IGFALS|0.000820142704830641__11179|SOD1|0.00117767640411015__ 0 0 0 0 0 140752 16104843 185150 23910 12680 VEGFA VEGF-A VEGF-A 21 7.6 mice without causing toxic side effects 163 164 indicating that VEGF-A has neuroprotective effects on motor neurons and treatment with VEGF-A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140753 16104843 185150 23910 12680 VEGFA VEGF-A VEGF-A 31 7.6 VEGF-A has neuroprotective effects on motor neurons and treatment with VEGF-A could be one of the most effective therapies for ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140754 16104843 185150 20996 11179 SOD1 ALS ALS 41 1.0 VEGF-A could be one of the most effective therapies for ALS reported so far 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00117767640411015<>ScoreDetail__5468|IGFALS|0.000820142704830641__11179|SOD1|0.00117767640411015__ 0 0 0 0 0 140755 16104843 185151 7629 3763 FLT1 VEGFR1 VEGFR-1 14 0.6 al 165 recently provided evidence for a novel function of VEGFR-1 in LSECs (liver liver sinusoidal endothelial cells 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140756 16104843 185152 7629 3763 FLT1 VEGFR1 VEGFR-1 3 0.6 The activation of VEGFR-1 results in the paracrine release of HGF (hepatocyte hepatocyte growth 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140757 16104843 185152 10463 6018 IL6 HGF HGF 10 1.8 The activation of VEGFR-1 results in the paracrine release of HGF (hepatocyte hepatocyte growth factor IL-6 (interleukin-6) interleukin-6 and other hepatotrophic 1 JUMiner_v2.2 1 0 0 2 4893 TotalCon:3<>4893|HGF|3082|Complete__6018|IL6|3569|Complete__11187|SOS1|6654|Complete__<>AvaiableGeneRif=3<>BEST:4893|HGF|0.00073795741300885<>ScoreDetail__4893|HGF|0.00073795741300885__11187|SOS1|0.000462170139293141__6018|IL6|0.000455393251016017__ 0 0 0 0 0 140758 16104843 185152 10463 6018 IL6 IL-6 IL-6 14 1.8 in the paracrine release of HGF (hepatocyte hepatocyte growth factor IL-6 (interleukin-6) interleukin-6 and other hepatotrophic molecules by LSECs to the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140759 16104843 185153 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A has no direct mitogenic effect on hepatocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140760 16104843 185154 7629 3763 FLT1 VEGFR1 VEGFR-1 1 0.6 A VEGFR-1 agonist protected the liver from CCl 4 -induced damage in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140761 16104843 185154 4986 2412 CRYGEP1 CCL CCl 7 0.0 A VEGFR-1 agonist protected the liver from CCl 4 -induced damage in spite of its inability to induce 14 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>2412|CRYGEP1|200575|No_GeneRif__2410|CRYGC|1420|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 140762 16104843 185156 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF was originally described as a specific angiogenic and permeability-inducing factor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140763 16104843 185157 23910 12680 VEGFA VEGF VEGF 10 10.4 emerging evidence has revealed that the role of the VEGF/VEGFR VEGF VEGFR system extends far beyond previous expectations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140764 16104843 185157 10981 6307 KDR VEGFR VEGFR 10 3.3 evidence has revealed that the role of the VEGF/VEGFR VEGF VEGFR system extends far beyond previous expectations 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140765 16104843 185158 23910 12680 VEGFA VEGF VEGF 5 10.4 First a wide variety of VEGF family proteins and numerous splicing variants have been identified and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140766 16104843 185159 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF family proteins have been utilized even in snake venoms and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140767 16104843 185160 10981 6307 KDR VEGFR VEGFRs 3 3.0 Secondly several different VEGFRs have been shown to be essential but the interaction between 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140768 16104843 185161 7629 3763 FLT1 VEGFR1 VEGFR-1 0 0.6 VEGFR-1 has a negative regulatory role in embryonic angiogenesis but functions 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140769 16104843 185161 10981 6307 KDR VEGFR2 VEGFR-2 24 4.3 signal transducer in some cases individually and sometimes synergistically with VEGFR-2 via the intra- and inter-molecular cross-talk between these two receptors 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140770 16104843 185162 10981 6307 KDR VEGFR2 VEGFR-2 3 4.3 An association between VEGFR-2 and VEGFR-3 has also been reported 166 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140771 16104843 185162 7632 3767 FLT4 VEGFR3 VEGFR-3 5 0.6 An association between VEGFR-2 and VEGFR-3 has also been reported 166 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140772 16104843 185163 23910 12680 VEGFA VEGF VEGF 7 10.4 Thirdly it has been shown that the VEGF/VEGFR VEGF VEGFR system has multiple functions such as the induction of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140773 16104843 185163 10981 6307 KDR VEGFR VEGFR 7 3.3 Thirdly it has been shown that the VEGF/VEGFR VEGF VEGFR system has multiple functions such as the induction of tumour 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140774 16104843 185164 23910 12680 VEGFA VEGF VEGF 0 10.4 VEGF is also important for memory and learning 167 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140775 16104843 185165 23910 12680 VEGFA VEGF VEGF 11 10.4 other molecules have been found to associate with the VEGF/VEGFR VEGF VEGFR system 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140776 16104843 185165 10981 6307 KDR VEGFR VEGFR 11 3.3 molecules have been found to associate with the VEGF/VEGFR VEGF VEGFR system 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140777 16104843 185166 23910 12680 VEGFA VEGF VEGF 11 10.4 are required to achieve a comprehensive understanding of the VEGF/VEGFR VEGF VEGFR system however the recent progress in the molecular and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140778 16104843 185166 10981 6307 KDR VEGFR VEGFR 11 3.3 required to achieve a comprehensive understanding of the VEGF/VEGFR VEGF VEGFR system however the recent progress in the molecular and biological 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140779 16104843 185169 23910 12680 VEGFA VEGF VEGF 11 10.4 angiogenesis inflammation signal transduction tumour vascular endothelial growth factor (VEGF), VEGF vascular permeability 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140780 16104843 185170 20996 11179 SOD1 ALS ALS 1 1.0 Abbreviations ALS amyotrophic lateral sclerosis DSCR1 Down syndrome critical region protein 1 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00117767640411015<>ScoreDetail__5468|IGFALS|0.000820142704830641__11179|SOD1|0.00117767640411015__ 0 0 0 0 0 140781 16104843 185170 18124 3040 RCAN1 DSCR1 DSCR1 5 1.6 Abbreviations ALS amyotrophic lateral sclerosis DSCR1 Down syndrome critical region protein 1 ECM extracellular matrix ERK 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140782 16104843 185170 13346 7178 MMRN1 ECM ECM 12 0.3 amyotrophic lateral sclerosis DSCR1 Down syndrome critical region protein 1 ECM extracellular matrix ERK extracellular signal-regulated kinase FAK focal adhesion kinase 3 JUMiner_v2.2 1 2 extracellular matrix 0 0 0 0 0 0 0 0 140783 16104843 185170 12337 6871 MAPK1 ERK ERK 15 2.2 DSCR1 Down syndrome critical region protein 1 ECM extracellular matrix ERK extracellular signal-regulated kinase FAK focal adhesion kinase HIF-1 hypoxia-inducible factor-1 1 JUMiner_v2.2 1 0 0 2 6871 TotalCon:2<>3393|EPHB2|2048|Complete__6871|MAPK1|5594|Complete__<>AvaiableGeneRif=2<>BEST:6871|MAPK1|0.000793653030225563<>ScoreDetail__3393|EPHB2|0.000520126560233578__6871|MAPK1|0.000793653030225563__ 0 0 0 0 0 140784 16104843 185170 17616 9611 PTK2 FAK FAK 19 0.3 region protein 1 ECM extracellular matrix ERK extracellular signal-regulated kinase FAK focal adhesion kinase HIF-1 hypoxia-inducible factor-1 HRE hypoxia response element 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140785 16104843 185170 9230 4910 HIF1A HIF-1 HIF-1 23 0.6 extracellular matrix ERK extracellular signal-regulated kinase FAK focal adhesion kinase HIF-1 hypoxia-inducible factor-1 HRE hypoxia response element HUVEC human umbilical vein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140786 16104843 185170 12337 6871 MAPK1 MAPK MAPK 44 2.2 endothelial cell LSEC liver sinusoidal endothelial cell mAb monoclonal antibody MAPK mitogen-activated protein kinase MMP matrix metalloproteinase NFATc nuclear factor of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140787 16104843 185170 14338 7775 NFATC1 NFATc NFATc 51 2.5 mAb monoclonal antibody MAPK mitogen-activated protein kinase MMP matrix metalloproteinase NFATc nuclear factor of activated T-cell NO nitric oxide NOS NO 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140788 16104843 185170 14533 7872 NOS1 NOS NOS 60 0.9 metalloproteinase NFATc nuclear factor of activated T-cell NO nitric oxide NOS NO synthase eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000522440000217723<>ScoreDetail__7873|NOS2A|0.000522440000217723__7872|NOS1|0.000468158231875689__ 0 0 0 0 0 140789 16104843 185170 14538 7876 NOS3 eNOS eNOS 63 1.9 factor of activated T-cell NO nitric oxide NOS NO synthase eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140790 16104843 185170 14533 7872 NOS1 NOS NOS 65 0.9 activated T-cell NO nitric oxide NOS NO synthase eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000522440000217723<>ScoreDetail__7873|NOS2A|0.000522440000217723__7872|NOS1|0.000468158231875689__ 0 0 0 0 0 140791 16104843 185170 14682 8004 NRP1 NRP NRP 66 0.8 T-cell NO nitric oxide NOS NO synthase eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase 1 13 JUMiner_v2.2 1 0 0 2 8004 TotalCon:3<>7637|NAP1L1|4673|Complete__8004|NRP1|8829|Complete__17142|OPTN|10133|Complete__<>AvaiableGeneRif=3<>BEST:8004|NRP1|0.00122944631586111<>ScoreDetail__7637|NAP1L1|0.000712684957057947__8004|NRP1|0.00122944631586111__17142|OPTN|0.000391130231927032__ 0 0 0 0 0 140792 16104843 185170 16010 17970 PAIP2 PAIP2 PAIP2 68 0.6 nitric oxide NOS NO synthase eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase 1 PI3K phosphoinositide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140793 16104843 185170 16345 8816 PDPK1 PDK1 PDK1 73 1.6 eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase 1 PI3K phosphoinositide 3-kinase PILSAP puromycin-intensive leucyl-specific aminopeptidase 1 JUMiner_v2.2 1 0 0 2 8816 TotalCon:2<>8809|PDK1|5163|Complete__8816|PDPK1|5170|Complete__<>AvaiableGeneRif=2<>BEST:8816|PDPK1|0.000618939836549924<>ScoreDetail__8816|PDPK1|0.000618939836549924__8809|PDK1|0.000529175310985141__ 0 0 0 0 0 140794 16104843 185170 16613 8975 PIK3CA PI3K PI3K 77 1.0 neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase 1 PI3K phosphoinositide 3-kinase PILSAP puromycin-intensive leucyl-specific aminopeptidase PKC protein kinase C 1 JUMiner_v2.2 1 0 0 2 8978 TotalCon:3<>8975|PIK3CA|5290|Complete__8976|PIK3CB|5291|Complete__8978|PIK3CG|5294|Complete__<>AvaiableGeneRif=3<>BEST:8978|PIK3CG|0.00206242925388024<>ScoreDetail__8976|PIK3CB|0.00117343649258543__8978|PIK3CG|0.00206242925388024__8975|PIK3CA|0.0010350674023782__ 0 0 0 0 0 140795 16104843 185170 6725 18173 ERAP1 PILSAP PILSAP 80 1.3 protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase 1 PI3K phosphoinositide 3-kinase PILSAP puromycin-intensive leucyl-specific aminopeptidase PKC protein kinase C PLC phospholipase C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140796 16104843 185170 16745 9065 PLCG1 PLC PLC 88 0.9 phosphoinositide 3-kinase PILSAP puromycin-intensive leucyl-specific aminopeptidase PKC protein kinase C PLC phospholipase C PlGF placenta growth factor pVHL von Hippel-Lindau tumour 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140797 16104843 185170 16459 8893 PGF PlGF PlGF 91 4.6 puromycin-intensive leucyl-specific aminopeptidase PKC protein kinase C PLC phospholipase C PlGF placenta growth factor pVHL von Hippel-Lindau tumour suppressor protein RA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140798 16104843 185170 19050 10436 RPS6KB1 S6K S6K 108 1.0 tumour suppressor protein RA rheumatoid arthritis RTK receptor tyrosine kinase S6K S6 kinase Tag T antigen T H 2 T-helper type 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140799 16104843 185170 20149 10919 SLC14A2 UTR UTR 120 0.3 kinase Tag T antigen T H 2 T-helper type 2 UTR untranslated region VEGF vascular endothelial growth factor VEGFR VEGF receptor 11 JUMiner_v2.2 1 2 untranslated region 0 2 4468 TotalCon:2<>10919|SLC14A2|8170|Complete__4468|UTS2R|2837|Complete__<>AvaiableGeneRif=2<>BEST:4468|UTS2R|0.000718341656974755<>ScoreDetail__10919|SLC14A2|0.000381768999132343__4468|UTS2R|0.000718341656974755__ 0 0 0 0 0 140800 16104843 185170 23910 12680 VEGFA VEGF VEGF 123 10.4 antigen T H 2 T-helper type 2 UTR untranslated region VEGF vascular endothelial growth factor VEGFR VEGF receptor sVEGFR-1 soluble VEGFR-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140801 16104843 185170 10981 6307 KDR VEGFR VEGFR 128 3.3 type 2 UTR untranslated region VEGF vascular endothelial growth factor VEGFR VEGF receptor sVEGFR-1 soluble VEGFR-1 svVEGF snake venom VEGF Tf 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140802 16104843 185170 23910 12680 VEGFA VEGF VEGF 129 10.4 2 UTR untranslated region VEGF vascular endothelial growth factor VEGFR VEGF receptor sVEGFR-1 soluble VEGFR-1 svVEGF snake venom VEGF Tf svVEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140803 16104843 185170 7629 3763 FLT1 VEGFR1 VEGFR-1 133 0.6 VEGF vascular endothelial growth factor VEGFR VEGF receptor sVEGFR-1 soluble VEGFR-1 svVEGF snake venom VEGF Tf svVEGF Trimeresurus flavoviridis svVEGF VPF 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140804 16104843 185170 23910 12680 VEGFA VEGF VEGF 137 10.4 factor VEGFR VEGF receptor sVEGFR-1 soluble VEGFR-1 svVEGF snake venom VEGF Tf svVEGF Trimeresurus flavoviridis svVEGF VPF vascular permeability factor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140805 16104843 185170 23910 12680 VEGFA VPF VPF 143 5.8 VEGFR-1 svVEGF snake venom VEGF Tf svVEGF Trimeresurus flavoviridis svVEGF VPF vascular permeability factor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140806 16104843 185172 23910 12680 VEGFA VEGF VEGF 1 10.4 The VEGF (vascular vascular endothelial growth factor family and its receptors are 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140807 16104843 185173 23910 12680 VEGFA VEGF VEGF 2 10.4 Currently the VEGF family consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140808 16104843 185173 23910 12680 VEGFA VEGF-A VEGF-A 6 7.6 Currently the VEGF family consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140809 16104843 185173 16459 8893 PGF PlGF PlGF 7 4.6 Currently the VEGF family consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and snake 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140810 16104843 185173 23911 12681 VEGFB VEGFB VEGF-B 11 1.8 VEGF family consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and snake venom VEGF 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140811 16104843 185173 23912 12682 VEGFC VEGFC VEGF-C 12 1.8 family consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and snake venom VEGF 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140812 16104843 185173 7579 3708 FIGF VEGF-D VEGF-D 13 1.3 consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and snake venom VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140813 16104843 185173 23910 12680 VEGFA VEGF VEGF 18 10.4 placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and snake venom VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140814 16104843 185174 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A has at least nine subtypes due to the alternative splicing 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140815 16104843 185175 23910 12680 VEGFA VEGF VEGF 2 10.4 Although the VEGF 165 isoform plays a central role in vascular development recent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140816 16104843 185175 23910 12680 VEGFA VEGF VEGF 18 10.4 role in vascular development recent studies have demonstrated that each VEGF isoform plays distinct roles in vascular patterning and arterial development 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140817 16104843 185176 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A binds to and activates two tyrosine kinase receptors VEGFR (VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140818 16104843 185176 10981 6307 KDR VEGFR VEGFR 9 3.3 VEGF-A binds to and activates two tyrosine kinase receptors VEGFR (VEGF VEGF receptor -1 and VEGFR-2 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140819 16104843 185176 23910 12680 VEGFA VEGF VEGF 10 10.4 binds to and activates two tyrosine kinase receptors VEGFR (VEGF VEGF receptor -1 and VEGFR-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140820 16104843 185176 10981 6307 KDR VEGFR2 VEGFR-2 13 4.3 two tyrosine kinase receptors VEGFR (VEGF VEGF receptor -1 and VEGFR-2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140821 16104843 185177 10981 6307 KDR VEGFR2 VEGFR-2 0 4.3 VEGFR-2 mediates most of the endothelial growth and survival signals but 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140822 16104843 185178 23910 12680 VEGFA VEGF-A VEGF-A 3 7.6 In solid tumours VEGF-A and its receptor are involved in carcinogenesis invasion and distant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140823 16104843 185179 23910 12680 VEGFA VEGF-A VEGF-A 0 7.6 VEGF-A also has a neuroprotective effect on hypoxic motor neurons and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140824 16104843 185179 20996 11179 SOD1 ALS ALS 15 1.0 effect on hypoxic motor neurons and is a modifier of ALS (amyotrophic amyotrophic lateral sclerosis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00117767640411015<>ScoreDetail__5468|IGFALS|0.000820142704830641__11179|SOD1|0.00117767640411015__ 0 0 0 0 0 140825 16104843 185180 23910 12680 VEGFA VEGF VEGF 10 10.4 progress in the molecular and biological understanding of the VEGF/VEGFR VEGF VEGFR system provides us with novel and promising therapeutic strategies 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 140826 16104843 185180 10981 6307 KDR VEGFR VEGFR 10 3.3 in the molecular and biological understanding of the VEGF/VEGFR VEGF VEGFR system provides us with novel and promising therapeutic strategies and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142213 16120782 186870 20996 11179 SOD1 ALS ALS 3 1.9 Amyotrophic lateral sclerosis (ALS) ALS represents a fatal neurodegenerative disorder characterized by progressive death of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142214 16120782 186872 17031 9232 PPARA PPAR PPAR 5 3.3 Because peroxisome proliferator-activated receptor gamma (PPAR PPAR gamma agonists act as potent anti-inflammatory drugs we tested whether 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142215 16120782 186872 20996 11179 SOD1 SOD1 SOD1 18 3.4 as potent anti-inflammatory drugs we tested whether superoxide dismutase (SOD1)-G93A SOD1 -G93A transgenic mice a mouse model of ALS benefit from 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142216 16120782 186872 20996 11179 SOD1 ALS ALS 25 1.9 dismutase (SOD1)-G93A SOD1 -G93A transgenic mice a mouse model of ALS benefit from oral treatment with the PPAR gamma agonist pioglitazone 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142217 16120782 186872 17031 9232 PPARA PPAR PPAR 32 3.3 mouse model of ALS benefit from oral treatment with the PPAR gamma agonist pioglitazone (Pio) Pio 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142218 16120782 186877 20996 11179 SOD1 SOD1 SOD1 27 3.4 whereas both the mRNA and protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142219 16120782 186877 20996 11179 SOD1 SOD1 SOD1 32 3.4 protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142220 16120782 186879 17031 9232 PPARA PPAR PPAR 4 3.3 Peroxisome proliferator-activated receptor gamma (PPAR PPAR gamma ligands were developed as oral antidiabetic drugs after the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142221 16120782 186879 17031 9232 PPARA PPAR PPAR 17 3.3 were developed as oral antidiabetic drugs after the discovery that PPAR gamma activation increases insulin sensitivity and normalizes serum glucose levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142222 16120782 186880 17031 9232 PPARA PPAR PPAR 8 3.3 Beyond their insulin sensitizing and other metabolic actions PPAR gamma ligands exert several other PPAR gamma-dependent and -independent antineoplastic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142223 16120782 186880 17031 9232 PPARA PPAR PPAR 14 3.3 and other metabolic actions PPAR gamma ligands exert several other PPAR gamma-dependent and -independent antineoplastic and anti-inflammatory effects (Daynes Daynes and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142224 16120782 186881 20996 11179 SOD1 ALS ALS 13 1.9 as Alzheimer's disease (AD) AD and amyotrophic lateral sclerosis (ALS), ALS are accompanied by an inflammatory component it has been hypothesized 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142225 16120782 186882 20996 11179 SOD1 ALS ALS 19 1.9 developed and tested in animal models and clinical trials of ALS and AD (Lim Lim et al. 2000 In t'Veld et 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142226 16120782 186882 16343 17468 PDLIM5 LIM Lim 22 0.8 animal models and clinical trials of ALS and AD (Lim Lim et al. 2000 In t'Veld et al. 2001 Drachman et 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 142227 16120782 186883 20996 11179 SOD1 ALS ALS 5 1.9 The primary pathological feature of ALS is the loss of motor neurons (Talbot, Talbot 2002 which 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142228 16120782 186883 17610 9605 PTGS2 COX-2 COX-2 37 2.0 astrocytes as well as the expression of cyclooxygenase 2 (COX-2) COX-2 and nitric oxide synthase (iNOS) iNOS in the spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142229 16120782 186883 14535 7873 NOS2A iNOS iNOS 42 2.2 of cyclooxygenase 2 (COX-2) COX-2 and nitric oxide synthase (iNOS) iNOS in the spinal cord (Phul Phul et al. 2000 Almer 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142230 16120782 186884 20996 11179 SOD1 SOD1 SOD1 25 3.4 human gene encoding for copper/zinc copper zinc superoxide dismutase (SOD1), SOD1 which have been linked to inherited ALS (Gurney Gurney et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142231 16120782 186884 20996 11179 SOD1 ALS ALS 32 1.9 superoxide dismutase (SOD1), SOD1 which have been linked to inherited ALS (Gurney Gurney et al. 1994 Hensley et al. 2002 Yoshihara 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142232 16120782 186885 20996 11179 SOD1 SOD1 SOD1 17 3.4 astrocytes already at an early presymptomatic stage of disease in SOD1 transgenic mice suggests that inflammation may contribute to motor neuron 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142233 16120782 186886 17031 9232 PPARA PPAR PPAR 4 3.3 In microglia and macrophages PPAR gamma activation results in inhibition of proinflammatory gene expression through 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142234 16120782 186886 926 620 APP amyloid amyloid 24 1.3 various mechanisms (Landreth Landreth and Heneka 2001 gamma agonists reduce amyloid beta peptide and cytokine mediated neuroinflammation and neurotoxicity in vitro 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 142235 16120782 186887 20996 11179 SOD1 SOD1 SOD1 15 3.4 in these studies we tested whether an oral treatment of SOD1 transgenic mice with the PPAR gamma agonist pioglitazone would reduce 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142236 16120782 186887 17031 9232 PPARA PPAR PPAR 20 3.3 whether an oral treatment of SOD1 transgenic mice with the PPAR gamma agonist pioglitazone would reduce neuroinflammation protect from motor neuron 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142237 16120782 186887 20996 11179 SOD1 ALS ALS 35 1.9 reduce neuroinflammation protect from motor neuron loss and improve clinical ALS symptoms 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142238 16120782 186889 20996 11179 SOD1 SOD1 SOD1 15 3.4 (The The Jackson Laboratory Bar Harbor ME which harbor human SOD1 with the G93A mutation in high copy number were used 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142239 16120782 186898 20996 11179 SOD1 SOD1 SOD1 29 3.4 ( n = 18 for wt n = 13 for SOD1 and nontreated ( n = 17 for wt n = 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142240 16120782 186898 20996 11179 SOD1 SOD1 SOD1 42 3.4 ( n = 17 for wt n = 22 for SOD1 groups 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142241 16120782 186909 20996 11179 SOD1 SOD1 SOD1 30 3.4 wt n = 13 for wt-Pio n = 10 for SOD1 n = 7 for SOD1-Pio 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142242 16120782 186918 19305 10489 S100A12 CGRP CGRP 8 1.3 Sections were then stained for calcitonin gene-related peptide (CGRP) CGRP immunoreactivity essentially as described in detail previously (Schutz Schutz et 1 JUMiner_v2.2 1 2 calcitonin gene-related peptide 0 2 10489 TotalCon:2<>10489|S100A12|6283|Complete__1437|CALCA|796|Complete__<>AvaiableGeneRif=2<>BEST:10489|S100A12|0.000449019781345252<>ScoreDetail__1437|CALCA|0.000385381921135833__10489|S100A12|0.000449019781345252__ 0 0 0 0 0 142243 16120782 186919 19305 10489 S100A12 CGRP CGRP-positive 6 1.3 For the quantification of motor neurons CGRP-positive cell bodies were counted on six sections per animal and 1 JUMiner_v2.2 1 2 calcitonin gene-related peptide 0 2 10489 TotalCon:2<>10489|S100A12|6283|Complete__1437|CALCA|796|Complete__<>AvaiableGeneRif=2<>BEST:10489|S100A12|0.000449019781345252<>ScoreDetail__1437|CALCA|0.000385381921135833__10489|S100A12|0.000449019781345252__ 0 0 0 0 0 142244 16120782 186921 10731 6149 ITGAM CD11b CD11b 15 1.0 performed by staining with a rat monoclonal antibody against murine CD11b (diluted diluted 1 250 catalog #MCA711 Serotec D_amp_uuml sseldorf Germany 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142245 16120782 186931 20996 11179 SOD1 SOD1 SOD1 36 3.4 wt n = 4 for wt-Pio n = 4 for SOD1 n = 5 for SOD1-Pio 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142246 16120782 186933 19254 10472 RUNX2 CCD CCD 26 0.3 a Nikon (D_amp_uuml;sseldorf, D_amp_uuml sseldorf Germany H800 microscope with a CCD camera (DXP-9100P DXP-9100P 3CCD color video Sony Tokyo Japan and 1 JUMiner_v2.2 1 2 ccd camera 0 0 0 0 0 0 0 0 142247 16120782 186933 16343 17468 PDLIM5 LIM LIM 40 0.8 video Sony Tokyo Japan and using Lucia imaging software (LIM LIM Laboratory Imaging distributed by Nikon 1 JUMiner_v2.2 1 2 lim et al 0 0 0 0 0 0 0 0 142248 16120782 186936 19573 10691 SDS SDS SDS 23 0.0 radioimmunoprecipitation assay buffer (1% 1% Triton 1% sodium deoxycholate 0.1% SDS 150 m M NaCl 50 m M Tris-HCl pH 7.2 1 JUMiner_v2.2 1 0 0 2 19440 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:19440|SBDS|0.000302519680639415<>ScoreDetail__10691|SDS|6.84041316095492e-05__19440|SBDS|0.000302519680639415__ 0 0 0 0 0 142249 16120782 186937 14535 7873 NOS2A iNOS iNOS 4 2.2 For the analysis of iNOS and COX-2 100 microg of protein samples was separated in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142250 16120782 186937 17610 9605 PTGS2 COX-2 COX-2 6 2.0 For the analysis of iNOS and COX-2 100 microg of protein samples was separated in 10% SDS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142251 16120782 186937 14535 7873 NOS2A iNOS iNOS 29 2.2 onto Immobilon-P polyvinylidene difluoride membranes and stained with a polyclonal iNOS antibody at 1 500 dilution (rabbit rabbit polyclonal antibody to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142252 16120782 186937 14535 7873 NOS2A iNOS iNOS 42 2.2 dilution (rabbit rabbit polyclonal antibody to C terminus of murine iNOS Santa Cruz Biotechology Heidelberg Germany or a polyclonal COX-2 antibody 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142253 16120782 186937 17610 9605 PTGS2 COX-2 COX-2 51 2.0 murine iNOS Santa Cruz Biotechology Heidelberg Germany or a polyclonal COX-2 antibody at a 1 600 dilution (rabbit rabbit polyclonal antibody 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142254 16120782 186937 17610 9605 PTGS2 COX-2 COX-2 65 2.0 dilution (rabbit rabbit polyclonal antibody to synthetic peptide from murine COX-2 Cayman Ann Arbor MI 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142255 16120782 186937 19573 10691 SDS SDS SDS 16 0.0 COX-2 100 microg of protein samples was separated in 10% SDS gels transferred onto Immobilon-P polyvinylidene difluoride membranes and stained with 1 JUMiner_v2.2 1 0 0 2 19440 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:19440|SBDS|0.000302519680639415<>ScoreDetail__10691|SDS|6.84041316095492e-05__19440|SBDS|0.000302519680639415__ 0 0 0 0 0 142256 16120782 186938 14535 7873 NOS2A iNOS iNOS 4 2.2 The specificities of the iNOS and COX-2 antibodies have been confirmed by positive controls containing 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142257 16120782 186938 17610 9605 PTGS2 COX-2 COX-2 6 2.0 The specificities of the iNOS and COX-2 antibodies have been confirmed by positive controls containing iNOS or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142258 16120782 186938 14535 7873 NOS2A iNOS iNOS 15 2.2 and COX-2 antibodies have been confirmed by positive controls containing iNOS or COX-2 protein (data data not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142259 16120782 186938 17610 9605 PTGS2 COX-2 COX-2 17 2.0 antibodies have been confirmed by positive controls containing iNOS or COX-2 protein (data data not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142260 16120782 186939 20996 11179 SOD1 SOD1 SOD1 7 3.4 For the analysis of human and mouse SOD1 2 microg of protein samples was separated in 15% SDS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142261 16120782 186939 20996 11179 SOD1 SOD1 SOD1 30 3.4 onto nitrocellulose membranes and stained with a rabbit polyclonal anti-human SOD1 antibody at 1 5000 dilution (SOD-100; SOD-100 Stressgen Victoria British 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142262 16120782 186939 20996 11179 SOD1 SOD1 SOD1 46 3.4 Stressgen Victoria British Colombia Canada or a rabbit polyclonal anti-mouse SOD1 antibody at 1 5000 dilution (SOD-101; SOD-101 Stressgen 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142263 16120782 186939 19573 10691 SDS SDS SDS 17 0.0 SOD1 2 microg of protein samples was separated in 15% SDS gels transferred onto nitrocellulose membranes and stained with a rabbit 1 JUMiner_v2.2 1 0 0 2 19440 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:19440|SBDS|0.000302519680639415<>ScoreDetail__10691|SDS|6.84041316095492e-05__19440|SBDS|0.000302519680639415__ 0 0 0 0 0 142264 16120782 186941 20996 11179 SOD1 SOD1 SOD1 6 3.4 The SOD-101 antibody predominantly detected mouse SOD1 but in addition showed minimal cross-reactivity with human SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142265 16120782 186941 20996 11179 SOD1 SOD1 SOD1 15 3.4 mouse SOD1 but in addition showed minimal cross-reactivity with human SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142266 16120782 186946 4413 1984 CISH SOCS SOCS 9 1.6 The primers were the following suppressor of cytokine signaling (SOCS)-1, SOCS -1 forward 5'-AGC-AGC-TCG-AAA-AGG-CAG-TC-3' and reverse 5'-ACA-CTC-ACT-TCC-GCA-CCT-TC-3' SOCS-3 forward 5'-ACC-AGC-GCC-ACT-TCT-TCA-CG-3' and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142267 16120782 186946 20991 19391 SOCS3 SOCS-3 SOCS-3 15 3.5 cytokine signaling (SOCS)-1, SOCS -1 forward 5'-AGC-AGC-TCG-AAA-AGG-CAG-TC-3' and reverse 5'-ACA-CTC-ACT-TCC-GCA-CCT-TC-3' SOCS-3 forward 5'-ACC-AGC-GCC-ACT-TCT-TCA-CG-3' and reverse 5'-GTG-GAG-CAT-CAT-ACT-GAT-CC-3' mouse SOD1 forward 5'-GTC-CGT-CGG-CTT-CTC-GTC-T-3' and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142268 16120782 186946 20996 11179 SOD1 SOD1 SOD1 22 3.4 and reverse 5'-ACA-CTC-ACT-TCC-GCA-CCT-TC-3' SOCS-3 forward 5'-ACC-AGC-GCC-ACT-TCT-TCA-CG-3' and reverse 5'-GTG-GAG-CAT-CAT-ACT-GAT-CC-3' mouse SOD1 forward 5'-GTC-CGT-CGG-CTT-CTC-GTC-T-3' and reverse 5'-CAC-AAC-TGG-TTC-ACC-GCT-TG-3' human SOD1 forward 5'-TGG-TTT-GCG-TCG-TAG-TCT-CCT-3' and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142269 16120782 186946 20996 11179 SOD1 SOD1 SOD1 29 3.4 reverse 5'-GTG-GAG-CAT-CAT-ACT-GAT-CC-3' mouse SOD1 forward 5'-GTC-CGT-CGG-CTT-CTC-GTC-T-3' and reverse 5'-CAC-AAC-TGG-TTC-ACC-GCT-TG-3' human SOD1 forward 5'-TGG-TTT-GCG-TCG-TAG-TCT-CCT-3' and reverse 5'-AAT-GCT-TCC-CCA-CAC-CTT-CA-3' 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142270 16120782 186947 20987 19383 SOCS1 SOCS-1 SOCS-1 13 3.5 5'-TCA-CCA-GGG-CTG-CCA-TTT-GC-3' and reverse 5'-GAC-TCC-ACG-ACA-TAC-TCA-GC-3' were used as housekeeping control for SOCS-1 and 3 beta-actin forward 5'-CAC-AGC-TTC-TTT-GCA-GCT-CCT-T-3' and reverse 5'-TCA-GGA-TAC-CTC-TCT-TGC-TCT-GG-3' were used 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142271 16120782 186947 20991 19391 SOCS3 SOCS-3 SOCS-3 13 3.5 5'-TCA-CCA-GGG-CTG-CCA-TTT-GC-3' and reverse 5'-GAC-TCC-ACG-ACA-TAC-TCA-GC-3' were used as housekeeping control for SOCS-1 and 3 beta-actin forward 5'-CAC-AGC-TTC-TTT-GCA-GCT-CCT-T-3' and reverse 5'-TCA-GGA-TAC-CTC-TCT-TGC-TCT-GG-3' were used 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142272 16120782 186947 211 132 ACTB beta-actin beta-actin 16 0.3 5'-GAC-TCC-ACG-ACA-TAC-TCA-GC-3' were used as housekeeping control for SOCS-1 and 3 beta-actin forward 5'-CAC-AGC-TTC-TTT-GCA-GCT-CCT-T-3' and reverse 5'-TCA-GGA-TAC-CTC-TCT-TGC-TCT-GG-3' were used as housekeeping control 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142273 16120782 186947 20996 11179 SOD1 SOD1 SOD1 31 3.4 5'-TCA-GGA-TAC-CTC-TCT-TGC-TCT-GG-3' were used as housekeeping control for mouse and human SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142274 16120782 186948 4413 1984 CISH SOCS SOCS 3 1.6 PCR conditions for SOCS PCR were 32 cycles of denaturation at 95degreeC for 30 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142275 16120782 186948 16033 8600 PANX2 PX2 PX2 30 0.0 s and extension at 72degreeC for 45 s using a PX2 thermocycler (ThermoHybaid, ThermoHybaid Ulm Germany 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142276 16120782 186950 20996 11179 SOD1 SOD1 SOD1 1 3.4 The SOD1 PCRs were performed using a SYBR Green Jump Start Taq 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142277 16120782 186955 4413 1984 CISH SOCS SOCS 3 1.6 Western blot and SOCS RT-PCR experiments were quantified by determination of band intensities using 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142278 16120782 186957 20996 11179 SOD1 SOD1 SOD1 11 3.4 the calculation of the relative abundancies of mouse and human SOD1 transcripts the differences in C T between beta-actin and SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142279 16120782 186957 211 132 ACTB beta-actin beta-actin 19 0.3 and human SOD1 transcripts the differences in C T between beta-actin and SOD1 were determined and expressed as x -fold difference 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142280 16120782 186957 20996 11179 SOD1 SOD1 SOD1 21 3.4 SOD1 transcripts the differences in C T between beta-actin and SOD1 were determined and expressed as x -fold difference from beta-actin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142281 16120782 186957 211 132 ACTB beta-actin beta-actin 31 0.3 SOD1 were determined and expressed as x -fold difference from beta-actin expression using the following equation 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142282 16120782 186977 17031 9232 PPARA PPAR PPAR 0 3.3 PPAR gamma ligands suppress microglial activation thereby protecting neurons from inflammation-mediated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142283 16120782 186978 17610 9605 PTGS2 COX-2 COX-2 2 2.0 Coinduction of COX-2 and iNOS were described in several neurodegenerative disorders including ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142284 16120782 186978 14535 7873 NOS2A iNOS iNOS 4 2.2 Coinduction of COX-2 and iNOS were described in several neurodegenerative disorders including ALS as well 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142285 16120782 186978 20996 11179 SOD1 ALS ALS 12 1.9 COX-2 and iNOS were described in several neurodegenerative disorders including ALS as well as in the SOD1-G93A model used in this 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142286 16120782 186979 17610 9605 PTGS2 COX-2 COX-2 12 2.0 analysis of lumbar spinal cord lysates from 90-d-old mice confirmed COX-2 expression in wild-type mice ( n = 4 and revealed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142287 16120782 186979 17610 9605 PTGS2 COX-2 COX-2 32 2.0 revealed that SOD1-G93A mice ( n = 4 showed elevated COX-2 levels ( Fig 3 b 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142288 16120782 186980 14535 7873 NOS2A iNOS iNOS 2 2.2 In contrast iNOS was hardly detectable in wild-type but strongly expressed by SOD1-G93A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142289 16120782 186981 17610 9605 PTGS2 COX-2 COX-2 7 2.0 In both cases Pio treatment significantly decreased COX-2 and iNOS expression in SOD1-G93A mice ( n = 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142290 16120782 186981 14535 7873 NOS2A iNOS iNOS 9 2.2 In both cases Pio treatment significantly decreased COX-2 and iNOS expression in SOD1-G93A mice ( n = 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142291 16120782 186982 20987 19383 SOCS1 SOCS-1 SOCS-1 12 3.5 reduction was paralleled by a marked transcriptional upregulation of anti-inflammatory SOCS-1 and SOCS-3 genes ( Fig 3 c in both Pio-treated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142292 16120782 186982 20991 19391 SOCS3 SOCS-3 SOCS-3 12 3.5 reduction was paralleled by a marked transcriptional upregulation of anti-inflammatory SOCS-1 and SOCS-3 genes ( Fig 3 c in both Pio-treated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142293 16120782 186982 20991 19391 SOCS3 SOCS-3 SOCS-3 14 3.5 paralleled by a marked transcriptional upregulation of anti-inflammatory SOCS-1 and SOCS-3 genes ( Fig 3 c in both Pio-treated groups ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142294 16120782 186983 20996 11179 SOD1 ALS ALS 0 1.9 ALS is a fatal neurodegenerative disease without curative treatment options to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142295 16120782 186985 20996 11179 SOD1 ALS ALS 13 1.9 including excitotoxic apoptotic and metabolic mechanisms have been implied in ALS pathogenesis and proposed as therapeutic targets (Talbot, Talbot 2002 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142296 16120782 186987 17031 9232 PPARA PPAR PPAR 0 3.3 PPAR gamma and neuroinflammation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142297 16120782 186988 20996 11179 SOD1 ALS ALS 35 1.9 radicals may significantly contribute to the development and progression of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142298 16120782 186989 17031 9232 PPARA PPAR PPAR 7 3.3 Originally developed as oral antidiabetics agonists of PPAR gamma have been found to exert potent anti-inflammatory effects in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142299 16120782 186989 17031 9232 PPARA PPAR PPAR 45 3.3 SOD1-G93A transgenic mice would benefit from chronic treatment with a PPAR gamma agonist Within the thiazolidinedione class of PPAR gamma agonists 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142300 16120782 186989 17031 9232 PPARA PPAR PPAR 53 3.3 with a PPAR gamma agonist Within the thiazolidinedione class of PPAR gamma agonists Pio is the only substance that penetrates the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142301 16120782 186990 20996 11179 SOD1 ALS ALS 16 1.9 suppression of inflammation may offer a new therapeutic avenue in ALS treatment as supported by previous findings in animal models of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142302 16120782 186991 17031 9232 PPARA PPAR PPAR 0 3.3 PPAR gamma and microglial activation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142303 16120782 186999 20996 11179 SOD1 SOD1 SOD1 21 3.4 in SOD1-G93A mice a Probability of survival in nontreated (SOD1; SOD1 n = 10 compared with Pio-treated (SOD1-Pio; SOD1-Pio n = 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142304 16120782 187000 20996 11179 SOD1 SOD1 SOD1 34 3.4 wt-Pio n = 13 wild-type mice compared with their respective SOD1 and SOD1-Pio mice p _lt_ 0.05 p _lt_ 0.01 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142305 16120782 187000 20996 11179 SOD1 SOD1 SOD1 61 3.4 c Probability of onset of motor dysfunctions in nontreated (SOD1) SOD1 compared with Pio-treated (SOD1-Pio) SOD1-Pio mice d Time course of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142306 16120782 187000 20996 11179 SOD1 SOD1 SOD1 85 3.4 the paw grip endurance test p _lt_ 0.001 compared with SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142307 16120782 187002 19305 10489 S100A12 CGRP CGRP-positive 14 1.3 treatment on motor neuron degeneration and muscle fiber morphology a CGRP-positive motor neuron numbers in the lumbar spinal cord ( n 1 JUMiner_v2.2 1 2 calcitonin gene-related peptide 0 2 10489 TotalCon:2<>10489|S100A12|6283|Complete__1437|CALCA|796|Complete__<>AvaiableGeneRif=2<>BEST:10489|S100A12|0.000449019781345252<>ScoreDetail__1437|CALCA|0.000385381921135833__10489|S100A12|0.000449019781345252__ 0 0 0 0 0 142308 16120782 187002 20996 11179 SOD1 SOD1 SOD1 34 3.4 n = 5 for wild-type group n = 6 for SOD1 groups and median fiber diameters in the quadriceps muscle ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142309 16120782 187002 20996 11179 SOD1 SOD1 SOD1 59 3.4 wt n = 4 for wt-Pio n = 4 for SOD1 n = 5 for SOD1-Pio at day 90 of life 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142310 16120782 187002 20996 11179 SOD1 SOD1 SOD1 80 3.4 p _lt_ 0.05 and p _lt_ 0.01 compared with Pio-treated SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142311 16120782 187003 19305 10489 S100A12 CGRP CGRP 4 1.3 Error bars represent SEM (CGRP CGRP cells or SD (median median fiber diameter b Evaluation of 1 JUMiner_v2.2 1 2 32 0 2 10489 TotalCon:2<>10489|S100A12|6283|Complete__1437|CALCA|796|Complete__<>AvaiableGeneRif=2<>BEST:10489|S100A12|0.000449019781345252<>ScoreDetail__1437|CALCA|0.000385381921135833__10489|S100A12|0.000449019781345252__ 0 0 0 0 0 142312 16120782 187003 19305 10489 S100A12 CGRP CGRP 22 1.3 b Evaluation of the spinal cord motor neuron area by CGRP immunohistochemistry and muscle fiber morphology by histological HE stain 1 JUMiner_v2.2 1 2 calcitonin gene-related peptide 0 2 10489 TotalCon:2<>10489|S100A12|6283|Complete__1437|CALCA|796|Complete__<>AvaiableGeneRif=2<>BEST:10489|S100A12|0.000449019781345252<>ScoreDetail__1437|CALCA|0.000385381921135833__10489|S100A12|0.000449019781345252__ 0 0 0 0 0 142313 16120782 187005 10731 6149 ITGAM CD11b CD11b 17 1.0 activation of astroglia and inflammation markers a Immunofluorescence colabeling of CD11b (green) green and CGRP (red) red in the spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142314 16120782 187005 19305 10489 S100A12 CGRP CGRP 20 1.3 inflammation markers a Immunofluorescence colabeling of CD11b (green) green and CGRP (red) red in the spinal cord motor neuron area at 1 JUMiner_v2.2 1 2 calcitonin gene-related peptide 0 2 10489 TotalCon:2<>10489|S100A12|6283|Complete__1437|CALCA|796|Complete__<>AvaiableGeneRif=2<>BEST:10489|S100A12|0.000449019781345252<>ScoreDetail__1437|CALCA|0.000385381921135833__10489|S100A12|0.000449019781345252__ 0 0 0 0 0 142315 16120782 187006 10731 6149 ITGAM CD11b CD11b 16 1.0 by bright-field (blue/black blue black reaction products and green fluorescent CD11b immunohistochemistry (bottom bottom left are shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142316 16120782 187007 20996 11179 SOD1 SOD1 SOD1 21 3.4 = 4 for wt and wt-Pio n = 5 for SOD1 and SOD1-Pio and of COX-2 and iNOS Western blots ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142317 16120782 187007 17610 9605 PTGS2 COX-2 COX-2 26 2.0 wt-Pio n = 5 for SOD1 and SOD1-Pio and of COX-2 and iNOS Western blots ( n = 4 for all 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142318 16120782 187007 14535 7873 NOS2A iNOS iNOS 28 2.2 = 5 for SOD1 and SOD1-Pio and of COX-2 and iNOS Western blots ( n = 4 for all groups from 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142319 16120782 187007 20987 19383 SOCS1 SOCS-1 SOCS-1 68 3.5 0.001 compared with the respective nontreated group c Quantification of SOCS-1 and SOCS-3 mRNA levels in the spinal cord at day 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142320 16120782 187007 20991 19391 SOCS3 SOCS-3 SOCS-3 68 3.5 0.001 compared with the respective nontreated group c Quantification of SOCS-1 and SOCS-3 mRNA levels in the spinal cord at day 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142321 16120782 187007 20991 19391 SOCS3 SOCS-3 SOCS-3 70 3.5 with the respective nontreated group c Quantification of SOCS-1 and SOCS-3 mRNA levels in the spinal cord at day 90 of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142322 16120782 187008 20996 11179 SOD1 SOD1 SOD1 15 3.4 per group are shown p _lt_ 0.001 compared with nontreated SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142323 16120782 187011 20996 11179 SOD1 SOD1 SOD1 12 3.4 pioglitazone treatment on the expression levels of endogenous and transgenic SOD1 a -d Quantification of mouse SOD1 ( a and human 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142324 16120782 187011 20996 11179 SOD1 SOD1 SOD1 19 3.4 of endogenous and transgenic SOD1 a -d Quantification of mouse SOD1 ( a and human SOD1 ( b mRNA expression levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142325 16120782 187011 20996 11179 SOD1 SOD1 SOD1 25 3.4 a -d Quantification of mouse SOD1 ( a and human SOD1 ( b mRNA expression levels and of mouse SOD1 ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142326 16120782 187011 20996 11179 SOD1 SOD1 SOD1 35 3.4 human SOD1 ( b mRNA expression levels and of mouse SOD1 ( c and human SOD1 ( d protein levels in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142327 16120782 187011 20996 11179 SOD1 SOD1 SOD1 41 3.4 expression levels and of mouse SOD1 ( c and human SOD1 ( d protein levels in the spinal cord at day 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142328 16120782 187012 20996 11179 SOD1 SOD1 SOD1 5 3.4 Note the variations in mouse SOD1 expression levels between the groups in a and c 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142329 16120782 187014 20996 11179 SOD1 SOD1 SOD1 11 3.4 treatment does not alter expression levels of endogenous and transgenic SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142330 16120782 187015 20996 11179 SOD1 SOD1 SOD1 7 3.4 Because the expression level of the mutant SOD1 transgene affects the course of disease in SOD1-G93A mice and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142331 16120782 187015 20996 11179 SOD1 SOD1 SOD1 39 3.4 an altered expression of either endogenous mouse or transgenic human SOD1 we determined SOD1 gene expression levels in our mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142332 16120782 187015 20996 11179 SOD1 SOD1 SOD1 42 3.4 of either endogenous mouse or transgenic human SOD1 we determined SOD1 gene expression levels in our mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142333 16120782 187016 20996 11179 SOD1 SOD1 SOD1 26 3.4 for total RNA and protein and both mouse and human SOD1 expression levels were determined using quantitative RT-PCR and Western blotting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142334 16120782 187017 20996 11179 SOD1 SOD1 SOD1 8 3.4 As shown in Figure 4 neither mouse SOD1 mRNA ( Fig 4 a or protein ( Fig 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142335 16120782 187017 20996 11179 SOD1 SOD1 SOD1 25 3.4 a or protein ( Fig 4 c levels nor human SOD1 mRNA ( Fig 4 b or protein ( Fig 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142336 16120782 187018 17031 9232 PPARA PPAR PPAR 0 3.3 PPAR gamma-mediated inhibition of inflammatory mediators 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142337 16120782 187019 17610 9605 PTGS2 COX-2 COX-2 9 2.0 We found a marked reduction in the expression of COX-2 and iNOS two major proinflammatory enzymes after Pio treatment 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142338 16120782 187019 14535 7873 NOS2A iNOS iNOS 11 2.2 found a marked reduction in the expression of COX-2 and iNOS two major proinflammatory enzymes after Pio treatment 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142339 16120782 187020 17610 9605 PTGS2 COX-2 COX-2 28 2.0 by similar or identical stimulators (O'Banion, O'Banion 1999 because the COX-2 and iNOS promoters share several binding sites for signal transduction 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142340 16120782 187020 14535 7873 NOS2A iNOS iNOS 30 2.2 or identical stimulators (O'Banion, O'Banion 1999 because the COX-2 and iNOS promoters share several binding sites for signal transduction factors involved 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142341 16120782 187021 14535 7873 NOS2A iNOS iNOS-derived 7 2.2 Apart from the detrimental action of either iNOS-derived excess NO or COX-2-generated proinflammatory prostanoids the dual inhibition of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142342 16120782 187021 17610 9605 PTGS2 COX COX-2-generated 11 0.0 from the detrimental action of either iNOS-derived excess NO or COX-2-generated proinflammatory prostanoids the dual inhibition of both enzymes observed in 11 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 142343 16120782 187022 17610 9605 PTGS2 COX-2 COX-2 8 2.0 Thus NO may increase the catalytic activity of COX-2 thereby increasing the production of proinflammatory prostanoids (Nogawa Nogawa et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142344 16120782 187024 17031 9232 PPARA PPAR PPAR 0 3.3 PPAR gamma-mediated activation of anti-inflammatory genes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142345 16120782 187025 17031 9232 PPARA PPAR PPAR 1 3.3 Several PPAR gamma-dependent and -independent anti-inflammatory actions of the TZD class of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142346 16120782 187026 20987 19383 SOCS1 SOCS-1 SOCS-1 1 3.5 Interestingly SOCS-1 and SOCS-3 have been reported to increase in response to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142347 16120782 187026 20991 19391 SOCS3 SOCS-3 SOCS-3 1 3.5 Interestingly SOCS-1 and SOCS-3 have been reported to increase in response to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142348 16120782 187026 20991 19391 SOCS3 SOCS-3 SOCS-3 3 3.5 Interestingly SOCS-1 and SOCS-3 have been reported to increase in response to TZDs in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142349 16120782 187027 14535 7873 NOS2A iNOS iNOS 10 2.2 The latter signal transduction pathway is also involved in the iNOS and COX-2 gene regulation after inflammatory stimulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142350 16120782 187027 17610 9605 PTGS2 COX-2 COX-2 12 2.0 signal transduction pathway is also involved in the iNOS and COX-2 gene regulation after inflammatory stimulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142351 16120782 187028 20987 19383 SOCS1 SOCS-1 SOCS-1 4 3.5 Because the ability of SOCS-1 and SOCS-3 to suppress cytokine stimulation has also been confirmed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142352 16120782 187028 20991 19391 SOCS3 SOCS-3 SOCS-3 4 3.5 Because the ability of SOCS-1 and SOCS-3 to suppress cytokine stimulation has also been confirmed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142353 16120782 187028 20991 19391 SOCS3 SOCS-3 SOCS-3 6 3.5 Because the ability of SOCS-1 and SOCS-3 to suppress cytokine stimulation has also been confirmed by in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142354 16120782 187028 20987 19383 SOCS1 SOCS-1 SOCS-1 38 3.5 Suzuki et al. 2001 it seems likely that upregulation of SOCS-1 and SOCS-3 levels in response to Pio treatment reflects one 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142355 16120782 187028 20991 19391 SOCS3 SOCS-3 SOCS-3 38 3.5 Suzuki et al. 2001 it seems likely that upregulation of SOCS-1 and SOCS-3 levels in response to Pio treatment reflects one 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142356 16120782 187028 20991 19391 SOCS3 SOCS-3 SOCS-3 40 3.5 al. 2001 it seems likely that upregulation of SOCS-1 and SOCS-3 levels in response to Pio treatment reflects one mechanism of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142357 16120782 187028 14535 7873 NOS2A iNOS iNOS 66 2.2 antagonizing the JAK-STAT pathway contributes to the observed suppression of iNOS and COX-2 expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142358 16120782 187028 17610 9605 PTGS2 COX-2 COX-2 68 2.0 JAK-STAT pathway contributes to the observed suppression of iNOS and COX-2 expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142359 16120782 187030 17031 9232 PPARA PPAR PPAR 5 3.3 The principal clinical usage of PPAR gamma agonists is for treatment of type II diabetes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142360 16120782 187032 17031 9232 PPARA PPAR PPAR 6 3.3 It has been shown recently that PPAR gamma agonist treatment leads to an upregulation of Cu/Zn-SOD1 Cu 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142361 16120782 187032 20996 11179 SOD1 SOD1 SOD1 31 3.4 of ischemia (Shimazu Shimazu et al. 2005 suggesting that enhanced SOD1 levels may be protective by reducing oxidative stress 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142362 16120782 187033 20996 11179 SOD1 SOD1 SOD1 14 3.4 changes in the expression levels of neither mouse nor human SOD1 in our mice we can rule out that the reported 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142363 16120782 187033 20996 11179 SOD1 SOD1 SOD1 34 3.4 reported effects of chronic Pio treatment result from altered endogenous SOD1 or transgenic SOD1-G93A expression levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142364 16120782 187034 20996 11179 SOD1 ALS ALS 4 1.9 Antiinflammatory treatment strategies in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142365 16120782 187035 20996 11179 SOD1 ALS ALS 22 1.9 significantly contributes to the progression of motor neuron death in ALS has been supported by studies on SOD1 transgenic mice reporting 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142366 16120782 187035 20996 11179 SOD1 SOD1 SOD1 29 3.4 neuron death in ALS has been supported by studies on SOD1 transgenic mice reporting protective effects of cyclooxygenase inhibitors (Drachman Drachman 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142367 16120782 187038 20996 11179 SOD1 ALS ALS 29 1.9 not allow us to conclude that patients suffering from sporadic ALS will benefit from PPAR gamma-agonist treatment if initiated after clinical 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142368 16120782 187038 17031 9232 PPARA PPAR PPAR 33 3.3 conclude that patients suffering from sporadic ALS will benefit from PPAR gamma-agonist treatment if initiated after clinical onset of disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142369 16120782 187039 20996 11179 SOD1 ALS ALS 10 1.9 However it seems possible that in the case of familiar ALS family members with an inherited ALS risk which can be 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142370 16120782 187039 20996 11179 SOD1 ALS ALS 16 1.9 the case of familiar ALS family members with an inherited ALS risk which can be diagnosed before the appearance of clinical 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142371 16120782 187039 17031 9232 PPARA PPAR PPAR 32 3.3 before the appearance of clinical symptoms may benefit from prophylactic PPAR gamma-agonist medication 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142372 16120782 187040 20996 11179 SOD1 ALS ALS 29 1.9 they would be available readily for clinical trials in human ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00102919223206476<>ScoreDetail__5468|IGFALS|0.000491297024143739__11179|SOD1|0.00102919223206476__ 0 0 0 0 0 142373 16120782 187045 19305 10489 S100A12 CGRP CGRP 26 1.3 Nyberg (Uppsala, Uppsala Sweden for the generous gift of the CGRP antibody and Dr Albrecht Clement (Mainz, Mainz Germany for donating 1 JUMiner_v2.2 1 2 calcitonin gene-related peptide 0 2 10489 TotalCon:2<>10489|S100A12|6283|Complete__1437|CALCA|796|Complete__<>AvaiableGeneRif=2<>BEST:10489|S100A12|0.000449019781345252<>ScoreDetail__1437|CALCA|0.000385381921135833__10489|S100A12|0.000449019781345252__ 0 0 0 0 0 142374 16120782 187045 20996 11179 SOD1 SOD1 SOD1 36 3.4 antibody and Dr Albrecht Clement (Mainz, Mainz Germany for donating SOD1 antibodies 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 142375 16120782 187045 10290 5825 IGKV3D-20 A11 A11 0 0.0 (SFB400/A11), SFB400 A11 and by Grant DA016768 from the National Institutes of Health 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131175 16179515 172932 20996 11179 SOD1 SOD1 SOD1 8 1.7 Effect of neuroprotective drugs on gene expression in G93A/SOD1 G93A SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131176 16179515 172934 20996 11179 SOD1 SOD1 SOD1 15 1.7 this approach to identify molecular abnormalities in the G93A/SOD1 G93A SOD1 mouse an animal model of amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131177 16179515 172934 20996 11179 SOD1 ALS ALS 24 1.7 SOD1 mouse an animal model of amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00139723958710624<>ScoreDetail__5468|IGFALS|0.000612915807655876__11179|SOD1|0.00139723958710624__ 0 0 0 0 0 131178 16179515 172939 20996 11179 SOD1 SOD1 SOD1 8 1.7 That is we asked whether administration to the G93A/SOD1 G93A SOD1 mice of any of these drugs could reverse the alterations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131179 16179515 172942 20996 11179 SOD1 SOD1 SOD1 12 1.7 3 genes unaffected by the presence of the G93A/SOD1 G93A SOD1 mutation glial fibrillary acidic protein (GFAP), GFAP stroma-derived factor-1 (SDF-1), 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131180 16179515 172942 8254 4235 GFAP GFAP GFAP 18 2.5 the G93A/SOD1 G93A SOD1 mutation glial fibrillary acidic protein (GFAP), GFAP stroma-derived factor-1 (SDF-1), SDF-1 and excitatory amino acid transporter-2 (EAAT2) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131181 16179515 172942 20017 10940 SLC1A2 EAAT2 EAAT2 27 1.0 stroma-derived factor-1 (SDF-1), SDF-1 and excitatory amino acid transporter-2 (EAAT2) EAAT2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131182 16179515 172942 5200 10672 CXCL12 SDF1 SDF-1 21 0.0 mutation glial fibrillary acidic protein (GFAP), GFAP stroma-derived factor-1 (SDF-1), SDF-1 and excitatory amino acid transporter-2 (EAAT2) EAAT2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131183 16179515 172944 3901 1693 CD68 CD68 CD68 19 0.3 with anti-inflammatory and numerous other effects downregulated the microglia markers CD68 CD80 and CD86 all of which were upregulated in untreated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131184 16179515 172944 3908 1700 CD80 CD80 CD80 20 0.3 anti-inflammatory and numerous other effects downregulated the microglia markers CD68 CD80 and CD86 all of which were upregulated in untreated mutant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131185 16179515 172944 3914 1705 CD86 CD86 CD86 20 0.3 anti-inflammatory and numerous other effects downregulated the microglia markers CD68 CD80 and CD86 all of which were upregulated in untreated mutant 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131186 16179515 172944 3914 1705 CD86 CD86 CD86 22 0.3 numerous other effects downregulated the microglia markers CD68 CD80 and CD86 all of which were upregulated in untreated mutant animals 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131187 16179515 172945 14533 7872 NOS1 nNOS nNOS 15 2.2 receptor (TNFRp55) TNFRp55 and upregulated noninducible nitric oxide synthase (nNOS) nNOS and glutamine synthase (GS) GS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 131188 16179515 172947 20996 11179 SOD1 SOD1 SOD1 19 1.7 the effects of these and other candidate drugs in mutant SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 132373 16197805 174843 20996 11179 SOD1 ALS ALS 12 0.0 briefly summarize their possible roles in amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000974177821936674<>ScoreDetail__5468|IGFALS|0.000368030423848371__11179|SOD1|0.000974177821936674__ 0 0 0 0 0 126503 16326025 166566 9947 5468 IGFALS ALS ALS 12 0.3 of SSTT in therapeutic strategies against amyotrophic lateral sclerosis (ALS) ALS or early-stage Alzheimer_amp_#x2019 s disease may offer a reasonable first 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000554703949134244<>ScoreDetail__5468|IGFALS|0.000339500933627567__11179|SOD1|0.000554703949134244__ 0 0 0 0 0 126504 16326025 166567 9947 5468 IGFALS ALS ALS 10 0.3 In view of the known rapid progressive neurodegeneration associated with ALS minute variations in core body temperature may in fact demonstrate 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000554703949134244<>ScoreDetail__5468|IGFALS|0.000339500933627567__11179|SOD1|0.000554703949134244__ 0 0 0 0 0 128653 16380619 169457 20996 11179 SOD1 ALS ALS 10 0.5 of interleukin (IL)-6 IL -6 were described in patients with ALS related to an inflammatory process 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128654 16380619 169458 10463 6018 IL6 IL-6 IL-6 3 1.3 The authors compared IL-6 and tumor necrosis factor alpha TNF-alpha levels in CSF and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128655 16380619 169458 22551 11892 TNF TNF-alpha TNF-alpha 9 1.7 The authors compared IL-6 and tumor necrosis factor alpha TNF-alpha levels in CSF and sera from 10 hypoxemics and 10 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128656 16380619 169458 20996 11179 SOD1 ALS ALS 24 0.5 and sera from 10 hypoxemics and 10 normoxemics patients with ALS to those of 10 hypoxemics and 10 normoxemics neurologic controls 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128657 16380619 169458 11629 6493 LAMC2 CSF CSF 13 0.0 compared IL-6 and tumor necrosis factor alpha TNF-alpha levels in CSF and sera from 10 hypoxemics and 10 normoxemics patients with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128658 16380619 169459 20996 11179 SOD1 ALS ALS 7 0.5 The same pattern exists in patients with ALS and controls the highest levels are found in hypoxic conditions 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128659 16380619 169460 10463 6018 IL6 IL-6 IL-6 1 1.3 Elevated IL-6 levels in ALS could correspond to a normal response to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128660 16380619 169460 20996 11179 SOD1 ALS ALS 4 0.5 Elevated IL-6 levels in ALS could correspond to a normal response to hypoxemia 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128661 16380619 169461 20996 11179 SOD1 ALS ALS 13 0.5 microglia was demonstrated in the spinal cord of patients with ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128662 16380619 169463 22551 11892 TNF TNF-alpha TNF-alpha 8 1.7 An excessive production of tumor necrosis factor alpha TNF-alpha with lower CSF levels of interleukin (IL)-6 IL -6 was 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128663 16380619 169463 20996 11179 SOD1 SOD SOD 21 0.5 levels of interleukin (IL)-6 IL -6 was demonstrated in a SOD 1 mouse model suggesting an increase cytotoxic potential of microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128664 16380619 169463 11629 6493 LAMC2 CSF CSF 12 0.0 excessive production of tumor necrosis factor alpha TNF-alpha with lower CSF levels of interleukin (IL)-6 IL -6 was demonstrated in a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128665 16380619 169465 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha could act as a principal driver for neuroinflammation because its 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128666 16380619 169465 10463 6018 IL6 IL-6 IL-6 27 1.3 phases of the disease while several costimulating cytokines (IL-1_amp_#223;, IL-1_amp_#223 IL-6 and chemokines act to potentiate its effects 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128667 16380619 169466 10463 6018 IL6 IL-6 IL-6 9 1.3 However there were conflicting results either no difference in IL-6 TNF-alpha or IL-12 was found in patients with ALS and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128668 16380619 169466 22551 11892 TNF TNF-alpha TNF-alpha 10 1.7 However there were conflicting results either no difference in IL-6 TNF-alpha or IL-12 was found in patients with ALS and healthy 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128669 16380619 169466 20996 11179 SOD1 ALS ALS 19 0.5 in IL-6 TNF-alpha or IL-12 was found in patients with ALS and healthy and inflammatory controls or elevated levels of IL-6 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128670 16380619 169466 10463 6018 IL6 IL-6 IL-6 29 1.3 ALS and healthy and inflammatory controls or elevated levels of IL-6 and IL-1_amp_#223 in the CSF spinal cords and sera of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128671 16380619 169466 20996 11179 SOD1 ALS ALS 42 0.5 in the CSF spinal cords and sera of patients with ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128672 16380619 169466 11629 6493 LAMC2 CSF CSF 34 0.0 controls or elevated levels of IL-6 and IL-1_amp_#223 in the CSF spinal cords and sera of patients with ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128673 16380619 169468 10463 6018 IL6 IL-6 IL-6 1 1.3 Increased IL-6 levels were shown in pulmonary conditions such as obstructive sleep 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128674 16380619 169469 22551 11892 TNF TNF-alpha TNF-alpha 19 1.7 role of hypoxemia in the regulation of cytokines by studying TNF-alpha and IL-6 in the sera and CSF of hypoxemic and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128675 16380619 169469 10463 6018 IL6 IL-6 IL-6 22 1.3 hypoxemia in the regulation of cytokines by studying TNF-alpha and IL-6 in the sera and CSF of hypoxemic and normoxemic patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128676 16380619 169469 20996 11179 SOD1 ALS ALS 34 0.5 the sera and CSF of hypoxemic and normoxemic patients with ALS and neurologic controls 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128677 16380619 169469 11629 6493 LAMC2 CSF CSF 27 0.0 cytokines by studying TNF-alpha and IL-6 in the sera and CSF of hypoxemic and normoxemic patients with ALS and neurologic controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128678 16380619 169470 20996 11179 SOD1 ALS ALS 6 0.5 Plasma and CSF from patients with ALS and control subjects were obtained with informed consent as part 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128679 16380619 169470 11629 6493 LAMC2 CSF CSF 2 0.0 Plasma and CSF from patients with ALS and control subjects were obtained with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128680 16380619 169475 11629 6493 LAMC2 CSF CSF 2 0.0 Sera and CSF samples were stored in a refrigerator at -80degreeC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128681 16380619 169476 10463 6018 IL6 IL-6 IL-6 0 1.3 IL-6 and TNF-alpha levels in CSF and sera were determined using 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128682 16380619 169476 22551 11892 TNF TNF-alpha TNF-alpha 2 1.7 IL-6 and TNF-alpha levels in CSF and sera were determined using a chemiluminescent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128683 16380619 169476 11629 6493 LAMC2 CSF CSF 6 0.0 IL-6 and TNF-alpha levels in CSF and sera were determined using a chemiluminescent assay (QuantiGlo, QuantiGlo 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128684 16380619 169477 10463 6018 IL6 IL-6 IL-6 5 1.3 We found higher levels of IL-6 in CSF ( z = -2.7 p = 0.02 in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128685 16380619 169477 22551 11892 TNF TNF-alpha TNF-alpha 25 1.7 in serum ( z = -2.1 p = 0.04 and TNF-alpha in serum ( z = -2.5 p = 0.01 in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128686 16380619 169477 20996 11179 SOD1 ALS ALS 42 0.5 -2.5 p = 0.01 in hypoxemic vs normoxemic patients with ALS ( figure 1 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128687 16380619 169477 11629 6493 LAMC2 CSF CSF 7 0.1 We found higher levels of IL-6 in CSF ( z = -2.7 p = 0.02 in serum ( 6 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 128688 16380619 169478 10463 6018 IL6 IL-6 IL-6 10 1.3 A correlation exists between Pao 2 and levels of CSF IL-6 ( p = 0.0001 r = -0.7 serum IL-6 ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128689 16380619 169478 10463 6018 IL6 IL-6 IL-6 19 1.3 CSF IL-6 ( p = 0.0001 r = -0.7 serum IL-6 ( p = 0.007 r = -0.6 serum TNF-alpha ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128690 16380619 169478 22551 11892 TNF TNF-alpha TNF-alpha 28 1.7 serum IL-6 ( p = 0.007 r = -0.6 serum TNF-alpha ( p = 0.001 r = -0.7 in patients with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128691 16380619 169478 20996 11179 SOD1 ALS ALS 40 0.5 ( p = 0.001 r = -0.7 in patients with ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128692 16380619 169478 16035 20837 PAOX PAO Pao 4 0.0 A correlation exists between Pao 2 and levels of CSF IL-6 ( p = 0.0001 2 JUMiner_v2.2 1 0 0 2 15862 TotalCon:2<>20837|PAOX|196743|Complete__15862|SMOX|54498|Complete__<>AvaiableGeneRif=2<>BEST:15862|SMOX|0.000474608448030375<>ScoreDetail__20837|PAOX|0.000447227191413238__15862|SMOX|0.000474608448030375__ 0 0 0 0 0 128693 16380619 169478 11629 6493 LAMC2 CSF CSF 9 0.2 A correlation exists between Pao 2 and levels of CSF IL-6 ( p = 0.0001 r = -0.7 serum IL-6 5 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 128694 16380619 169479 10463 6018 IL6 IL-6 IL-6 8 1.3 In neurologic controls we found higher levels of IL-6 in CSF ( z = -2.8 p = 0.02 in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128695 16380619 169479 22551 11892 TNF TNF-alpha TNF-alpha 28 1.7 in serum ( z = -2.3 p = 0.02 and TNF-alpha in serum ( z = -2.0 p = 0.05 in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128696 16380619 169479 11629 6493 LAMC2 CSF CSF 10 0.1 In neurologic controls we found higher levels of IL-6 in CSF ( z = -2.8 p = 0.02 in serum ( 6 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 128697 16380619 169480 10463 6018 IL6 IL-6 IL-6 8 1.3 There were correlations between Pao 2 and CSF IL-6 ( p = 0.01 r = 0.5 serum IL-6 ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128698 16380619 169480 10463 6018 IL6 IL-6 IL-6 17 1.3 CSF IL-6 ( p = 0.01 r = 0.5 serum IL-6 ( p = 0.01 r = 0.5 and serum TNF-alpha 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128699 16380619 169480 22551 11892 TNF TNF-alpha TNF-alpha 27 1.7 IL-6 ( p = 0.01 r = 0.5 and serum TNF-alpha levels ( p = 0.01 r = 0.5 in neurologic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128700 16380619 169480 16035 20837 PAOX PAO Pao 4 0.0 There were correlations between Pao 2 and CSF IL-6 ( p = 0.01 r = 2 JUMiner_v2.2 1 0 0 2 15862 TotalCon:2<>20837|PAOX|196743|Complete__15862|SMOX|54498|Complete__<>AvaiableGeneRif=2<>BEST:15862|SMOX|0.000474608448030375<>ScoreDetail__20837|PAOX|0.000447227191413238__15862|SMOX|0.000474608448030375__ 0 0 0 0 0 128701 16380619 169480 11629 6493 LAMC2 CSF CSF 7 0.2 There were correlations between Pao 2 and CSF IL-6 ( p = 0.01 r = 0.5 serum IL-6 5 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 128702 16380619 169481 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha was undetectable in CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128703 16380619 169481 11629 6493 LAMC2 CSF CSF 5 0.0 TNF-alpha was undetectable in CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128704 16380619 169482 10463 6018 IL6 IL-6 IL-6 5 1.3 We found no correlation between IL-6 or TNF-alpha levels in plasma and those in CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128705 16380619 169482 22551 11892 TNF TNF-alpha TNF-alpha 7 1.7 We found no correlation between IL-6 or TNF-alpha levels in plasma and those in CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128706 16380619 169482 11629 6493 LAMC2 CSF CSF 15 0.0 between IL-6 or TNF-alpha levels in plasma and those in CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128707 16380619 169483 10463 6018 IL6 IL-6 IL-6 0 1.3 IL-6 and TNF-alpha levels did not correlate with age clinical presentation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128708 16380619 169483 22551 11892 TNF TNF-alpha TNF-alpha 2 1.7 IL-6 and TNF-alpha levels did not correlate with age clinical presentation or disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128709 16380619 169484 10463 6018 IL6 IL-6 IL-6 5 1.3 We found an increase in IL-6 levels in CSF and sera and TNF-alpha in sera in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128710 16380619 169484 22551 11892 TNF TNF-alpha TNF-alpha 12 1.7 an increase in IL-6 levels in CSF and sera and TNF-alpha in sera in hypoxemic patients with ALS and hypoxemic neurologic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128711 16380619 169484 20996 11179 SOD1 ALS ALS 20 0.5 and sera and TNF-alpha in sera in hypoxemic patients with ALS and hypoxemic neurologic controls vs normoxemic ones but no difference 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128712 16380619 169484 20996 11179 SOD1 ALS ALS 34 0.5 controls vs normoxemic ones but no difference between patients with ALS and controls 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128713 16380619 169484 11629 6493 LAMC2 CSF CSF 8 0.0 We found an increase in IL-6 levels in CSF and sera and TNF-alpha in sera in hypoxemic patients with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128714 16380619 169485 10463 6018 IL6 IL-6 IL-6 4 1.3 A correlation existed between IL-6 levels and the severity of hypoxemia in both groups suggesting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128715 16380619 169487 23910 12680 VEGFA VEGF VEGF 18 3.3 and growth factors such as vascular endothelial growth factor (VEGF) VEGF thought to play a role in the pathophysiology of sporadic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128716 16380619 169487 20996 11179 SOD1 ALS ALS 29 0.5 thought to play a role in the pathophysiology of sporadic ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128717 16380619 169488 23910 12680 VEGFA VEGF VEGF 3 3.3 Expression of the VEGF gene is mainly stimulated by hypoxia through the binding of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128718 16380619 169489 23910 12680 VEGFA VEGF VEGF 2 3.3 In CNS VEGF is mostly synthesized by endothelial cells and microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128719 16380619 169490 22551 11892 TNF TNF-alpha TNF-alpha 11 1.7 the other hand hypoxia stimulates the proinflammatory cytokines such as TNF-alpha and IL-6 mediated by others transcriptional factors nuclear factor-kappaB AP-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128720 16380619 169490 10463 6018 IL6 IL-6 IL-6 14 1.3 hand hypoxia stimulates the proinflammatory cytokines such as TNF-alpha and IL-6 mediated by others transcriptional factors nuclear factor-kappaB AP-1 and SP-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128721 16380619 169490 7683 3796 FOS AP-1 AP-1 23 1.0 TNF-alpha and IL-6 mediated by others transcriptional factors nuclear factor-kappaB AP-1 and SP-1 1 JUMiner_v2.2 1 0 0 2 3796 TotalCon:5<>3796|FOS|2353|Complete__3797|FOSB|2354|Complete__6204|JUN|3725|Complete__6205|JUNB|3726|Complete__6206|JUND|3727|Complete__<>AvaiableGeneRif=5<>BEST:3796|FOS|0.000465832105486134<>ScoreDetail__3796|FOS|0.000465832105486134__3797|FOSB|0.000334061016633131__6205|JUNB|0.000396472798029446__6204|JUN|0.000449801448317443__6206|JUND|0.000272696084612024__ 0 0 0 0 0 128722 16380619 169490 21038 11205 SP1 SP1 SP-1 25 0.1 IL-6 mediated by others transcriptional factors nuclear factor-kappaB AP-1 and SP-1 6 JUMiner_v2.2 1 0 0 2 11205 TotalCon:3<>11205|SP1|6667|Complete__26780|DAND5|199699|No_GeneRif__9514|PSG1|5669|Complete__<>AvaiableGeneRif=2<>BEST:11205|SP1|0.000455315903695708<>ScoreDetail__9514|PSG1|0.000231870616196163__11205|SP1|0.000455315903695708__ 0 0 0 0 0 128723 16380619 169491 10463 6018 IL6 IL-6 IL-6 32 1.3 excitatory amino acid nitric oxide and proinflammatory cytokines such as IL-6 TNF-alpha and IL-1_amp_#223 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128724 16380619 169491 22551 11892 TNF TNF-alpha TNF-alpha 33 1.7 amino acid nitric oxide and proinflammatory cytokines such as IL-6 TNF-alpha and IL-1_amp_#223 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128725 16380619 169492 10463 6018 IL6 IL-6 IL-6 1 1.3 Higher IL-6 and TNF-alpha levels could therefore correspond to a normal response 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128726 16380619 169492 22551 11892 TNF TNF-alpha TNF-alpha 3 1.7 Higher IL-6 and TNF-alpha levels could therefore correspond to a normal response to hypoxemia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128727 16380619 169493 10463 6018 IL6 IL-6 IL-6 7 1.3 It was demonstrated that the upregulation of IL-6 induced by hypoxemia could represent an endogenous neuroprotective mechanism against 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128728 16380619 169494 10463 6018 IL6 IL-6 IL-6 7 1.3 A neuroprotective effect of increased levels of IL-6 was also observed in animal models of ALS or in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128729 16380619 169494 20996 11179 SOD1 ALS ALS 15 0.5 levels of IL-6 was also observed in animal models of ALS or in the context of excitotoxicity after hypoxemia 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128730 16380619 169495 17610 9605 PTGS2 COX-2 COX-2 23 1.0 mediator and a major downstream product of cyclooxygenase 2 (COX-2) COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128731 16380619 169496 17610 9605 PTGS2 COX-2 COX-2 5 1.0 Increased levels of PGE-2 and COX-2 were described in patients with ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128732 16380619 169496 20996 11179 SOD1 ALS ALS 11 0.5 levels of PGE-2 and COX-2 were described in patients with ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128733 16380619 169497 17610 9605 PTGS2 COX-2 COX-2 2 1.0 PGE-2 and COX-2 presented both angiogenic properties and reciprocal interactions between COX-2/PGE-2 COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128734 16380619 169497 17610 9605 PTGS2 COX-2 COX-2 11 1.0 COX-2 presented both angiogenic properties and reciprocal interactions between COX-2/PGE-2 COX-2 PGE-2 and VEGF are described 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128735 16380619 169497 23910 12680 VEGFA VEGF VEGF 13 3.3 angiogenic properties and reciprocal interactions between COX-2/PGE-2 COX-2 PGE-2 and VEGF are described 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128736 16380619 169498 10463 6018 IL6 IL-6 IL-6 7 1.3 Our findings suggest that increased levels of IL-6 TNF-alpha PGE-2 and COX-2 observed in patients with ALS parallel 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128737 16380619 169498 22551 11892 TNF TNF-alpha TNF-alpha 8 1.7 Our findings suggest that increased levels of IL-6 TNF-alpha PGE-2 and COX-2 observed in patients with ALS parallel motor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128738 16380619 169498 17610 9605 PTGS2 COX-2 COX-2 12 1.0 findings suggest that increased levels of IL-6 TNF-alpha PGE-2 and COX-2 observed in patients with ALS parallel motor neuronal loss and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128739 16380619 169498 20996 11179 SOD1 ALS ALS 17 0.5 of IL-6 TNF-alpha PGE-2 and COX-2 observed in patients with ALS parallel motor neuronal loss and could correspond to a natural 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128740 16380619 169499 17610 9605 PTGS2 COX-2 COX-2 3 1.0 We hypothesize that COX-2 inhibitors may even be harmful in patients with ALS because 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128741 16380619 169499 20996 11179 SOD1 ALS ALS 12 0.5 that COX-2 inhibitors may even be harmful in patients with ALS because they can block the natural upregulation loop of VEGF 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128742 16380619 169499 23910 12680 VEGFA VEGF VEGF 22 3.3 ALS because they can block the natural upregulation loop of VEGF during hypoxemia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128743 16380619 169500 20996 11179 SOD1 ALS ALS 10 0.5 Rapidly progressive restrictive respiratory failure with chronic hypoxemia occurs in ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128744 16380619 169501 10463 6018 IL6 IL-6 IL-6 7 1.3 This may explain the age-associated increase in IL-6 sera levels found after exercise in patients with neuromuscular diseases 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128745 16380619 169501 20996 11179 SOD1 ALS ALS 19 0.5 levels found after exercise in patients with neuromuscular diseases including ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128746 16380619 169505 20996 11179 SOD1 ALS ALS 15 0.5 and tumor necrosis factor alpha sera levels in patients with ALS according to the condition of hypoxemia or normoxemia (Pao Pao 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00109836635384081<>ScoreDetail__5468|IGFALS|0.00109836635384081__11179|SOD1|0.000489991328667912__ 0 0 0 0 0 128747 16380619 169505 11629 6493 LAMC2 CSF CSF 0 0.0 CSF and sera interleukin-6 levels and tumor necrosis factor alpha sera 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128748 16380619 169505 16035 20837 PAOX PAO Pao 24 0.0 ALS according to the condition of hypoxemia or normoxemia (Pao Pao 2 *Significant difference (p p _lt_ 0.05 between the hypoxemic 2 JUMiner_v2.2 1 0 0 2 15862 TotalCon:2<>20837|PAOX|196743|Complete__15862|SMOX|54498|Complete__<>AvaiableGeneRif=2<>BEST:15862|SMOX|0.000474608448030375<>ScoreDetail__20837|PAOX|0.000447227191413238__15862|SMOX|0.000474608448030375__ 0 0 0 0 0 128749 16380619 169507 11629 6493 LAMC2 CSF CSF 0 0.0 CSF and sera interleukin-6 levels and tumor necrosis factor alpha sera 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 128750 16380619 169507 16035 20837 PAOX PAO Pao 23 0.0 controls according to the condition of hypoxemia or normoxemia (Pao Pao 2 *Significant difference (p p _lt_ 0.05 between the hypoxemic 2 JUMiner_v2.2 1 0 0 2 15862 TotalCon:2<>20837|PAOX|196743|Complete__15862|SMOX|54498|Complete__<>AvaiableGeneRif=2<>BEST:15862|SMOX|0.000474608448030375<>ScoreDetail__20837|PAOX|0.000447227191413238__15862|SMOX|0.000474608448030375__ 0 0 0 0 0 128751 16380619 169510 16035 20837 PAOX PAO Pao 14 0.0 to be hypoxemic if their oxygen arterial blood pressure (Pao Pao 2 was below the age-dependent minimal reference value each time 2 JUMiner_v2.2 1 0 0 2 15862 TotalCon:2<>20837|PAOX|196743|Complete__15862|SMOX|54498|Complete__<>AvaiableGeneRif=2<>BEST:15862|SMOX|0.000474608448030375<>ScoreDetail__20837|PAOX|0.000447227191413238__15862|SMOX|0.000474608448030375__ 0 0 0 0 0 128752 16380619 169515 18334 10015 RIEG2 ARS ARS 12 0.3 from the Association pour la Recherche sur la SLA (ARS) ARS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>10015|RIEG2|6012|No_GeneRif__18746|SLURP1|57152|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 128753 16380619 169515 20006 10902 SLA SLA SLA 11 0.2 by grants from the Association pour la Recherche sur la SLA (ARS) ARS 5 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>10902|SLA|6503|Complete__30605|SEPSECS|51091|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 118012 16425674 153703 20996 11179 SOD1 ALS ALS 28 0.9 as a potential subcutaneous treatment for amyotrophic lateral sclerosis (ALS), ALS stroke spinal cord injury lung inflammation and mucositis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000793984273108762<>ScoreDetail__5468|IGFALS|0.000310607237148626__11179|SOD1|0.000793984273108762__ 0 0 0 0 0 118013 16425674 153704 20996 11179 SOD1 ALS ALS 11 0.9 compound is currently undergoing a phase I clinical trial for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000793984273108762<>ScoreDetail__5468|IGFALS|0.000310607237148626__11179|SOD1|0.000793984273108762__ 0 0 0 0 0 118580 16436205 154682 20996 11179 SOD1 ALS ALS 19 1.4 dismutase (G93A-SOD1) G93A-SOD1 associated with familial amyotrophic lateral sclerosis (ALS) ALS demonstrate age-dependent neuroinflammation associated with broad-spectrum cytokine eicosanoid and oxidant 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118581 16436205 154685 20996 11179 SOD1 SOD1 SOD1-expressing 9 1.4 Nonetheless astrocytes cultured from G93A-SOD1 (but but not wild-type human SOD1-expressing transgenic mouse pups demonstrated a significant elevation in either the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118582 16436205 154685 12110 6711 LTB LTB LTB 41 1.8 E 2 (PGE PGE 2 and leukotriene B 4 (LTB LTB 4 inducible nitric oxide synthase (iNOS) iNOS and _amp_#x02022 NO 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118583 16436205 154685 14535 7873 NOS2A iNOS iNOS 48 3.2 B 4 (LTB LTB 4 inducible nitric oxide synthase (iNOS) iNOS and _amp_#x02022 NO (indexed indexed by nitrite release into the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118584 16436205 154686 18741 10289 RPA1 RPA RPAs 20 0.0 G93A-SOD1 cells as assessed by multiprobe ribonuclease protection assays (RPAs) RPAs for their mRNA transcripts 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118585 16436205 154688 20996 11179 SOD1 ALS ALS 10 1.4 These findings support a role for active glial involvement in ALS and may provide a useful cell culture tool for the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118586 16436205 154690 20996 11179 SOD1 ALS ALS 10 1.4 the proximal cause of paralysis in amyotrophic lateral sclerosis (ALS) ALS is the death of motor neurons it is becoming widely 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118587 16436205 154690 20996 11179 SOD1 ALS ALS 27 1.4 it is becoming widely accepted that motor neuron death in ALS is not cell autonomous but depends upon active and passive 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118588 16436205 154691 20996 11179 SOD1 ALS ALS 4 1.4 The neuron-cell autonomy of ALS pathogenesis has been strongly questioned by a number of studies 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118589 16436205 154692 20996 11179 SOD1 SOD1 SOD1 17 1.7 al created a strain of transgenic mice that express mutant SOD1 specifically in neurons 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118590 16436205 154695 20996 11179 SOD1 SOD1 SOD1 4 1.7 Selective expression of mutant SOD1 only in astroglia causes a type of astrogliosis but fails 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118591 16436205 154695 20996 11179 SOD1 SOD1 SOD1 29 1.7 motor neuron disease 3 in the absence of simultaneous mutant SOD1 expression in neurons 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118592 16436205 154696 20996 11179 SOD1 SOD1 SOD1 14 1.7 recently showed that the rate of disease progression in mutant SOD1 chimeric mice depends on the extraneuronal expression of mutant SOD1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118593 16436205 154696 20996 11179 SOD1 SOD1 SOD1 24 1.7 SOD1 chimeric mice depends on the extraneuronal expression of mutant SOD1 4 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118594 16436205 154697 20996 11179 SOD1 SOD1 SOD1 9 1.7 The survival of chimeric mice was dependent upon mutant SOD1 expression in neurons but also highly dependent on the number 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118595 16436205 154697 20996 11179 SOD1 SOD1 SOD1-expressing 23 1.4 but also highly dependent on the number of ambient mutant SOD1-expressing non-neuronal cells 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118596 16436205 154698 20996 11179 SOD1 ALS ALS 10 1.4 These studies provide strong incentive to consider glial involvement in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118597 16436205 154700 20996 11179 SOD1 ALS ALS 7 1.4 Using the G93A-SOD1 mutant mouse model for ALS Gurney et al reported dramatically increased numbers of MHC-II microglia 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118598 16436205 154702 20996 11179 SOD1 ALS ALS-linked 38 1.4 the application of this cytokine in cell culture studies of ALS-linked glial activation 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118599 16436205 154705 20996 11179 SOD1 ALS ALS 23 1.4 antagonist nordihydroguaiaretic acid (NDGA) NDGA slows disease progression in the ALS mouse 14 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118600 16436205 154706 20996 11179 SOD1 ALS ALS 16 1.4 neuroinflammatory response antagonism of which may slow the progression of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118601 16436205 154707 20996 11179 SOD1 ALS ALS 13 1.4 better understand the contributions of astroglia to neuroinflammation in the ALS context and to create a tool for the study of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118602 16436205 154712 20996 11179 SOD1 SOD1 SOD1 8 1.7 Expression of high copy numbers of wild-type human SOD1 had no effect or slightly diminished the inflammatory indices 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118603 16436205 154713 20996 11179 SOD1 SOD1 SOD1 4 1.7 These findings suggest that SOD1 mutations fundamentally alter the phenotype of astrocytes placing the cells 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118604 16436205 154715 20996 11179 SOD1 SOD1 SOD1 23 1.7 Jackson Laboratories (Bar Bar Harbor ME strain designation B6SJL-Tg(SOD1 B6SJL-Tg SOD1 G93A)1Gur/J; G93A 1Gur J 15 -17 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118605 16436205 154716 20996 11179 SOD1 SOD1 SOD1 15 1.7 were used that express equivalent protein levels of wild-type human SOD1 (B6SJL-TgN-(SOD1 B6SJL-TgN- SOD1 G93A -2Gur Jackson Laboratories 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118606 16436205 154716 20996 11179 SOD1 SOD1 SOD1 16 1.7 express equivalent protein levels of wild-type human SOD1 (B6SJL-TgN-(SOD1 B6SJL-TgN- SOD1 G93A -2Gur Jackson Laboratories 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118607 16436205 154719 20996 11179 SOD1 SOD1 SOD1 29 1.7 methods 18 from G93A-SOD1 mice matched nontransgenic littermates or wildtype-human SOD1 expressing mice 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118608 16436205 154723 6895 3530 F12 F12 F12 17 0.0 of 50% Dulbecco's Modified Essential Medium (DMEM) DMEM and 50% F12 media containing 10% heat-inactivated fetal bovine serum 1% glutamine and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118609 16436205 154733 8254 4235 GFAP GFAP GFAP 25 2.5 to identify microglia and rhodamine-conjugated rabbit anti-glial fibrillary protein (GFAP) GFAP antibody (Chemicon) Chemicon to identify astroctyes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118610 16436205 154742 18741 10289 RPA1 RPA RPAs 10 0.0 and methods Ribonuclease protection assays Multiprobe ribonuclease protection assays (RPAs) RPAs were performed as described 14 7 8 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118611 16436205 154745 18741 10289 RPA1 RPA RPA 7 0.0 Panels of mRNA were detected using commercial RPA kits (Riboquant_amp_#x02122;, Riboquant_amp_#x02122 Pharmingen San Diego CA 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118612 16436205 154751 8118 4141 GAPDH GAPDH GAPDH 19 0.0 mRNA band was normalized to the sum of the L32 GAPDH bands 1 JUMiner_v2.2 1 1 gapdh; 0 0 0 0 0 0 0 0 118613 16436205 154752 12110 6711 LTB LTB LTB 8 1.8 Materials and methods Eicosanoid assays PGE 2 and LTB 4 were measured in cell culture medium using commercially available 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118614 16436205 154763 12519 6983 ME1 MES MES 7 0.0 were lysed in 20 mM 2-(N-morpholino)-ethanesulfonate 2- N-morpholino -ethanesulfonate (MES) MES buffer pH 5.5 containing 0.1% triton X-100 5 mM biotin-LC-hydrazide 1 JUMiner_v2.2 1 0 0 2 7121 TotalCon:2<>6983|ME1|4199|Complete__7121|MKS1|54903|Complete__<>AvaiableGeneRif=2<>BEST:7121|MKS1|0.000281213582841022<>ScoreDetail__7121|MKS1|0.000281213582841022__6983|ME1|0.000245218244237371__ 0 0 0 0 0 118615 16436205 154770 18741 10289 RPA1 RPA RPAs 66 0.0 immunoblot (not not shown or cytokine expression patterns assessed by RPAs (data data not shown 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118616 16436205 154772 8254 4235 GFAP GFAP GFAP 21 2.5 based on immunocytochemical staining with anti-glial fibrillary acidic protein (GFAP) GFAP (not not illustrated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118617 16436205 154778 18741 10289 RPA1 RPA RPA 10 0.0 Results Specific cytokine expressioin differences occur in G93A-SOD1 astrocytes Multiprobe RPA methods were used to assess genotype-dependent differences in cytokine-stimulated cytokine 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118618 16436205 154781 8118 4141 GAPDH GAPDH GAPDH 11 0.0 G93A-SOD1 cells demonstrated lower levels of housekeeping messages L32 and GAPDH than did non-transgenic matched cell cultures (Fig Fig 1 1 JUMiner_v2.2 1 1 gapdh; 0 0 0 0 0 0 0 0 118619 16436205 154782 8118 4141 GAPDH GAPDH GAPDH 22 0.0 of non-housekeeping genes such that the ratio of L32 and GAPDH to total mRNA is fundamentally skewed in G93A-SOD1 gial cultures 1 JUMiner_v2.2 1 1 gapdh; 0 0 0 0 0 0 0 0 118620 16436205 154786 8118 4141 GAPDH GAPDH GAPDH 32 0.0 (% % change in TNF_amp_#x003b1 bands without normalization to L32 GAPDH = 1132 _amp_#x000b1 618% in G93A-SOD1 cells vs 242 _amp_#x000b1 1 JUMiner_v2.2 1 1 gapdh; 0 0 0 0 0 0 0 0 118621 16436205 154787 22585 11925 TNFSF10 TRAIL TRAIL 0 2.2 TRAIL (TNF-Related TNF-Related Apoptosis-Inducing Ligand was likewise very markedly upregulated in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118622 16436205 154787 22551 11892 TNF TNF TNF-Related 1 1.2 TRAIL (TNF-Related TNF-Related Apoptosis-Inducing Ligand was likewise very markedly upregulated in G93A-SOD1 cells 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118623 16436205 154790 10463 6018 IL6 IL-6 IL-6 0 1.8 IL-6 which has some neuroprotective functions 20 tended to decrease in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118624 16436205 154792 20996 11179 SOD1 SOD1 SOD1 27 1.7 or from mice expressing high copy numbers of wildtype human SOD1 (wt-hSOD1) wt-hSOD1 were stimulated with IFN_amp_#x003b3 TNF_amp_#x003b1 or both for 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118625 16436205 154792 12110 6711 LTB LTB LTB 46 1.8 for 24 hours and medium was assayed by ELISA for LTB 4 and PGE 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118626 16436205 154797 12110 6711 LTB LTB LTB 7 1.8 A somewhat different pattern was observed for LTB 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118627 16436205 154799 12110 6711 LTB LTB LTB 1 1.8 However LTB 4 was synergistically inducible by IFN_amp_#x003b3 TNF_amp_#x003b1 in both genotypes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118628 16436205 154800 12110 6711 LTB LTB LTB 4 1.8 The relative increase in LTB 4 during cytokine stimulation was similar between the genotypes but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118629 16436205 154800 12110 6711 LTB LTB LTB 15 1.8 4 during cytokine stimulation was similar between the genotypes but LTB 4 remained at least 2-fold elevated in G93A-SOD1 cultures relative 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118630 16436205 154801 20996 11179 SOD1 SOD1 SOD1 18 1.7 glial arachidonic acid metabolism as a function of the mutant SOD1 transgene 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118631 16436205 154803 14535 7873 NOS2A iNOS iNOS 1 3.2 Results iNOS expression and nitric oxide synthesis is increased in G93A-SOD1 glia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118632 16436205 154808 14535 7873 NOS2A iNOS iNOS 3 3.2 Elevated levels of iNOS protein could be detected in G93A-SOD1 astrocytes relative to nontransgenic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118633 16436205 154820 20996 11179 SOD1 SOD1 SOD1 8 1.7 Curiously no major protein carbonylation band assignable to SOD1 was found in any G93A-SOD1 astrocyte lysates whereas a major 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118634 16436205 154820 20996 11179 SOD1 SOD1 SOD1 23 1.7 G93A-SOD1 astrocyte lysates whereas a major carbonylated protein identifiable as SOD1 was previously demonstrated in spinal cord extracts from symptomatic G93A-SOD1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118635 16436205 154826 20996 11179 SOD1 ALS ALS 4 1.4 In murine models of ALS neuroinflammation is robust as indicated by broad-spectrum cytokine upregulation plus 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118636 16436205 154829 20996 11179 SOD1 SOD1 SOD1 18 1.7 relevant pathways that are perturbed by the insertion of mutant SOD1 transgenes and has slowed the development of new therapeutic modalities 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118637 16436205 154830 20996 11179 SOD1 SOD1 SOD1 26 1.7 studies of signal transduction pathways that are sensitive to mutant SOD1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118638 16436205 154831 20996 11179 SOD1 SOD1 SOD1 17 1.7 recent reports of cytokine hyper-expression in the CNS of mutant SOD1 mice preceding motor neuron death 6 -8 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118639 16436205 154833 14535 7873 NOS2A iNOS iNOS 23 3.2 of TNF_amp_#x003b1 COX-II and to a lesser extent 5LOX and iNOS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118640 16436205 154836 20996 11179 SOD1 SOD1 SOD1 5 1.7 Thus glial over-expression of mutant SOD1 (but but not wild-type SOD1 elicits a fundamental influence upon 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118641 16436205 154836 20996 11179 SOD1 SOD1 SOD1 9 1.7 Thus glial over-expression of mutant SOD1 (but but not wild-type SOD1 elicits a fundamental influence upon multiple gene regulatory pathways 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118642 16436205 154837 20996 11179 SOD1 ALS ALS 9 1.4 One of the most important unaccomplished necessities in understanding ALS is to elucidate the toxic gain-of-function(s) gain-of-function s inherent to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00115672406106539<>ScoreDetail__5468|IGFALS|0.000514378092392103__11179|SOD1|0.00115672406106539__ 0 0 0 0 0 118643 16436205 154837 20996 11179 SOD1 SOD1 SOD1 18 1.7 is to elucidate the toxic gain-of-function(s) gain-of-function s inherent to SOD1 mutants 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118644 16436205 154840 20996 11179 SOD1 SOD1 SOD1 10 1.7 One likely mode of action is through accumulation of mutant SOD1 within the mitochondrial intermembrane space 21 22 which may facilitate 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118645 16436205 154842 20996 11179 SOD1 SOD1 SOD1 21 1.7 be released from glial mitochondria secondary to accumulation of mutant SOD1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118646 16436205 154846 10463 6018 IL6 IL6 IL6 5 1.8 Most cytokines including TNF_amp_#x003b1 and IL6 that we find upregulated in primary glial cultures or in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118647 16436205 154853 12110 6711 LTB LTB LTB 10 1.8 Figure 2 Comparison of basal and cytokine-stimulated PGE 2 and LTB 4 production by nontransgenic primary mouse astrocytes G93A-SOD1 mouse astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118648 16436205 154853 20996 11179 SOD1 SOD1 SOD1-expressing 25 1.4 primary mouse astrocytes G93A-SOD1 mouse astrocytes or wild type human SOD1-expressing mouse astrocytes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118649 16436205 154854 604 435 ALOX5 5-LOX 5-LOX 9 2.3 Insets show western blot analysis of basal COX-II and 5-LOX (more more ... 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118650 16436205 154855 14535 7873 NOS2A iNOS iNOS 2 3.2 Figure 3 iNOS protein expression and NO 2 -formation in cultured nontransgenic or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 118891 16445350 155372 926 620 APP amyloid amyloid 17 1.0 discusses differences in critical pathways of immune/inflammation immune inflammation and amyloid formation between Parkinson's disease and amyotrophic lateral sclerosis as well 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 122173 16510725 160989 20996 11179 SOD1 ALS ALS 20 1.4 pathogenesis of motor neuron death in amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122174 16510725 160990 22551 11892 TNF TNF-alpha TNF-alpha 12 1.7 mediators of inflammation such as the cytokine tumor necrosis factor-alpha TNF-alpha and its superfamily member fibroblast-associated cell-surface ligand (FasL) FasL have 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122175 16510725 160990 7334 11936 FASLG FasL FasL 21 3.2 factor-alpha TNF-alpha and its superfamily member fibroblast-associated cell-surface ligand (FasL) FasL have been implicated in apoptosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122176 16510725 160991 22551 11892 TNF TNF-alpha TNF-alpha 3 1.7 We found increased TNF-alpha and FasL immunoreactivity in lumbar spinal cord sections of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122177 16510725 160991 7334 11936 FASLG FasL FasL 6 3.2 We found increased TNF-alpha and FasL immunoreactivity in lumbar spinal cord sections of ALS patients and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122178 16510725 160991 20996 11179 SOD1 ALS ALS 14 1.4 TNF-alpha and FasL immunoreactivity in lumbar spinal cord sections of ALS patients and G93A transgenic mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122179 16510725 160992 22551 11892 TNF TNF-alpha TNF-alpha 2 1.7 Both increased TNF-alpha and FasL immunostaining in the lumbar spinal cord of the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122180 16510725 160992 7334 11936 FASLG FasL FasL 5 3.2 Both increased TNF-alpha and FasL immunostaining in the lumbar spinal cord of the G93A SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122181 16510725 160992 20996 11179 SOD1 SOD1 SOD1 15 1.9 FasL immunostaining in the lumbar spinal cord of the G93A SOD1 transgenic mice occurred at 40-60 d well before the onset 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122182 16510725 160993 22551 11892 TNF TNF-alpha TNF-alpha 18 1.7 its analog lenalidomide pharmacological agents that inhibit the expression of TNF-alpha and other cytokines by destabilizing their mRNA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122183 16510725 160995 22551 11892 TNF TNF-alpha TNF-alpha 7 1.7 Treated G93A mice showed a reduction in TNF-alpha and FasL immunoreactivity as well as their mRNA in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122184 16510725 160995 7334 11936 FASLG FasL FasL 10 3.2 Treated G93A mice showed a reduction in TNF-alpha and FasL immunoreactivity as well as their mRNA in the lumbar spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122185 16510725 160996 10437 5992 IL1B IL-1 IL-1 6 1.3 Both compounds also reduced interleukin (IL)-12p40, IL -12p40 IL-1 alpha and IL-1 beta and increased IL-RA and TGF-beta1 mRNA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122186 16510725 160996 10437 5992 IL1B IL-1 IL-1 9 1.3 compounds also reduced interleukin (IL)-12p40, IL -12p40 IL-1 alpha and IL-1 beta and increased IL-RA and TGF-beta1 mRNA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122187 16510725 160996 10469 6024 IL7R ILRA IL-RA 13 0.3 (IL)-12p40, IL -12p40 IL-1 alpha and IL-1 beta and increased IL-RA and TGF-beta1 mRNA 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122188 16510725 160996 22059 11766 TGFB1 TGFB1 TGF-beta1 15 0.1 -12p40 IL-1 alpha and IL-1 beta and increased IL-RA and TGF-beta1 mRNA 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122189 16510725 160997 20996 11179 SOD1 ALS ALS 14 1.4 lenalidomide bear promise as therapeutic interventions for the treatment of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122190 16510725 160998 20996 11179 SOD1 SOD1 SOD1 3 1.9 Key words G93A SOD1 thalidomide lenalidomide TNF-alpha FasL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122191 16510725 160998 22551 11892 TNF TNF-alpha TNF-alpha 6 1.7 Key words G93A SOD1 thalidomide lenalidomide TNF-alpha FasL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122192 16510725 160998 7334 11936 FASLG FasL FasL 8 3.2 Key words G93A SOD1 thalidomide lenalidomide TNF-alpha FasL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122193 16510725 160999 20996 11179 SOD1 ALS ALS 3 1.4 Amyotrophic lateral sclerosis (ALS) ALS is a fatal disease characterized by an age-related progressive degeneration 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122194 16510725 160999 19891 29546 SH3YL1 Ray Ray-Chaudhuri 23 0.6 of both upper and lower motor neurons (Leigh Leigh and Ray-Chaudhuri 1994 11 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 122195 16510725 161000 20996 11179 SOD1 ALS ALS 3 1.4 Approximately 5-10% of ALS cases are familial and exhibit an autosomal-dominant pattern of inheritance 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122196 16510725 161001 20996 11179 SOD1 ALS ALS 7 1.4 A major discovery in the study of ALS was the finding of missense mutations in the enzyme copper-zinc 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122197 16510725 161001 20996 11179 SOD1 SOD1 SOD1 20 1.9 of missense mutations in the enzyme copper-zinc superoxide dismutase (SOD1), SOD1 which is associated with 15-20% of familial ALS cases (Rosen 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122198 16510725 161001 20996 11179 SOD1 ALS ALS 28 1.4 dismutase (SOD1), SOD1 which is associated with 15-20% of familial ALS cases (Rosen Rosen et al. 1993 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122199 16510725 161003 20996 11179 SOD1 ALS ALS 8 1.4 Neuroinflammation is one of the pathological hallmarks in ALS transgenic mice (West West et al. 1991 Almer et al. 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122200 16510725 161004 22551 11892 TNF TNF-alpha TNF-alpha 4 1.7 Tumor necrosis factor-alpha TNF-alpha is a major inflammatory cytokine that elicits a wide range 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122201 16510725 161004 22561 11916 TNFRSF1A TNFR1 TNF-R1 37 2.2 mediates its biological effects through activation of two distinct receptors TNF-R1 and TNF-R2 (Tartaglia Tartaglia and Goeddel 1992 alpha and its 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122202 16510725 161004 22562 11917 TNFRSF1B TNFR2 TNF-R2 39 1.2 biological effects through activation of two distinct receptors TNF-R1 and TNF-R2 (Tartaglia Tartaglia and Goeddel 1992 alpha and its proapoptotic receptor 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122203 16510725 161004 22561 11916 TNFRSF1A TNFR1 TNF-R1 49 2.2 (Tartaglia Tartaglia and Goeddel 1992 alpha and its proapoptotic receptor TNF-R1 mRNA are elevated at late presymptomatic stages of disease in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122204 16510725 161004 22551 11892 TNF TNF TNF 98 1.7 G93A mice (Hensley Hensley et al. 2002 alpha and soluble TNF receptor are elevated in serum of humans with ALS (Poloni 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122205 16510725 161004 20996 11179 SOD1 ALS ALS 107 1.4 soluble TNF receptor are elevated in serum of humans with ALS (Poloni Poloni et al. 2000 alpha is capable of activating 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122206 16510725 161005 7334 11936 FASLG FasL FasL 3 3.2 Fibroblast-associated cell-surface ligand (FasL) FasL may play a critical role in the death of motor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122207 16510725 161005 20996 11179 SOD1 SOD1 SOD1 18 1.9 role in the death of motor neurons associated with mutant SOD1 (Raoul Raoul et al. 2002 alpha can induce FasL (Pinkoski 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122208 16510725 161005 7334 11936 FASLG FasL FasL 26 3.2 mutant SOD1 (Raoul Raoul et al. 2002 alpha can induce FasL (Pinkoski Pinkoski et al. 2002 alpha binds to its receptor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122209 16510725 161005 22561 11916 TNFRSF1A TNFR1 TNF-R1 37 2.2 et al. 2002 alpha binds to its receptor (e.g., e.g. TNF-R1 similar to the events that take place when FasL binds 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122210 16510725 161005 7334 11936 FASLG FasL FasL 46 3.2 e.g. TNF-R1 similar to the events that take place when FasL binds to Fas then death-inducing signaling complex (DISC) DISC will 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122211 16510725 161005 7333 11920 FAS FAS Fas 49 2.1 to the events that take place when FasL binds to Fas then death-inducing signaling complex (DISC) DISC will form and caspase-8 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000487080126608893<>ScoreDetail__11920|FAS|0.000487080126608893__3594|FASN|0.000378882763346198__ 0 0 0 0 0 122212 16510725 161005 3532 1509 CASP8 caspase-8 caspase-8 58 2.0 Fas then death-inducing signaling complex (DISC) DISC will form and caspase-8 is activated which leads to apoptotic cell death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122213 16510725 161006 22551 11892 TNF TNF-alpha TNF-alpha 10 1.7 In the present study we examined the temporal pattern of TNF-alpha and FasL immunoreactivity in the lumbar spinal cord of G93A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122214 16510725 161006 7334 11936 FASLG FasL FasL 13 3.2 present study we examined the temporal pattern of TNF-alpha and FasL immunoreactivity in the lumbar spinal cord of G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122215 16510725 161007 22551 11892 TNF TNF-alpha TNF-alpha 8 1.7 Because previous work showed that the pro-inflammatroy cytokines TNF-alpha and FasL are elevated in both human and mouse models 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122216 16510725 161007 7334 11936 FASLG FasL FasL 11 3.2 Because previous work showed that the pro-inflammatroy cytokines TNF-alpha and FasL are elevated in both human and mouse models of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122217 16510725 161007 20996 11179 SOD1 ALS ALS 21 1.4 FasL are elevated in both human and mouse models of ALS and play a role in the pathogenesis of ALS we 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122218 16510725 161007 20996 11179 SOD1 ALS ALS 30 1.4 of ALS and play a role in the pathogenesis of ALS we tested the neuroprotective effects of thalidomide and lenalidomide two 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122219 16510725 161007 22551 11892 TNF TNF-alpha TNF-alpha 45 1.7 effects of thalidomide and lenalidomide two immunomodulatory agents that inhibit TNF-alpha production (Corral Corral et al. 1999 Bartlett et al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122220 16510725 161009 20996 11179 SOD1 SOD1 SOD1 1 1.9 G93A SOD1 transgenic familial ALS mice (high high copy number (Gurney Gurney 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122221 16510725 161009 20996 11179 SOD1 ALS ALS 4 1.4 G93A SOD1 transgenic familial ALS mice (high high copy number (Gurney Gurney et al. 1994 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122222 16510725 161017 20996 11179 SOD1 SOD1 SOD1 3 1.9 Six N1029 (wild-type wild-type SOD1 transgenic mice and six mice from the thalidomide- and vehicle-treated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122223 16510725 161039 22551 11892 TNF TNF-alpha TNF-alpha 6 1.7 The primers used were as follows TNF-alpha sense 5'-GACCCAGTGTGGGAAG-3' and antisense 5'-GGTTCAGTGATGT-AGCGA-3' glyceraldehyde-3-phosphate dehydrogenase (GAPDH), GAPDH sense 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122224 16510725 161039 8118 4141 GAPDH GAPDH GAPDH 15 1.6 follows TNF-alpha sense 5'-GACCCAGTGTGGGAAG-3' and antisense 5'-GGTTCAGTGATGT-AGCGA-3' glyceraldehyde-3-phosphate dehydrogenase (GAPDH), GAPDH sense 5'-CCATGGAGAAGGCTGGG-3' and antisense 5'-CAAAA-GTTGTCATGGATGACC-3' 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122225 16510725 161045 22551 11892 TNF TNF-alpha TNF-alpha 3 1.7 The amounts of TNF-alpha and GAPDH cDNA were calculated using linear regression analysis from 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122226 16510725 161045 8118 4141 GAPDH GAPDH GAPDH 6 1.6 The amounts of TNF-alpha and GAPDH cDNA were calculated using linear regression analysis from standard curves 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122227 16510725 161045 22551 11892 TNF TNF-alpha TNF-alpha 19 1.7 calculated using linear regression analysis from standard curves for both TNF-alpha and GAPDH and the amount of TNF-alpha cDNA was expressed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122228 16510725 161045 8118 4141 GAPDH GAPDH GAPDH 22 1.6 linear regression analysis from standard curves for both TNF-alpha and GAPDH and the amount of TNF-alpha cDNA was expressed as a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122229 16510725 161045 22551 11892 TNF TNF-alpha TNF-alpha 27 1.7 curves for both TNF-alpha and GAPDH and the amount of TNF-alpha cDNA was expressed as a percentage of GAPDH 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122230 16510725 161045 8118 4141 GAPDH GAPDH GAPDH 36 1.6 amount of TNF-alpha cDNA was expressed as a percentage of GAPDH 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122231 16510725 161057 22551 11892 TNF TNF-alpha TNF-alpha 7 1.7 The sections were immunostained with antibodies to TNF-alpha (Serotec, Serotec Raleigh NC FasL (Santa Santa Cruz Biotechnology Santa 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122232 16510725 161057 7334 11936 FASLG FasL FasL 12 3.2 were immunostained with antibodies to TNF-alpha (Serotec, Serotec Raleigh NC FasL (Santa Santa Cruz Biotechnology Santa Cruz CA CD40 (Serotec, Serotec 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122233 16510725 161057 3889 11919 CD40 CD40 CD40 19 0.6 Raleigh NC FasL (Santa Santa Cruz Biotechnology Santa Cruz CA CD40 (Serotec, Serotec Oxford UK and glial fibrillary acid protein (GFAP; 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122234 16510725 161057 8254 4235 GFAP GFAP GFAP 28 2.5 (Serotec, Serotec Oxford UK and glial fibrillary acid protein (GFAP; GFAP Dako Carpinteria CA using a modified avidin-biotin peroxidase technique 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122235 16510725 161061 22551 11892 TNF TNF-alpha TNF-alpha 10 1.7 Double immunofluorescence was performed to demonstrate the glial localization of TNF-alpha and FasL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122236 16510725 161061 7334 11936 FASLG FasL FasL 13 3.2 was performed to demonstrate the glial localization of TNF-alpha and FasL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122237 16510725 161065 20996 11179 SOD1 ALS ALS 5 1.4 Paraffin-embedded spinal cord tissues from ALS patients ( n = 6 four males and two females 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122238 16510725 161066 20996 11179 SOD1 ALS ALS 3 1.4 One of the ALS patients had an I113T mutation of the SOD1 gene 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122239 16510725 161066 20996 11179 SOD1 SOD1 SOD1 11 1.9 of the ALS patients had an I113T mutation of the SOD1 gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122240 16510725 161068 20996 11179 SOD1 ALS ALS 11 1.4 age at death was 59 years (range, range 27-69 for ALS patients and 65 years (range, range 54-73 for controls 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122241 16510725 161069 22551 11892 TNF TNF-alpha TNF-alpha 10 1.7 sections (7 7 microm thick were prepared and processed for TNF-alpha or FasL immunohistochemistry as described above 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122242 16510725 161069 7334 11936 FASLG FasL FasL 13 3.2 7 microm thick were prepared and processed for TNF-alpha or FasL immunohistochemistry as described above 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122243 16510725 161073 18741 10289 RPA1 RPA RPA 4 0.0 Commercial ribonuclease protection assay (RPA) RPA probe sets (PharMingen, PharMingen San Diego CA were used to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122244 16510725 161082 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha and FasL immunoreactivity in G93A SOD1 mouse model of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122245 16510725 161082 7334 11936 FASLG FasL FasL 3 3.2 TNF-alpha and FasL immunoreactivity in G93A SOD1 mouse model of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122246 16510725 161082 20996 11179 SOD1 SOD1 SOD1 7 1.9 TNF-alpha and FasL immunoreactivity in G93A SOD1 mouse model of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122247 16510725 161082 20996 11179 SOD1 ALS ALS 11 1.4 TNF-alpha and FasL immunoreactivity in G93A SOD1 mouse model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122248 16510725 161083 22551 11892 TNF TNF-alpha TNF-alpha 6 1.7 We investigated the temporal pattern of TNF-alpha and FasL immunoreactivity in G93A SOD1 mice at 40 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122249 16510725 161083 7334 11936 FASLG FasL FasL 9 3.2 We investigated the temporal pattern of TNF-alpha and FasL immunoreactivity in G93A SOD1 mice at 40 and 60 d 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122250 16510725 161083 20996 11179 SOD1 SOD1 SOD1 13 1.9 the temporal pattern of TNF-alpha and FasL immunoreactivity in G93A SOD1 mice at 40 and 60 d (asymptomatic), asymptomatic 90 d 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122251 16510725 161084 22551 11892 TNF TNF-alpha TNF-alpha 4 1.7 Immunohistochemical analysis showed little TNF-alpha immunoreactivity at 40 d which appeared similar to controls in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122252 16510725 161085 22551 11892 TNF TNF-alpha TNF-alpha 15 1.7 from G93A mice with a healthy appearance were stained with TNF-alpha moderately and immunoreactivity became more intense at 90 and 110 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122253 16510725 161087 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha colocalized with the motor neuron marker (SMI-32) SMI-32 (Kiaei Kiaei 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122254 16510725 161087 8254 4235 GFAP GFAP GFAP 32 2.5 of age as demonstrated by colocalization with the astrocyte marker GFAP by double immunofluorescence ( Fig 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122255 16510725 161088 20996 11179 SOD1 ALS ALS 5 1.4 Pro-inflammatory cytokines are implicated in ALS pathogenesis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122256 16510725 161089 20996 11179 SOD1 ALS ALS 6 1.4 Previous evidence for inflammatory mechanisms in ALS comes from a number of studies (Almer Almer et al. 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122257 16510725 161089 11629 6493 LAMC2 CSF CSF 22 0.3 (Almer Almer et al. 2001 beta are increased in the CSF and spinal cord respectively in ALS patients (Almer Almer et 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 122258 16510725 161089 20996 11179 SOD1 ALS ALS 28 1.4 are increased in the CSF and spinal cord respectively in ALS patients (Almer Almer et al. 1999 beta is also increased 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122259 16510725 161089 20996 11179 SOD1 ALS ALS 43 1.4 1999 beta is also increased in transgenic mouse models of ALS (Ghezzi Ghezzi et al. 1998 beta activation slowed disease progression 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122260 16510725 161089 20996 11179 SOD1 ALS ALS 59 1.4 activation slowed disease progression in a transgenic mouse model of ALS (Li Li et al. 2000 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122261 16510725 161090 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha and FasL are important mediators of inflammation and they play 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122262 16510725 161090 7334 11936 FASLG FasL FasL 3 3.2 TNF-alpha and FasL are important mediators of inflammation and they play a role 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122263 16510725 161091 20996 11179 SOD1 ALS ALS 6 1.4 Studies performed in mouse models of ALS and patients with ALS show increases in TNF-alpha. 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122264 16510725 161091 20996 11179 SOD1 ALS ALS 10 1.4 Studies performed in mouse models of ALS and patients with ALS show increases in TNF-alpha. 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122265 16510725 161091 22551 11892 TNF TNF TNF-alpha. 14 1.7 models of ALS and patients with ALS show increases in TNF-alpha. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122266 16510725 161092 20996 11179 SOD1 ALS ALS 1 1.4 In ALS patients antigenic TNF-alpha and its soluble receptors measured by ELISA 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122267 16510725 161092 22551 11892 TNF TNF-alpha TNF-alpha 4 1.7 In ALS patients antigenic TNF-alpha and its soluble receptors measured by ELISA were significantly higher 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122268 16510725 161092 20996 11179 SOD1 ALS ALS 17 1.4 its soluble receptors measured by ELISA were significantly higher in ALS patients than in healthy controls (Poloni Poloni et al. 2000 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122269 16510725 161092 7333 11920 FAS FAS Fas-associated 87 2.1 receptors was also present A study using RPAs showed increased Fas-associated death domain (FADD) FADD and TNF-alpha receptor p55 at 80 1 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000487080126608893<>ScoreDetail__11920|FAS|0.000487080126608893__3594|FASN|0.000378882763346198__ 0 0 0 0 0 122270 16510725 161092 6920 3573 FADD FADD FADD 90 0.9 A study using RPAs showed increased Fas-associated death domain (FADD) FADD and TNF-alpha receptor p55 at 80 d which increased further 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122271 16510725 161092 22551 11892 TNF TNF-alpha TNF-alpha 92 1.7 using RPAs showed increased Fas-associated death domain (FADD) FADD and TNF-alpha receptor p55 at 80 d which increased further at 120 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122272 16510725 161092 22561 11916 TNFRSF1A p55 p55 95 1.7 showed increased Fas-associated death domain (FADD) FADD and TNF-alpha receptor p55 at 80 d which increased further at 120 d in 1 JUMiner_v2.2 1 0 0 2 11916 TotalCon:5<>8981|PIK3R3|8503|Complete__9557|PSMD12|5718|No_GeneRif__3446|ERG|2078|Complete__11148|FSCN1|6624|Complete__11916|TNFRSF1A|7132|Complete__<>AvaiableGeneRif=4<>BEST:11916|TNFRSF1A|0.000490419368256165<>ScoreDetail__11916|TNFRSF1A|0.000490419368256165__3446|ERG|0.00037662470835322__11148|FSCN1|0.000350512692918191__8981|PIK3R3|0.000218616401088224__ 0 0 0 0 0 122273 16510725 161092 20996 11179 SOD1 SOD1 SOD1 123 1.9 alpha was increased in the lumbar spinal cord of G37R SOD1 mice at 7 and 10 months of age and the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122274 16510725 161092 10437 5992 IL1B IL-1 IL-1 141 1.3 age and the signal was unchanged in the absence of IL-1 beta (Nguyen Nguyen et al. 2001 alpha expression at 11 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122275 16510725 161092 20996 11179 SOD1 SOD1 SOD1 157 1.9 expression at 11 weeks of age (5.3-fold) 5.3-fold in G93A SOD1 mice which increased further at 14 and 17 weeks (8-fold) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122276 16510725 161092 18741 10289 RPA1 RPA RPAs 84 0.0 Elliott 2001 alpha receptors was also present A study using RPAs showed increased Fas-associated death domain (FADD) FADD and TNF-alpha receptor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122277 16510725 161093 22551 11892 TNF TNF-alpha TNF-alpha 7 1.7 Glial cells are the major source of TNF-alpha expression in the CNS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122278 16510725 161094 20996 11179 SOD1 SOD1 SOD1 13 1.9 both lumbar spinal cord motor neurons and glia from G93A SOD1 mice express high levels of TNF-alpha and this occurs at 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122279 16510725 161094 22551 11892 TNF TNF-alpha TNF-alpha 19 1.7 and glia from G93A SOD1 mice express high levels of TNF-alpha and this occurs at 60 d well before the onset 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122280 16510725 161096 22551 11892 TNF TNF-alpha TNF-alpha 3 1.7 An increase in TNF-alpha mRNA was confirmed by real-time RT-PCR in G93A mice at 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122281 16510725 161097 22551 11892 TNF TNF-alpha TNF-alpha 3 1.7 Double labeling of TNF-alpha with GFAP confirmed expression of TNF-alpha in astrocytes ( Fig 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122282 16510725 161097 8254 4235 GFAP GFAP GFAP 6 2.5 Double labeling of TNF-alpha with GFAP confirmed expression of TNF-alpha in astrocytes ( Fig 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122283 16510725 161097 22551 11892 TNF TNF-alpha TNF-alpha 10 1.7 Double labeling of TNF-alpha with GFAP confirmed expression of TNF-alpha in astrocytes ( Fig 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122284 16510725 161098 22551 11892 TNF TNF-alpha TNF-alpha 9 1.7 This is consistent with a previous study in which TNF-alpha immunoreactivity was increased at 17 weeks of age in microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122285 16510725 161098 20996 11179 SOD1 SOD1 SOD1 26 1.9 weeks of age in microglia and motor neurons of G93A SOD1 mice (Yoshihara Yoshihara et al. 2002 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122286 16510725 161099 7333 11920 FAS FAS Fas 0 2.1 Fas triggers cell death in embryonic motoneurons by a pathway requiring 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000487080126608893<>ScoreDetail__11920|FAS|0.000487080126608893__3594|FASN|0.000378882763346198__ 0 0 0 0 0 122287 16510725 161099 12359 6876 MAPK14 p38 p38 25 0.3 oxide synthase and involving Daxx apoptosis signal-regulated kinase 1 and p38 as well as the FADD/caspase-8 FADD caspase-8 pathway (Raoul Raoul 1 JUMiner_v2.2 1 0 0 2 6871 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6871|MAPK1|0.000373493635280144<>ScoreDetail__1189|AHSA1|2.59100919808265e-05__6878|MAPK4|0.000297040697351618__6871|MAPK1|0.000373493635280144__6876|MAPK14|0.00036158044131666__ 0 0 0 0 0 122288 16510725 161099 6920 3573 FADD FADD FADD 30 0.9 signal-regulated kinase 1 and p38 as well as the FADD/caspase-8 FADD caspase-8 pathway (Raoul Raoul et al. 2002 alpha upregulates FasL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122289 16510725 161099 3532 1509 CASP8 caspase-8 caspase-8 30 2.0 kinase 1 and p38 as well as the FADD/caspase-8 FADD caspase-8 pathway (Raoul Raoul et al. 2002 alpha upregulates FasL (Pinkoski 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122290 16510725 161099 7334 11936 FASLG FasL FasL 38 3.2 FADD caspase-8 pathway (Raoul Raoul et al. 2002 alpha upregulates FasL (Pinkoski Pinkoski et al. 2002 alpha immunostaining was found in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122291 16510725 161099 7334 11936 FASLG FasL FasL 55 3.2 was found in the neurons of adjacent sections suggesting that FasL and TNF-alpha are coexpressed in these neurons ( Fig 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122292 16510725 161099 22551 11892 TNF TNF-alpha TNF-alpha 57 1.7 in the neurons of adjacent sections suggesting that FasL and TNF-alpha are coexpressed in these neurons ( Fig 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122293 16510725 161099 5457 2681 DAXX DAXX Daxx 19 0.0 pathway requiring upregulation of neuronal nitric oxide synthase and involving Daxx apoptosis signal-regulated kinase 1 and p38 as well as the 2 JUMiner_v2.2 1 1 daxx; 0 0 0 0 0 0 0 0 122294 16510725 161100 22551 11892 TNF TNF-alpha TNF-alpha 2 1.7 Because both TNF-alpha and FasL immunostaining were increased in G93A mice we examined 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122295 16510725 161100 7334 11936 FASLG FasL FasL 5 3.2 Because both TNF-alpha and FasL immunostaining were increased in G93A mice we examined the effects 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122296 16510725 161100 22551 11892 TNF TNF-alpha TNF-alpha 27 1.7 thalidomide and its analog lenalidomide which inhibits the stability of TNF-alpha mRNA (Moreira Moreira et al. 1993 alpha and FasL expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122297 16510725 161100 7334 11936 FASLG FasL FasL 36 3.2 of TNF-alpha mRNA (Moreira Moreira et al. 1993 alpha and FasL expression in motor neurons of G93A mice There was a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122298 16510725 161100 20996 11179 SOD1 SOD1 SOD1 60 1.9 onset and a significant attenuation of disease progression in G93A SOD1 mice ( Figs 4 -6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122299 16510725 161102 22551 11892 TNF TNF-alpha TNF-alpha 10 1.7 Quantitative RT-PCR showed that both thalidomide and lenalidomide significantly reduced TNF-alpha mRNA levels at 110 d of age 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122300 16510725 161103 10437 5992 IL1B IL-1 IL-1 5 1.3 Both compounds also inhibited IL-12p40 IL-1 alpha and IL-1 beta 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122301 16510725 161103 10437 5992 IL1B IL-1 IL-1 8 1.3 Both compounds also inhibited IL-12p40 IL-1 alpha and IL-1 beta 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122302 16510725 161104 10444 5993 IL1R1 IL1RA IL-1RA 0 0.3 IL-1RA and TGF-beta1 mRNA were upregulated in G93A mice treated with 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000423659539306519<>ScoreDetail__5993|IL1R1|0.000382067915920541__6000|IL1RN|0.000423659539306519__ 0 0 0 0 0 122303 16510725 161104 22059 11766 TGFB1 TGFB1 TGF-beta1 2 0.1 IL-1RA and TGF-beta1 mRNA were upregulated in G93A mice treated with thalidomide and 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122304 16510725 161105 20996 11179 SOD1 ALS ALS 12 1.4 provide additional evidence for a role of pro-inflammatory cytokines in ALS and suggest that TNF-alpha and FasL and related cytokines have 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122305 16510725 161105 22551 11892 TNF TNF-alpha TNF-alpha 16 1.7 a role of pro-inflammatory cytokines in ALS and suggest that TNF-alpha and FasL and related cytokines have important triggering roles in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122306 16510725 161105 7334 11936 FASLG FasL FasL 19 3.2 of pro-inflammatory cytokines in ALS and suggest that TNF-alpha and FasL and related cytokines have important triggering roles in the pathogenesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122307 16510725 161105 20996 11179 SOD1 ALS ALS 31 1.4 related cytokines have important triggering roles in the pathogenesis of ALS in initiating a cell death pathway(s) pathway s 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122308 16510725 161106 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha binds to TNF receptor-1 and activates it to ligate with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122309 16510725 161106 22551 11892 TNF TNF TNF 4 1.7 TNF-alpha binds to TNF receptor-1 and activates it to ligate with TNF-alpha receptor-associated death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122310 16510725 161106 22551 11892 TNF TNF-alpha TNF-alpha 12 1.7 binds to TNF receptor-1 and activates it to ligate with TNF-alpha receptor-associated death domain (TRADD), TRADD forming the DISC that leads 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122311 16510725 161106 22735 12030 TRADD TRADD TRADD 17 0.6 activates it to ligate with TNF-alpha receptor-associated death domain (TRADD), TRADD forming the DISC that leads to activation of caspase-8 resulting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122312 16510725 161106 3532 1509 CASP8 caspase-8 caspase-8 26 2.0 (TRADD), TRADD forming the DISC that leads to activation of caspase-8 resulting in Bid cleavage and the activation of executioner caspases-3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122313 16510725 161107 7334 11936 FASLG FasL FasL 0 3.2 FasL works in a similar way by binding to Fas/CD95 Fas 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122314 16510725 161107 7333 11920 FAS FAS Fas 9 2.1 FasL works in a similar way by binding to Fas/CD95 Fas CD95 receptor and activate it to cause FADD ligation and 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000487080126608893<>ScoreDetail__11920|FAS|0.000487080126608893__3594|FASN|0.000378882763346198__ 0 0 0 0 0 122315 16510725 161107 7333 11920 FAS CD95 CD95 9 2.1 works in a similar way by binding to Fas/CD95 Fas CD95 receptor and activate it to cause FADD ligation and DISC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122316 16510725 161107 6920 3573 FADD FADD FADD 16 0.9 to Fas/CD95 Fas CD95 receptor and activate it to cause FADD ligation and DISC formation which also leads on to caspase-8 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122317 16510725 161107 3532 1509 CASP8 caspase-8 caspase-8 26 2.0 FADD ligation and DISC formation which also leads on to caspase-8 activation Bid cleavage and ultimately activation of caspases-3 -6 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122318 16510725 161108 3532 1509 CASP8 caspase-8 caspase-8 6 2.0 Because these two pathways converge on caspase-8 activation they may have synergistic effects 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122319 16510725 161109 20996 11179 SOD1 ALS ALS 18 1.4 and lenalidomide may have therapeutic value for treatment of human ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122320 16510725 161111 22551 11892 TNF TNF-alpha TNF-alpha 2 1.7 Lenalidomide inhibited TNF-alpha with less potency compared with thalidomide in contrast lenalidomide was 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122321 16510725 161111 10437 5992 IL1B IL-1 IL-1 23 1.3 was more potent in inhibiting other cytokines such as IL-12p40 IL-1 alpha and IL-1 beta 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122322 16510725 161111 10437 5992 IL1B IL-1 IL-1 26 1.3 in inhibiting other cytokines such as IL-12p40 IL-1 alpha and IL-1 beta 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122323 16510725 161113 20996 11179 SOD1 ALS ALS 33 1.4 one or several pathways to cause motor neuron degeneration in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122324 16510725 161114 10444 5993 IL1R1 IL1RA IL-1RA 12 0.3 and lenalidomide are able to upregulate anti-inflammatory cytokines such as IL-1RA and TGF-beta1 which may have neuroprotective effects 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000423659539306519<>ScoreDetail__5993|IL1R1|0.000382067915920541__6000|IL1RN|0.000423659539306519__ 0 0 0 0 0 122325 16510725 161114 22059 11766 TGFB1 TGFB1 TGF-beta1 14 0.1 are able to upregulate anti-inflammatory cytokines such as IL-1RA and TGF-beta1 which may have neuroprotective effects 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122326 16510725 161117 22551 11892 TNF TNF-alpha TNF-alpha 10 1.7 In both erythema nodosum leprosum and myelodysplastic syndromes upregulation of TNF-alpha production is postulated to contribute to disease pathogenesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122327 16510725 161119 22551 11892 TNF TNF-alpha TNF-alpha 5 1.7 The suppression of spinal cord TNF-alpha mRNA in our study by thalidomide and lenalidomide hence extension 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122328 16510725 161120 20996 11179 SOD1 ALS ALS 13 1.4 therefore have promise as therapeutic agents for the treatment of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122329 16510725 161122 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha immunoreactivity in G93A SOD1 and control mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122330 16510725 161122 20996 11179 SOD1 SOD1 SOD1 5 1.9 TNF-alpha immunoreactivity in G93A SOD1 and control mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122331 16510725 161123 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha immunoreactivity was examined in the spinal cords of transgenic G93A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122332 16510725 161123 20996 11179 SOD1 SOD1 SOD1 12 1.9 immunoreactivity was examined in the spinal cords of transgenic G93A SOD1 mice at 40 60 90 and 110 d of age 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122333 16510725 161123 20996 11179 SOD1 SOD1 hSOD1 28 1.4 and 110 d of age and in 110-d-old transgenic wild-type hSOD1 (N1029) N1029 control mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122334 16510725 161124 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha immunoreactivity is seen in the anterior horn motor neurons (arrows), 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122335 16510725 161125 22551 11892 TNF TNF-alpha TNF-alpha 3 1.7 Thalidomide treatment reduced TNF-alpha immunoreactivity (middle middle row left panel 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122336 16510725 161126 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha double immunofluorescence with GFAP showed that TNF-alpha colocalizes with GFAP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122337 16510725 161126 8254 4235 GFAP GFAP GFAP 5 2.5 TNF-alpha double immunofluorescence with GFAP showed that TNF-alpha colocalizes with GFAP in astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122338 16510725 161126 22551 11892 TNF TNF-alpha TNF-alpha 8 1.7 TNF-alpha double immunofluorescence with GFAP showed that TNF-alpha colocalizes with GFAP in astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122339 16510725 161126 8254 4235 GFAP GFAP GFAP 12 2.5 TNF-alpha double immunofluorescence with GFAP showed that TNF-alpha colocalizes with GFAP in astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122340 16510725 161127 22551 11892 TNF TNF-alpha TNF-alpha 9 1.7 The white arrowhead points to an astrocyte labeled with TNF-alpha (green) green and GFAP (red) red and colocalization of TNF-alpha 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122341 16510725 161127 8254 4235 GFAP GFAP GFAP 13 2.5 points to an astrocyte labeled with TNF-alpha (green) green and GFAP (red) red and colocalization of TNF-alpha and GFAP (yellow) yellow 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122342 16510725 161127 22551 11892 TNF TNF-alpha TNF-alpha 18 1.7 TNF-alpha (green) green and GFAP (red) red and colocalization of TNF-alpha and GFAP (yellow) yellow 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122343 16510725 161127 8254 4235 GFAP GFAP GFAP 21 2.5 green and GFAP (red) red and colocalization of TNF-alpha and GFAP (yellow) yellow 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122344 16510725 161130 7334 11936 FASLG FasL FasL 0 3.2 FasL immunoreactivity in G93A SOD1 and control mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122345 16510725 161130 20996 11179 SOD1 SOD1 SOD1 4 1.9 FasL immunoreactivity in G93A SOD1 and control mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122346 16510725 161131 7334 11936 FASLG FasL FasL 0 3.2 FasL immunoreactivity in neurons of the ventral horn of the lumbar 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122347 16510725 161132 7334 11936 FASLG FasL FasL 2 3.2 Increases in FasL staining in neurons (arrowheads) arrowheads and neuronal processes occurred as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122348 16510725 161134 7334 11936 FASLG FasL FasL 3 3.2 Thalidomide treatment reduced FasL immunoreactivity (middle middle row left panel 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122349 16510725 161135 7334 11936 FASLG FasL FasL 0 3.2 FasL double immunofluorescence with GFAP showed that FasL colocalizes with GFAP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122350 16510725 161135 8254 4235 GFAP GFAP GFAP 4 2.5 FasL double immunofluorescence with GFAP showed that FasL colocalizes with GFAP in astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122351 16510725 161135 7334 11936 FASLG FasL FasL 7 3.2 FasL double immunofluorescence with GFAP showed that FasL colocalizes with GFAP in astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122352 16510725 161135 8254 4235 GFAP GFAP GFAP 10 2.5 FasL double immunofluorescence with GFAP showed that FasL colocalizes with GFAP in astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122353 16510725 161136 7334 11936 FASLG FasL FasL 8 3.2 The white arrows point to astrocytes labeled with FasL (green) green and GFAP (red) red and colocalization of FasL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122354 16510725 161136 8254 4235 GFAP GFAP GFAP 11 2.5 arrows point to astrocytes labeled with FasL (green) green and GFAP (red) red and colocalization of FasL and GFAP (yellow) yellow 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122355 16510725 161136 7334 11936 FASLG FasL FasL 16 3.2 FasL (green) green and GFAP (red) red and colocalization of FasL and GFAP (yellow) yellow 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122356 16510725 161136 8254 4235 GFAP GFAP GFAP 18 2.5 green and GFAP (red) red and colocalization of FasL and GFAP (yellow) yellow 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122357 16510725 161139 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha and FasL immunoreactivity in human ALS and controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122358 16510725 161139 7334 11936 FASLG FasL FasL 3 3.2 TNF-alpha and FasL immunoreactivity in human ALS and controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122359 16510725 161139 20996 11179 SOD1 ALS ALS 7 1.4 TNF-alpha and FasL immunoreactivity in human ALS and controls 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122360 16510725 161140 7334 11936 FASLG FasL FasL 0 3.2 FasL (top top panels and TNF-alpha (bottom bottom panels immunoreactivities in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122361 16510725 161140 22551 11892 TNF TNF-alpha TNF-alpha 4 1.7 FasL (top top panels and TNF-alpha (bottom bottom panels immunoreactivities in the lumbar ventral horn of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122362 16510725 161140 20996 11179 SOD1 ALS ALS 20 1.4 the lumbar ventral horn of the spinal cord of human ALS and control patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122363 16510725 161141 22551 11892 TNF TNF-alpha TNF-alpha- 2 1.7 We found TNF-alpha- and FasL-immunoreactive neurons in the lumbar spinal cord sections of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122364 16510725 161141 7334 11936 FASLG FasL FasL-immunoreactive 5 2.7 We found TNF-alpha- and FasL-immunoreactive neurons in the lumbar spinal cord sections of a familial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122365 16510725 161141 20996 11179 SOD1 ALS ALS 16 1.4 neurons in the lumbar spinal cord sections of a familial ALS patient with SOD1 mutation (I113T) I113T and sporadic ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122366 16510725 161141 20996 11179 SOD1 SOD1 SOD1 19 1.9 lumbar spinal cord sections of a familial ALS patient with SOD1 mutation (I113T) I113T and sporadic ALS patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122367 16510725 161141 20996 11179 SOD1 ALS ALS 24 1.4 familial ALS patient with SOD1 mutation (I113T) I113T and sporadic ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122368 16510725 161142 22551 11892 TNF TNF-alpha TNF-alpha 1 1.7 Intense TNF-alpha and FasL immunoreactivity occurred predominantly in neurons of ALS patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122369 16510725 161142 7334 11936 FASLG FasL FasL 4 3.2 Intense TNF-alpha and FasL immunoreactivity occurred predominantly in neurons of ALS patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122370 16510725 161142 20996 11179 SOD1 ALS ALS 11 1.4 Intense TNF-alpha and FasL immunoreactivity occurred predominantly in neurons of ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122371 16510725 161143 22551 11892 TNF TNF-alpha TNF-alpha 2 1.7 Coexistence of TNF-alpha and FasL occurred in the same neurons in adjacent sections 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122372 16510725 161143 7334 11936 FASLG FasL FasL 5 3.2 Coexistence of TNF-alpha and FasL occurred in the same neurons in adjacent sections of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122373 16510725 161143 20996 11179 SOD1 ALS ALS 15 1.4 FasL occurred in the same neurons in adjacent sections of ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122374 16510725 161146 20996 11179 SOD1 SOD1 SOD1 12 1.9 of thalidomide or lenalidomide treatment on motor performance in G93A SOD1 transgenic mice from 89 to 165 d of age 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122375 16510725 161148 20996 11179 SOD1 SOD1 SOD1 20 1.9 mg kg thalidomide 100 mg/kg mg kg lenalidomide vehicle-treated G93A SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122376 16510725 161153 20996 11179 SOD1 SOD1 SOD1 20 1.9 mg kg thalidomide 100 mg/kg mg kg lenalidomide vehicle-treated G93A SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122377 16510725 161155 20996 11179 SOD1 SOD1 SOD1 16 1.9 (Lenali) Lenali treatment on Nissl-stained neuronal cell counts in G93A SOD1 transgenic mice at 110 d of age 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122378 16510725 161161 22551 11892 TNF TNF-alpha TNF-alpha 3 1.7 Real-time RT-PCR for TNF-alpha expression in the spinal cord tissue of G93A SOD1 control 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122379 16510725 161161 20996 11179 SOD1 SOD1 SOD1 13 1.9 for TNF-alpha expression in the spinal cord tissue of G93A SOD1 control mice and G93A mice treated with thalidomide or lenalidomide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122380 16510725 161162 22551 11892 TNF TNF-alpha TNF-alpha 3 1.7 The amount of TNF-alpha cDNA was measured in the total cDNA made from total 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122381 16510725 161162 20996 11179 SOD1 SOD1 SOD1 27 1.9 cord tissue of 110-d-old N1029/B6SJL N1029 B6SJL controls and G93A SOD1 mice treated with vehicle thalidomide or lenalidomide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122382 16510725 161163 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha cDNA amount in different samples was normalized against GAPDH cDNA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122383 16510725 161163 8118 4141 GAPDH GAPDH GAPDH 10 1.6 TNF-alpha cDNA amount in different samples was normalized against GAPDH cDNA and expressed as a percentage of GAPDH cDNA (** 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122384 16510725 161163 8118 4141 GAPDH GAPDH GAPDH 18 1.6 normalized against GAPDH cDNA and expressed as a percentage of GAPDH cDNA (** ** p _lt_ 0.01 *** p _lt_ 0.0005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122385 16510725 161164 8118 4141 GAPDH GAPDH GAPDH 5 1.6 There were no changes in GAPDH cDNA amount among the groups 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122386 16510725 161168 10437 5992 IL1B IL-1 IL-1 14 1.3 RNA was used against a RPA multiprobe of cytokines a IL-1 alpha RNA was elevated in vehicle-treated G93A mice compared with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122387 16510725 161168 10437 5992 IL1B IL-1 IL-1 44 1.3 lenalidomide-treated G93A mice while unchanged in thalidomide-treated G93A mice b IL-1 beta RNA was elevated in vehicle-treated G93A mice compared with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122388 16510725 161168 10444 5993 IL1R1 IL1RA IL-1RA 97 0.3 significantly reduced in both lenalidomide- and thalidomide-treated G93A mice d IL-1RA RNA was elevated in vehicle-treated G93A mice compared with wild 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000423659539306519<>ScoreDetail__5993|IL1R1|0.000382067915920541__6000|IL1RN|0.000423659539306519__ 0 0 0 0 0 122389 16510725 161168 18741 10289 RPA1 RPA RPA 8 0.0 Spinal cord total RNA was used against a RPA multiprobe of cytokines a IL-1 alpha RNA was elevated in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122390 16510725 161168 22059 11766 TGFB1 TGFB1 TGF-beta1 124 0.0 elevated further in both lenalidomide- and thalidomide-treated G93A mice e TGF-beta1 RNA was not changed significantly in vehicle-treated G93A mice compared 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122391 16510725 161169 8118 4141 GAPDH GAPDH GAPDH 11 1.6 RNA amounts in different samples were normalized against (L32 L32 GAPDH RNA multiplied by 1000 and presented as an arbitrary number 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122392 16510725 161169 8118 4141 GAPDH GAPDH GAPDH 25 1.6 1000 and presented as an arbitrary number per (L32 L32 GAPDH RNA (* * p _lt_ 0.5 ** p _lt_ 0.05 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122393 16510725 161172 7334 11936 FASLG FasL FasL 3 3.2 Strong immunoreactivity for FasL was evident in neurons as early as 40 d 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122394 16510725 161173 7334 11936 FASLG FasL FasL 1 3.2 However FasL immunoreactivity was less pronounced at 110 d ( Fig 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122395 16510725 161174 22551 11892 TNF TNF-alpha TNF-alpha 1 1.7 Both TNF-alpha and FasL immunoreactivity persisted relatively strong in the lumbar spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122396 16510725 161174 7334 11936 FASLG FasL FasL 4 3.2 Both TNF-alpha and FasL immunoreactivity persisted relatively strong in the lumbar spinal cord sections 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122397 16510725 161175 7334 11936 FASLG FasL FasL 4 3.2 We also examined the FasL immunoreactivity in astrocytes by double labeling with the astrocyte marker 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122398 16510725 161175 8254 4235 GFAP GFAP GFAP 15 2.5 immunoreactivity in astrocytes by double labeling with the astrocyte marker GFAP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122399 16510725 161176 7334 11936 FASLG FasL FasL 0 3.2 FasL immunoreactivity colocalized with GFAP indicating that FasL immunostaining was found 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122400 16510725 161176 8254 4235 GFAP GFAP GFAP 4 2.5 FasL immunoreactivity colocalized with GFAP indicating that FasL immunostaining was found in both neurons and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122401 16510725 161176 7334 11936 FASLG FasL FasL 7 3.2 FasL immunoreactivity colocalized with GFAP indicating that FasL immunostaining was found in both neurons and astrocytes similar to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122402 16510725 161176 22551 11892 TNF TNF TNF-alpha. 18 1.7 immunostaining was found in both neurons and astrocytes similar to TNF-alpha. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122403 16510725 161177 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha and FasL immunoreactivity in human ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122404 16510725 161177 7334 11936 FASLG FasL FasL 3 3.2 TNF-alpha and FasL immunoreactivity in human ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122405 16510725 161177 20996 11179 SOD1 ALS ALS 7 1.4 TNF-alpha and FasL immunoreactivity in human ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122406 16510725 161178 20996 11179 SOD1 ALS ALS 6 1.4 Consistent with the immunohistochemical findings in ALS transgenic mice intense TNF-alpha and FasL immunoreactivity occurred in the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122407 16510725 161178 22551 11892 TNF TNF-alpha TNF-alpha 10 1.7 Consistent with the immunohistochemical findings in ALS transgenic mice intense TNF-alpha and FasL immunoreactivity occurred in the lumbar spinal cord sections 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122408 16510725 161178 7334 11936 FASLG FasL FasL 13 3.2 the immunohistochemical findings in ALS transgenic mice intense TNF-alpha and FasL immunoreactivity occurred in the lumbar spinal cord sections from an 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122409 16510725 161178 20996 11179 SOD1 ALS ALS 24 1.4 immunoreactivity occurred in the lumbar spinal cord sections from an ALS patient with a SOD1 mutation (I113T) I113T as well as 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122410 16510725 161178 20996 11179 SOD1 SOD1 SOD1 28 1.9 lumbar spinal cord sections from an ALS patient with a SOD1 mutation (I113T) I113T as well as sporadic ALS patients whereas 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122411 16510725 161178 20996 11179 SOD1 ALS ALS 35 1.4 with a SOD1 mutation (I113T) I113T as well as sporadic ALS patients whereas control tissues showed very little or no TNF-alpha 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 122412 16510725 161178 22551 11892 TNF TNF-alpha TNF-alpha 45 1.7 ALS patients whereas control tissues showed very little or no TNF-alpha and FasL immunoreactivity ( Fig 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122413 16510725 161178 7334 11936 FASLG FasL FasL 48 3.2 whereas control tissues showed very little or no TNF-alpha and FasL immunoreactivity ( Fig 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122414 16510725 161179 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha and FasL coexisted in the motor neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122415 16510725 161179 7334 11936 FASLG FasL FasL 3 3.2 TNF-alpha and FasL coexisted in the motor neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122416 16510725 161187 22551 11892 TNF TNF-alpha TNF-alpha 16 1.7 in survival was associated with a marked dose-dependent decrease in TNF-alpha immunoreactivity in the motor neurons and glial cells in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122417 16510725 161188 22551 11892 TNF TNF-alpha TNF-alpha 6 1.7 We show that thalidomide treatment reduced TNF-alpha and FasL immunoreactivity in the spinal cords of G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122418 16510725 161188 7334 11936 FASLG FasL FasL 9 3.2 We show that thalidomide treatment reduced TNF-alpha and FasL immunoreactivity in the spinal cords of G93A mice ( Figs 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122419 16510725 161198 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha mRNA in G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122420 16510725 161199 22551 11892 TNF TNF-alpha TNF-alpha 3 1.7 To determine whether TNF-alpha mRNA is upregulated and whether thalidomide and lenalidomide can block 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122421 16510725 161199 20996 11179 SOD1 SOD1 SOD1 43 1.9 from total RNA extracted from the spinal cords of G93A SOD1 mice treated with thalidomide or lenalidomide vehicle-treated G93A mice and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122422 16510725 161199 20996 11179 SOD1 SOD1 SOD1 57 1.9 or lenalidomide vehicle-treated G93A mice and N1029 mice (wild-type wild-type SOD1 overexpressers at 110 d of age 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122423 16510725 161200 22551 11892 TNF TNF-alpha TNF-alpha 0 1.7 TNF-alpha mRNA was increased 10-fold in G93A SOD1 mice compared with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122424 16510725 161200 20996 11179 SOD1 SOD1 SOD1 8 1.9 TNF-alpha mRNA was increased 10-fold in G93A SOD1 mice compared with control littermates ( p _lt_ 0.005 ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122425 16510725 161201 22551 11892 TNF TNF-alpha TNF-alpha 5 1.7 Thalidomide and lenalidomide treatment reduced TNF-alpha mRNA significantly ( p _lt_ 0.01 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122426 16510725 161202 18741 10289 RPA1 RPA RPAs 4 0.0 Cytokine levels by multiprobe RPAs 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122427 16510725 161203 18741 10289 RPA1 RPA RPA 22 0.0 G93A mice at 110 d of age were subjected to RPA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122428 16510725 161204 10444 5993 IL1R1 IL1RA IL-1RA 15 0.3 lenalidomide downregulated interleukin (IL)-12p40 IL -12p40 and upregulated TGF-beta1 and IL-1RA in treated G93A mice compared with vehicle-treated G93A mice ( 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000423659539306519<>ScoreDetail__5993|IL1R1|0.000382067915920541__6000|IL1RN|0.000423659539306519__ 0 0 0 0 0 122429 16510725 161204 18741 10289 RPA1 RPA RPA 0 0.0 RPA showed that both thalidomide and lenalidomide downregulated interleukin (IL)-12p40 IL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122430 16510725 161204 22059 11766 TGFB1 TGFB1 TGF-beta1 12 0.0 thalidomide and lenalidomide downregulated interleukin (IL)-12p40 IL -12p40 and upregulated TGF-beta1 and IL-1RA in treated G93A mice compared with vehicle-treated G93A 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122431 16510725 161205 10437 5992 IL1B IL-1 IL-1 3 1.3 Lenalidomide also downregulated IL-1 alpha and IL-1 beta 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122432 16510725 161205 10437 5992 IL1B IL-1 IL-1 6 1.3 Lenalidomide also downregulated IL-1 alpha and IL-1 beta 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122433 16510725 161206 10480 5962 IL10 IL-10 IL-10 6 1.3 No changes were detected in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122434 16510725 161206 10508 5986 IL18 IL-18 IL-18 7 1.3 No changes were detected in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT alpha 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122435 16510725 161206 9905 5438 IFNG IFN IFN 8 0.3 No changes were detected in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT alpha or 1 JUMiner_v2.2 1 0 0 2 5438 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5438|IFNG|0.000424356799487002<>ScoreDetail__5438|IFNG|0.000424356799487002__5417|IFNA1|0.000422141097942281__ 0 0 0 0 0 122436 16510725 161206 9905 5438 IFNG IFN IFN 11 0.3 changes were detected in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT alpha or LT beta (data 1 JUMiner_v2.2 1 0 0 2 5438 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5438|IFNG|0.000424356799487002<>ScoreDetail__5438|IFNG|0.000424356799487002__5417|IFNA1|0.000422141097942281__ 0 0 0 0 0 122437 16510725 161206 10463 6018 IL6 IL-6 IL-6 13 1.3 detected in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT alpha or LT beta (data data not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122438 16510725 161206 22062 11769 TGFB3 TGF-beta3 TGF-beta3 14 0.2 in IL-12p35 IL-10 IL-18 IFN gamma or IFN beta IL-6 TGF-beta3 and LT alpha or LT beta (data data not shown 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 122439 16510725 161210 20996 11179 SOD1 ALS ALS 8 1.4 We thank Dr A Hays for providing human ALS spinal cord samples 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0011541420877148<>ScoreDetail__5468|IGFALS|0.000575879295699621__11179|SOD1|0.0011541420877148__ 0 0 0 0 0 109232 16533145 142006 20996 11179 SOD1 ALS ALS 4 1.9 Although amyotrophic lateral sclerosis (ALS) ALS was described more than 130 years ago the cause(s) cause 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00141825132207281<>ScoreDetail__5468|IGFALS|0.000434480361487661__11179|SOD1|0.00141825132207281__ 0 0 0 0 0 109233 16533145 142007 20996 11179 SOD1 ALS ALS 19 1.9 superoxide dismutase as a primary cause of some forms of ALS model systems have been developed that have helped us begin 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00141825132207281<>ScoreDetail__5468|IGFALS|0.000434480361487661__11179|SOD1|0.00141825132207281__ 0 0 0 0 0 113036 16624536 146803 20996 11179 SOD1 ALS ALS 3 1.7 Amyotrophic lateral sclerosis (ALS) ALS is a fatal neurodegenerative condition in which motor neurons are 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113037 16624536 146805 20996 11179 SOD1 ALS ALS 14 1.7 motor neuron loss is evident in presymptomatic mouse models of ALS and in human patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113038 16624536 146806 20996 11179 SOD1 ALS ALS 8 1.7 Efforts aimed at attenuating the inflammatory response in ALS animal models have delayed symptom onset and extended survival 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113039 16624536 146809 20996 11179 SOD1 ALS ALS 1 1.7 Because ALS is a syndromic disease in which glutamate excitotoxicity altered cytoskeletal 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113040 16624536 146824 20996 11179 SOD1 ALS ALS 3 1.7 Amyotrophic lateral sclerosis (ALS) ALS is a fatal neurodegenerative disease characterized by the selective loss 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113041 16624536 146828 20996 11179 SOD1 ALS ALS 6 1.7 While between 5 and 8% of ALS cases are familial (fALS), fALS of which 20% harbour missense 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113042 16624536 146828 20996 11179 SOD1 SOD1 SOD1 22 1.7 harbour missense mutations in the copper_amp_#x2013 zinc superoxide dismutase (SOD1) SOD1 gene 3 the majority of ALS cases are sporadic (sALS) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113043 16624536 146828 20996 11179 SOD1 ALS ALS 29 1.7 zinc superoxide dismutase (SOD1) SOD1 gene 3 the majority of ALS cases are sporadic (sALS) sALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113044 16624536 146829 20996 11179 SOD1 ALS ALS 4 1.7 Although the etiology of ALS remains to be defined the contemporary understanding of ALS is 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113045 16624536 146829 20996 11179 SOD1 ALS ALS 13 1.7 of ALS remains to be defined the contemporary understanding of ALS is that it is likely syndromic as opposed to a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113046 16624536 146830 20996 11179 SOD1 ALS ALS 7 1.7 Key components of the pathological process of ALS include glutamate excitotoxicity disturbances in cytoskeletal protein metabolism (e.g., e.g. 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113047 16624536 146844 22551 11892 TNF TNF TNF 19 0.3 astrocytes including interferon _amp_#x3b3 (IFN_amp_#x3b3;), IFN_amp_#x3b3 tumour necrosis factor (TNF TNF macrophage colony stimulating factor (M-CSF), M-CSF and granulocyte macrophage colony 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113048 16624536 146844 5008 2432 CSF1 M-CSF M-CSF 25 1.2 tumour necrosis factor (TNF TNF macrophage colony stimulating factor (M-CSF), M-CSF and granulocyte macrophage colony stimulating factor (GM-CSF) GM-CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113049 16624536 146844 5010 2434 CSF2 GM-CSF GM-CSF 32 2.2 factor (M-CSF), M-CSF and granulocyte macrophage colony stimulating factor (GM-CSF) GM-CSF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113050 16624536 146846 9353 4931 HLA-A MHC MHC 7 1.2 In this state they express major histocompatibility (MHC) MHC class II molecules and present antigens 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113051 16624536 146847 10437 5992 IL1B IL-1 IL-1 8 1.3 In response to secondary stimuli such as interleukin-1 (IL-1), IL-1 IL-6 and TNF- microglia exert maximal activity through secretion of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113052 16624536 146847 10463 6018 IL6 IL-6 IL-6 9 1.6 In response to secondary stimuli such as interleukin-1 (IL-1), IL-1 IL-6 and TNF- microglia exert maximal activity through secretion of inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113053 16624536 146847 22551 11892 TNF TNF TNF- 11 0.3 to secondary stimuli such as interleukin-1 (IL-1), IL-1 IL-6 and TNF- microglia exert maximal activity through secretion of inflammatory mediators ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113054 16624536 146851 20996 11179 SOD1 ALS ALS 30 1.7 to understanding the role of the innate immune response in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113055 16624536 146852 20996 11179 SOD1 SOD1 SOD1 28 1.7 of motor neuron degeneration in which the fALS associated G93A SOD1 mutation is expressed is dependant on the extent of non-neuronal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113056 16624536 146856 20996 11179 SOD1 SOD1 SOD1 15 1.7 recent work suggests the robust inflammatory response observed in symptomatic SOD1 G93A transgenic mice is mostly attributable to proliferation of resident 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113057 16624536 146858 20996 11179 SOD1 ALS ALS 2 1.7 Microglia in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113058 16624536 146859 20996 11179 SOD1 ALS ALS 15 1.7 neurochemical evidence for the proliferation and activation of microglia in ALS 15 16 17 18 19 20 21 22 23 24 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113059 16624536 146862 5008 2432 CSF1 M-CSF M-CSF 10 1.2 constitutively expressed in the human brain macrophage-colony stimulating factor (M-CSF) M-CSF receptor expression is upregulated in ALS precentral gyrus 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113060 16624536 146862 20996 11179 SOD1 ALS ALS 16 1.7 macrophage-colony stimulating factor (M-CSF) M-CSF receptor expression is upregulated in ALS precentral gyrus 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113061 16624536 146863 22551 11892 TNF TNF TNF- 1 0.3 Both TNF- and the soluble extracellular domains of its receptors TNFRI and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113062 16624536 146863 20996 11179 SOD1 ALS ALS 16 1.7 domains of its receptors TNFRI and TNFRII are increased in ALS serum 27 and 28 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113063 16624536 146864 17610 9605 PTGS2 COX-2 COX-2 6 1.5 An increased expression of pro-inflammatory cytokines COX-2 29 30 and 31 and of microglia-mediated protein oxidative pathology 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113064 16624536 146864 20996 11179 SOD1 ALS ALS 23 1.7 of microglia-mediated protein oxidative pathology 32 is also observed in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113065 16624536 146865 20996 11179 SOD1 ALS ALS 12 1.7 issue as to when in the course of degeneration in ALS that microglial activation becomes prominent is being addressed through neuroimaging 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113066 16624536 146866 20996 11179 SOD1 ALS ALS 33 1.7 of microglia microglial activation can be observed in patients with ALS 33 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113067 16624536 146868 20996 11179 SOD1 ALS ALS 28 1.7 possibility that microglial activation occurs early in the pathogenesis of ALS ( Fig 2 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113068 16624536 146869 7333 11920 FAS FAS Fas 25 0.6 motor neuron death via TNF--mediated apoptotic mechanisms 35 and by Fas ligand or NO-induced apoptotic pathways 36 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000978468419997679<>ScoreDetail__11920|FAS|0.000978468419997679__3594|FASN|0.000566946990456392__ 0 0 0 0 0 113069 16624536 146870 20996 11179 SOD1 SOD1 SOD1 10 1.7 It has also been demonstrated that microglia derived from mutant SOD1 transgenic mice have increased cytotoxic potential in culture 37 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113070 16624536 146871 20996 11179 SOD1 SOD1 SOD1 4 1.7 Using a chimeric mutant SOD1 model in which only a proportion of cells express the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113071 16624536 146872 20996 11179 SOD1 SOD1 SOD1 13 1.7 model non-transgenic motor neurons surrounded by glia expressing the mutant SOD1 transgene degenerated while transgenic motor neurons surrounded by non-transgenic glia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113072 16624536 146873 20996 11179 SOD1 SOD1 SOD1 4 1.7 This study suggests that SOD1 mutations once thought to selectively confer motor neuron susceptibility can 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113073 16624536 146874 20996 11179 SOD1 SOD1 SOD1 15 1.7 from Don Cleveland's group suggesting that genetic knock-down of mutant SOD1 in cells of the macrophage lineage can significantly slow the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113074 16624536 146874 20996 11179 SOD1 ALS ALS 28 1.7 of the macrophage lineage can significantly slow the progression of ALS 38 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113075 16624536 146875 20996 11179 SOD1 SOD1 SOD1 19 1.7 neurons such as the skeletal muscle will also express mutant SOD1 and could contribute to the health of motor neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113076 16624536 146876 20996 11179 SOD1 ALS ALS 37 1.7 and the rate of propagation of motor neuron degeneration in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113077 16624536 146877 20996 11179 SOD1 SOD1 SOD1 9 1.7 In contrast to these studies transgenic mice in which SOD1 G37R expression is driven by the mouse prion promoter resulting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113078 16624536 146877 20996 11179 SOD1 SOD1 SOD1 24 1.7 by the mouse prion promoter resulting in levels of mutant SOD1 expression highest in neurons and astrocytes in the CNS and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113079 16624536 146880 20996 11179 SOD1 ALS ALS 20 1.7 between inflammation and the progression of motor neuron disease in ALS arises from the study of murine models of motor neuron 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113080 16624536 146881 20996 11179 SOD1 SOD1 SOD1 4 1.7 In both the mutant SOD1 transgenic mice and rat an alteration in the expression and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113081 16624536 146882 5008 2432 CSF1 M-CSF M-CSF 4 1.2 Specifically both TGF-_amp_#x3b2 1 and M-CSF expression are upregulated in presymptomatic mice with TNF-expression being increased 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113082 16624536 146882 22551 11892 TNF TNF TNF-expression 12 0.3 1 and M-CSF expression are upregulated in presymptomatic mice with TNF-expression being increased well in advance of the appearance of motor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113083 16624536 146884 17610 9605 PTGS2 COX-2 COX-2 9 1.5 This process is associated with an increased level of COX-2 mRNA and protein and an increase in PGE 2 content 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113084 16624536 146885 17610 9605 PTGS2 COX-2 COX-2 28 1.5 excitotoxicity in organotypic spinal cord cultures can be suppressed by COX-2 inhibition 52 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113085 16624536 146886 10676 6121 IRF6 LPS LPS 11 0.6 neuron disease is accelerated by chronic stimulation of inflammation using LPS in the SOD1 G37R mouse model of ALS with increasing 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 113086 16624536 146886 20996 11179 SOD1 SOD1 SOD1 14 1.7 accelerated by chronic stimulation of inflammation using LPS in the SOD1 G37R mouse model of ALS with increasing levels of pro-inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113087 16624536 146886 20996 11179 SOD1 ALS ALS 19 1.7 inflammation using LPS in the SOD1 G37R mouse model of ALS with increasing levels of pro-inflammatory cytokines and increased expression of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113088 16624536 146886 22217 11848 TLR2 TLR2 TLR-2 33 1.6 pro-inflammatory cytokines and increased expression of toll-like receptor 2 (TLR-2) TLR-2 53 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113089 16624536 146893 22551 11892 TNF TNF TNF- 23 0.3 induces neurotoxicity in primary cortical neurons via coincident stimulation of TNF- and NMDA receptors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113090 16624536 146894 22551 11892 TNF TNF TNF- 3 0.3 Stimulation of either TNF- or NMDA receptors alone does not initiate cell death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113091 16624536 146895 22561 11916 TNFRSF1A TNF-R TNF-receptor 9 1.8 Memantine and 2-amino-5-phosphopetanoic acid NMDA receptor antagonists and soluble TNF-receptor protect neurons from microglial-conditioned media-dependent death which is thought to 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113092 16624536 146895 14535 7873 NOS2A iNOS iNOS 31 2.7 from oxidative damage resulting from inducible nitric oxide synthase (iNOS) iNOS activity 59 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113093 16624536 146896 6554 3309 ELA2 HNE HNE 12 0.0 can be triggered by oxidative injury mediated through hydroxynonenal (HNE) HNE formation and the triggering of apoptosis 60 suggesting that another 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113094 16624536 146897 20996 11179 SOD1 ALS ALS 31 1.7 neuron cell line an important consideration in the context of ALS is the selective vulnerability of motor neurons in vivo 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113095 16624536 146898 20996 11179 SOD1 SOD1 SOD1 5 1.7 Motor neurons derived from mutant SOD1 transgenic mice exhibit an increased susceptibility to activation of a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113096 16624536 146898 7333 11920 FAS FAS Fas-triggered 16 0.6 transgenic mice exhibit an increased susceptibility to activation of a Fas-triggered cell death pathway that is unique to motor neurons and 1 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000978468419997679<>ScoreDetail__11920|FAS|0.000978468419997679__3594|FASN|0.000566946990456392__ 0 0 0 0 0 113097 16624536 146898 14535 7873 NOS2A NOS NOS 35 2.7 neurons and which is dependent on transcriptional upregulation of neuronal NOS 36 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.00055378292828664<>ScoreDetail__7873|NOS2A|0.00055378292828664__7872|NOS1|0.000481082285414272__ 0 0 0 0 0 113098 16624536 146899 7333 11920 FAS FAS Fas 15 0.6 explanation for the sensitivity of motor neurons in particular to Fas ligand and NO-triggered cell death mediated at least in part 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000978468419997679<>ScoreDetail__11920|FAS|0.000978468419997679__3594|FASN|0.000566946990456392__ 0 0 0 0 0 113099 16624536 146902 5010 2434 CSF2 GM-CSF GM-CSF 28 2.2 the observation that granulocyte/macrophage granulocyte macrophage colony stimulating factor (GM-CSF) GM-CSF receptors are up-regulated on microglial cells adjacent to axotomized facial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113100 16624536 146903 5008 2432 CSF1 CSF1 CSF-1 3 1.2 Colony stimulating factor-1 (CSF-1) CSF-1 promotes the proliferation and differentiation of both monocytes 64 and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113101 16624536 146904 5008 2432 CSF1 CSF1 Csf1 5 1.2 In mice lacking this factor (Csf1 Csf1 op/op op op mutant mice only a limited microglial response 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113102 16624536 146906 5008 2432 CSF1 M-CSF M-CSF 23 1.2 observed in mice in which macrophage colony stimulating factor (M-CSF) M-CSF is absent 67 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113103 16624536 146908 10463 6018 IL6 IL-6 IL-6 0 1.6 IL-6 knockout mice not only fail to demonstrate the early microglial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113104 16624536 146908 10463 6018 IL6 IL-6 IL-6 30 1.6 reduced astrocytic response in keeping with a dual role of IL-6 in both mediating motor neuron/microglial neuron microglial and microglial/astrocytic microglial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113105 16624536 146909 20996 11179 SOD1 SOD1 SOD1 10 1.7 It is of interest that microglia derived from adult mutant SOD1 transgenic mice show decreased IL-6 production in response to LPS-stimulated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113106 16624536 146909 10463 6018 IL6 IL-6 IL-6 15 1.6 microglia derived from adult mutant SOD1 transgenic mice show decreased IL-6 production in response to LPS-stimulated activation compared to controls 37 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113107 16624536 146909 10676 6121 IRF6 LPS LPS-stimulated 20 0.6 SOD1 transgenic mice show decreased IL-6 production in response to LPS-stimulated activation compared to controls 37 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 113108 16624536 146911 5184 10647 CX3CL1 fractalkine fractalkine 2 1.3 The chemokine fractalkine has been identified as a chemoattractant in signaling the microglial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113109 16624536 146912 5184 10647 CX3CL1 fractalkine fractalkine 1 1.3 The fractalkine receptor CX3CR1 is expressed on both microglia and neurons 72 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113110 16624536 146912 5185 2558 CX3CR1 CX3CR1 CX3CR1 3 0.3 The fractalkine receptor CX3CR1 is expressed on both microglia and neurons 72 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113111 16624536 146914 5184 10647 CX3CL1 fractalkine fractalkine 12 1.3 to a role in the migration and proliferation of microglia fractalkine may also function as a microglial activator as receptor expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113112 16624536 146915 5184 10647 CX3CL1 fractalkine fractalkine 9 1.3 activation of the phosphatidylinositol-3 kinase/protein kinase protein kinase B pathway fractalkine will inhibit Fas ligand-induced microglial apoptosis through down-regulation of the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113113 16624536 146915 7333 11920 FAS FAS Fas 12 0.6 phosphatidylinositol-3 kinase/protein kinase protein kinase B pathway fractalkine will inhibit Fas ligand-induced microglial apoptosis through down-regulation of the pro-apoptotic function of 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000978468419997679<>ScoreDetail__11920|FAS|0.000978468419997679__3594|FASN|0.000566946990456392__ 0 0 0 0 0 113114 16624536 146915 1494 936 BAD BAD BAD 23 0.3 ligand-induced microglial apoptosis through down-regulation of the pro-apoptotic function of BAD and up-regulation of the anti-apoptotic activity of Bcl XL 71 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113115 16624536 146916 5184 10647 CX3CL1 fractalkine fractalkine 4 1.3 A similar effect of fractalkine upon hippocampal neurons exposed to the HIV envelop protein gp120 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113116 16624536 146916 543 391 AKT1 AKT Akt 26 0.6 been observed and attributed to activation of the protein kinase Akt and the nuclear translocation of NF-_amp_#x3ba B 72 and 75 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113117 16624536 146917 5184 10647 CX3CL1 fractalkine fractalkine 5 1.3 In murine cell culture experiments fractalkine suppressed the production of nitric oxide (NO), NO IL-6 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113118 16624536 146917 10463 6018 IL6 IL-6 IL-6 13 1.6 experiments fractalkine suppressed the production of nitric oxide (NO), NO IL-6 and TNF-by activated microglia and suppressed neuronal cell death induced 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113119 16624536 146917 10676 6121 IRF6 LPS LPS 29 0.6 and suppressed neuronal cell death induced by microglia activated with LPS and interferon-gamma (IFN-_amp_#x3b3;), IFN-_amp_#x3b3 in a dose-dependent manner 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 113120 16624536 146917 9905 5438 IFNG IFN IFN-G 32 0.6 death induced by microglia activated with LPS and interferon-gamma (IFN-_amp_#x3b3;), IFN-_amp_#x3b3 in a dose-dependent manner 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000669845890365346<>ScoreDetail__5438|IFNG|0.000523713639255262__5417|IFNA1|0.000669845890365346__ 0 0 0 0 0 113121 16624536 146918 5184 10647 CX3CL1 fractalkine fractalkine 1 1.3 Thus fractalkine might function as an intrinsic inhibitor against activated microglial-induced neurotoxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113122 16624536 146918 20996 11179 SOD1 ALS ALS 24 1.7 may therefore represent a viable target for pharmacological manipulation in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113123 16624536 146919 10437 5992 IL1B IL-1 IL-1 14 1.3 neuron interactions include a number of pro-inflammatory cytokines (e.g., e.g. IL-1 IL-6 and TNF- 77 78 and 79 and neurotrophic factors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113124 16624536 146919 10463 6018 IL6 IL-6 IL-6 15 1.6 interactions include a number of pro-inflammatory cytokines (e.g., e.g. IL-1 IL-6 and TNF- 77 78 and 79 and neurotrophic factors (e.g., 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113125 16624536 146919 22551 11892 TNF TNF TNF- 17 0.3 a number of pro-inflammatory cytokines (e.g., e.g. IL-1 IL-6 and TNF- 77 78 and 79 and neurotrophic factors (e.g., e.g. plasminogen 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113126 16624536 146919 14766 8053 NUDT6 bFGF bFGF 30 1.0 78 and 79 and neurotrophic factors (e.g., e.g. plasminogen TGF-_amp_#x3b2 bFGF BDNF NGF NT-3 and NT-4 80 81 and 82 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113127 16624536 146919 1624 1033 BDNF BDNF BDNF 31 0.3 and 79 and neurotrophic factors (e.g., e.g. plasminogen TGF-_amp_#x3b2 bFGF BDNF NGF NT-3 and NT-4 80 81 and 82 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113128 16624536 146919 14373 7808 NGF NGF NGF 32 1.2 79 and neurotrophic factors (e.g., e.g. plasminogen TGF-_amp_#x3b2 bFGF BDNF NGF NT-3 and NT-4 80 81 and 82 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113129 16624536 146919 14710 8020 NT3 NT3 NT-3 33 0.3 and neurotrophic factors (e.g., e.g. plasminogen TGF-_amp_#x3b2 bFGF BDNF NGF NT-3 and NT-4 80 81 and 82 6 JUMiner_v2.2 1 0 0 2 8023 TotalCon:3<>8020|NT3|4877|Complete__11186|SORT1|6272|Complete__8023|NTF3|4908|Complete__<>AvaiableGeneRif=3<>BEST:8023|NTF3|0.000685323926977153<>ScoreDetail__8023|NTF3|0.000685323926977153__11186|SORT1|0.000423744633190218__8020|NT3|0.00011879104654912__ 0 0 0 0 0 113130 16624536 146919 14728 8024 NTF4 NT4 NT-4 35 0.0 factors (e.g., e.g. plasminogen TGF-_amp_#x3b2 bFGF BDNF NGF NT-3 and NT-4 80 81 and 82 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113131 16624536 146920 10437 5992 IL1B IL-1 IL-1 0 1.3 IL-1 and TNF-have similar biological properties in that at higher concentrations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113132 16624536 146920 10676 6121 IRF6 LPS LPS 18 0.6 that at higher concentrations both mimic the cytotoxic effects of LPS 83 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 113133 16624536 146921 10437 5992 IL1B IL-1 IL-1 0 1.3 IL-1 mediates a general inflammatory response that recruits the further secretion 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113134 16624536 146921 10463 6018 IL6 IL-6 IL-6 15 1.6 that recruits the further secretion of pro-inflammatory cytokines (e.g., e.g. IL-6 IL-8 colony stimulating factors (CSFs), CSFs IFN- _amp_#x3b2 and can 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113135 16624536 146921 10470 6025 IL8 IL-8 IL-8 16 1.3 recruits the further secretion of pro-inflammatory cytokines (e.g., e.g. IL-6 IL-8 colony stimulating factors (CSFs), CSFs IFN- _amp_#x3b2 and can also 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113136 16624536 146921 11629 6493 LAMC2 CSF CSFs 20 0.3 pro-inflammatory cytokines (e.g., e.g. IL-6 IL-8 colony stimulating factors (CSFs), CSFs IFN- _amp_#x3b2 and can also have a trophic effect 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113137 16624536 146921 9905 5438 IFNG IFN IFN- 21 0.6 cytokines (e.g., e.g. IL-6 IL-8 colony stimulating factors (CSFs), CSFs IFN- _amp_#x3b2 and can also have a trophic effect 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000669845890365346<>ScoreDetail__5438|IFNG|0.000523713639255262__5417|IFNA1|0.000669845890365346__ 0 0 0 0 0 113138 16624536 146922 10437 5992 IL1B IL-1 IL-1 5 1.3 The use of a recombinant IL-1 receptor antagonist (r-Hu-met r-Hu-met Il-1ra significantly reduces the volume of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113139 16624536 146922 10444 5993 IL1R1 IL1RA Il-1ra 9 0.3 The use of a recombinant IL-1 receptor antagonist (r-Hu-met r-Hu-met Il-1ra significantly reduces the volume of damage following brain injury 84 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000312927432795913<>ScoreDetail__5993|IL1R1|0.000258636180453909__6000|IL1RN|0.000312927432795913__ 0 0 0 0 0 113140 16624536 146923 14373 7808 NGF NGF NGF 24 1.2 significant suppression of the extent of both microglial proliferation and NGF up-regulation is observed 85 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113141 16624536 146924 10437 5992 IL1B IL-1 IL-1 1 1.3 When IL-1 is added to mixed astrocytic/neuronal astrocytic neuronal cultures a 5- 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113142 16624536 146926 22561 11916 TNFRSF1A TNFR1 TNFR1 4 1.8 When signaling through the TNFR1 TNFR1 recruits a TNF receptor associated death domain (TRADD) TRADD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113143 16624536 146926 22561 11916 TNFRSF1A TNFR1 TNFR1 5 1.8 When signaling through the TNFR1 TNFR1 recruits a TNF receptor associated death domain (TRADD) TRADD that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113144 16624536 146926 22551 11892 TNF TNF TNF 8 0.3 When signaling through the TNFR1 TNFR1 recruits a TNF receptor associated death domain (TRADD) TRADD that can then interact 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113145 16624536 146926 22735 12030 TRADD TRADD TRADD 13 0.6 TNFR1 TNFR1 recruits a TNF receptor associated death domain (TRADD) TRADD that can then interact with the Fas-associated death domain to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113146 16624536 146926 7333 11920 FAS FAS Fas-associated 20 0.6 death domain (TRADD) TRADD that can then interact with the Fas-associated death domain to activate caspase 8 leading to downstream activation 1 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000978468419997679<>ScoreDetail__11920|FAS|0.000978468419997679__3594|FASN|0.000566946990456392__ 0 0 0 0 0 113147 16624536 146927 22561 11916 TNFRSF1A TNFR1 TNFR1 0 1.8 TNFR1 and TRADD activation can also lead to NF_amp_#x3ba B dependent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113148 16624536 146927 22735 12030 TRADD TRADD TRADD 2 0.6 TNFR1 and TRADD activation can also lead to NF_amp_#x3ba B dependent reporter gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113149 16624536 146927 9791 5329 IAPP IAP IAP 32 0.3 including survivin inhibitor of apoptosis protein-1 (IAP1), IAP1 IAP2 X-chromosome-linked IAP Bcl-2 Bcl-XL Bfl-1/A1, Bfl-1 A1 and FLIP 88 1 JUMiner_v2.2 1 0 0 2 437 TotalCon:4<>1682|CD47|961|Complete__5329|IAPP|3375|Complete__28880|MAGT1|84061|Complete__437|ALPI|248|Complete__<>AvaiableGeneRif=4<>BEST:437|ALPI|0.000646751253434098<>ScoreDetail__437|ALPI|0.000646751253434098__1682|CD47|0.000564122622732042__5329|IAPP|0.000462795022999689__28880|MAGT1|0.000633060359870466__ 0 0 0 0 0 113150 16624536 146927 1576 990 BCL2 Bcl-2 Bcl-2 33 1.0 survivin inhibitor of apoptosis protein-1 (IAP1), IAP1 IAP2 X-chromosome-linked IAP Bcl-2 Bcl-XL Bfl-1/A1, Bfl-1 A1 and FLIP 88 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113151 16624536 146927 4255 1876 CFLAR FLIP FLIP 39 1.0 IAP1 IAP2 X-chromosome-linked IAP Bcl-2 Bcl-XL Bfl-1/A1, Bfl-1 A1 and FLIP 88 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113152 16624536 146927 1577 991 BCL2A1 BFL1 Bfl-1 37 0.1 apoptosis protein-1 (IAP1), IAP1 IAP2 X-chromosome-linked IAP Bcl-2 Bcl-XL Bfl-1/A1, Bfl-1 A1 and FLIP 88 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113153 16624536 146928 22551 11892 TNF TNF TNF- 3 0.3 The interaction of TNF- or TNF-_amp_#x3b2 with TNFR2 leads to the activation of NF-_amp_#x3ba 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113154 16624536 146928 12108 6709 LTA TNF TNF-B 5 0.3 The interaction of TNF- or TNF-_amp_#x3b2 with TNFR2 leads to the activation of NF-_amp_#x3ba B and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113155 16624536 146928 22562 11917 TNFRSF1B TNFR2 TNFR2 7 1.8 The interaction of TNF- or TNF-_amp_#x3b2 with TNFR2 leads to the activation of NF-_amp_#x3ba B and the transcription 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113156 16624536 146929 22562 11917 TNFRSF1B TNFR2 TNFR2 6 1.8 Of interest knock out mice lacking TNFR2 show a failure to limit the immune response in experimental 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113157 16624536 146929 22551 11892 TNF TNF TNF 24 0.3 response in experimental autoimmune encephalitis and the use of p74 TNF receptor (TNFR2) TNFR2 antisense oligonucleotides will increase the extent of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113158 16624536 146929 22562 11917 TNFRSF1B TNFR2 TNFR2 26 1.8 autoimmune encephalitis and the use of p74 TNF receptor (TNFR2) TNFR2 antisense oligonucleotides will increase the extent of a hypoxic injury 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113159 16624536 146929 21482 16462 STRBP p74 p74 23 0.2 immune response in experimental autoimmune encephalitis and the use of p74 TNF receptor (TNFR2) TNFR2 antisense oligonucleotides will increase the extent 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113160 16624536 146930 22561 11916 TNFRSF1A TNF-R TNF-receptor 18 1.8 of brain injury is increased in transgenic mice lacking the TNF-receptor 91 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113161 16624536 146931 22551 11892 TNF TNF TNF-dependant 14 0.3 (an an NO-donor -induced neuronal apoptosis in vitro through a TNF-dependant mechanism whereas IL-3 IL-6 bFGF and M-CSF are ineffective in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113162 16624536 146931 10456 6011 IL3 IL-3 IL-3 18 1.6 -induced neuronal apoptosis in vitro through a TNF-dependant mechanism whereas IL-3 IL-6 bFGF and M-CSF are ineffective in the same experimental 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113163 16624536 146931 10463 6018 IL6 IL-6 IL-6 19 1.6 neuronal apoptosis in vitro through a TNF-dependant mechanism whereas IL-3 IL-6 bFGF and M-CSF are ineffective in the same experimental paradigm 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113164 16624536 146931 14766 8053 NUDT6 bFGF bFGF 20 1.0 apoptosis in vitro through a TNF-dependant mechanism whereas IL-3 IL-6 bFGF and M-CSF are ineffective in the same experimental paradigm 92 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113165 16624536 146931 5008 2432 CSF1 M-CSF M-CSF 22 1.2 vitro through a TNF-dependant mechanism whereas IL-3 IL-6 bFGF and M-CSF are ineffective in the same experimental paradigm 92 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113166 16624536 146936 20996 11179 SOD1 ALS ALS 1 1.7 In ALS neuronal function is compromised 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113167 16624536 146944 10676 6121 IRF6 LPS LPS-activated 11 0.6 it is an incorrect assumption to extrapolate the behaviour of LPS-activated microglia to that of microglia neighbouring degenerating motor neurons in 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 113168 16624536 146949 20996 11179 SOD1 ALS ALS 11 1.7 concept is reviewed in the discussion of adaptive immunity in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113169 16624536 146951 20996 11179 SOD1 ALS ALS 5 1.7 Adaptive and acquired immunity in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113170 16624536 146954 22088 15934 TH1L TH1 Th1 14 0.0 present antigens to a distinct subset of helper T-cells (Th1 Th1 cells capable of producing additional cytokines in order to amplify 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113171 16624536 146955 20996 11179 SOD1 ALS ALS 9 1.7 A study investigating systemic immune system changes in sporadic ALS revealed that increased levels of circulating monocytes and macrophages were 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113172 16624536 146956 3758 10618 CCL2 MCP-1 MCP-1 6 2.3 Increased levels of monocyte chemoattractant protein-1 (MCP-1) MCP-1 are seen in the cerebrospinal fluid (CSF) CSF from ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113173 16624536 146956 11629 6493 LAMC2 CSF CSF 13 0.3 protein-1 (MCP-1) MCP-1 are seen in the cerebrospinal fluid (CSF) CSF from ALS patients 98 and 99 13 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 113174 16624536 146956 20996 11179 SOD1 ALS ALS 15 1.7 MCP-1 are seen in the cerebrospinal fluid (CSF) CSF from ALS patients 98 and 99 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113175 16624536 146958 10437 5992 IL1B IL-1 IL-1 12 1.3 present antigen to Th1 cells which can in turn produce IL-1 IFN-_amp_#x3b3 TNF-_amp_#x3b2 and further activate macrophages 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113176 16624536 146958 9905 5438 IFNG IFN IFN-G 13 0.6 antigen to Th1 cells which can in turn produce IL-1 IFN-_amp_#x3b3 TNF-_amp_#x3b2 and further activate macrophages 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000669845890365346<>ScoreDetail__5438|IFNG|0.000523713639255262__5417|IFNA1|0.000669845890365346__ 0 0 0 0 0 113177 16624536 146958 12108 6709 LTA TNF TNF-B 14 0.3 to Th1 cells which can in turn produce IL-1 IFN-_amp_#x3b3 TNF-_amp_#x3b2 and further activate macrophages 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113178 16624536 146958 22088 15934 TH1L TH1 Th1 5 0.0 These cells present antigen to Th1 cells which can in turn produce IL-1 IFN-_amp_#x3b3 TNF-_amp_#x3b2 and 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113179 16624536 146960 20996 11179 SOD1 ALS ALS 27 1.7 to disease end stage time points in mouse models of ALS 34 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113180 16624536 146960 22088 15934 TH1L TH1 Th1 13 0.0 of cells mediating adaptive immunity in the CNS such as Th1 infiltrates is limited to disease end stage time points in 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113181 16624536 146961 20996 11179 SOD1 SOD1 SOD1 11 1.7 interest driving the adaptive immune response is protective against mutant SOD1 induced neurodegeneration 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113182 16624536 146962 20996 11179 SOD1 SOD1 SOD1 2 1.7 Vaccination of SOD1 G93A mice with Copaxone (copolymer-1) copolymer-1 led to an increase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113183 16624536 146963 22088 15934 TH1L TH1 Th1 10 0.0 This efficacy is thought to result from the sensitization of Th1 cells to self-antigens 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113184 16624536 146964 22088 15934 TH1L TH1 Th1 7 0.0 This theoretically leads to an increase in Th1 migration to injured sites activation and production of cytokines and 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113185 16624536 146965 926 620 APP amyloid amyloid 2 1.0 Protection against _amp_#x3b2 -amyloid and glutamate excitotoxicity has been achieved through control of microglial 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 113186 16624536 146965 3865 1678 CD4 CD4 CD4 20 0.3 control of microglial phenotype via the presence or absence of CD4 CD25 helper T cells 96 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113187 16624536 146965 10701 6130 ISG20 CD25 CD25 20 1.6 of microglial phenotype via the presence or absence of CD4 CD25 helper T cells 96 1 JUMiner_v2.2 1 0 0 2 6008 TotalCon:2<>6008|IL2RA|3559|Complete__6130|ISG20|3669|Complete__<>AvaiableGeneRif=2<>BEST:6008|IL2RA|0.000724769060934277<>ScoreDetail__6130|ISG20|0.000261340302408064__6008|IL2RA|0.000724769060934277__ 0 0 0 0 0 113188 16624536 146966 9905 5438 IFNG IFN IFN-G 21 0.6 with CNS-specific self-antigens may arise from stimulation of microglia with IFN-_amp_#x3b3 which is produced by reactive helper T cells 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000669845890365346<>ScoreDetail__5438|IFNG|0.000523713639255262__5417|IFNA1|0.000669845890365346__ 0 0 0 0 0 113189 16624536 146967 17610 9605 PTGS2 COX-2 COX-2 21 1.5 as well as decreased mRNA expression of inflammatory products including COX-2 iNOS and I_amp_#x3ba B (an an inhibitor of NF-_amp_#x3ba B 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113190 16624536 146967 14535 7873 NOS2A iNOS iNOS 22 2.7 well as decreased mRNA expression of inflammatory products including COX-2 iNOS and I_amp_#x3ba B (an an inhibitor of NF-_amp_#x3ba B by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113191 16624536 146967 10676 6121 IRF6 LPS LPS-treated 33 0.6 (an an inhibitor of NF-_amp_#x3ba B by microglia compared to LPS-treated microglia 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 113192 16624536 146968 9905 5438 IFNG IFN IFN-G 2 0.6 In addition IFN-_amp_#x3b3 -stimulated microglia had greater antigen-presenting capability and were therefore able 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000669845890365346<>ScoreDetail__5438|IFNG|0.000523713639255262__5417|IFNA1|0.000669845890365346__ 0 0 0 0 0 113193 16624536 146968 22088 15934 TH1L TH1 Th1 16 0.0 antigen-presenting capability and were therefore able to more efficiently recruit Th1 cells and increase glutamate clearance 95 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113194 16624536 146972 20996 11179 SOD1 ALS ALS 17 1.7 the role of IgG in inducing altered calcium permeability in ALS motor neurons IgG isolated from ALS patient serum injected intraperitoneally 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113195 16624536 146972 20996 11179 SOD1 ALS ALS 23 1.7 altered calcium permeability in ALS motor neurons IgG isolated from ALS patient serum injected intraperitoneally into mice has been shown to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113196 16624536 146973 20996 11179 SOD1 ALS ALS 11 1.7 in vivo studies have demonstrated the ability of passively transferred ALS IgG to cause recruitment of activated microglia 104 and motor 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113197 16624536 146974 20996 11179 SOD1 ALS ALS 16 1.7 mixed primary spinal cord cultures that IgG from patients with ALS induces apoptosis via the caspase-3 pathway selectively in motor neurons 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113198 16624536 146975 20996 11179 SOD1 ALS ALS 6 1.7 One experiment demonstrated the ability of ALS IgG to shift the activation curve of calcium current indicating 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113199 16624536 146976 20996 11179 SOD1 ALS ALS 20 1.7 demonstrate such effects in rat cerebral synaptosomes thus concluding that ALS IgG is ineffective in enhancing presynaptic calcium influx 109 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113200 16624536 146980 20996 11179 SOD1 ALS ALS 20 1.7 also become reactive in areas of motor neuron degeneration in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113201 16624536 146982 20996 11179 SOD1 ALS ALS 11 1.7 function as executors of glutamate clearance may be compromised in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113202 16624536 146983 20996 11179 SOD1 SOD1 SOD1 5 1.7 Astrocytes isolated from a mutant SOD1 transgenic rat show a 3-fold higher expression of mGluR5 over 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113203 16624536 146983 8797 4579 GRIK1 GLUR5 mGluR5 14 0.3 mutant SOD1 transgenic rat show a 3-fold higher expression of mGluR5 over controls activation of which fails to lead to increased 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113204 16624536 146984 20996 11179 SOD1 ALS ALS 7 1.7 Although the evidence is controversial astrocytes in ALS have been observed to have decreased expression of the glutamate 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113205 16624536 146984 20017 10940 SLC1A2 EAAT2 EAAT2 19 1.0 been observed to have decreased expression of the glutamate transporter EAAT2 potentially leading to decreased glutamate transport and subsequent increases in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113206 16624536 146985 20017 10940 SLC1A2 EAAT2 EAAT2 11 1.0 this decrease in expression resulting from alternately spliced variants of EAAT2 has been demonstrated in normal controls in addition to ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113207 16624536 146985 20996 11179 SOD1 ALS ALS 21 1.7 EAAT2 has been demonstrated in normal controls in addition to ALS patients 112 and 113 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113208 16624536 146986 3758 10618 CCL2 MCP-1 MCP-1 3 2.3 Monocyte chemoattractant protein-1 (MCP-1) MCP-1 is critical for migration of monoctyes to areas of injury 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113209 16624536 146987 20996 11179 SOD1 ALS ALS 10 1.7 As discussed in relation to adaptive and acquired immunity in ALS MCP-1 concentrations are significantly increased in both serum and cerebrospinal 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113210 16624536 146987 3758 10618 CCL2 MCP-1 MCP-1 11 2.3 discussed in relation to adaptive and acquired immunity in ALS MCP-1 concentrations are significantly increased in both serum and cerebrospinal fluid 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113211 16624536 146987 11629 6493 LAMC2 CSF CSF 22 0.3 are significantly increased in both serum and cerebrospinal fluid (CSF) CSF from ALS patients 13 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 113212 16624536 146987 20996 11179 SOD1 ALS ALS 24 1.7 increased in both serum and cerebrospinal fluid (CSF) CSF from ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113213 16624536 146988 3758 10618 CCL2 MCP-1 MCP-1 0 2.3 MCP-1 immunoreactivity is highest in astrocytes in ALS spinal cord suggesting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113214 16624536 146988 20996 11179 SOD1 ALS ALS 7 1.7 MCP-1 immunoreactivity is highest in astrocytes in ALS spinal cord suggesting that astrocytes have an important role in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113215 16624536 146988 20996 11179 SOD1 ALS ALS 25 1.7 important role in mediating the inflammatory response to injury in ALS 98 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113216 16624536 146990 14535 7873 NOS2A iNOS iNOS 8 2.7 Like microglia reactive astrocytes express inflammatory markers including iNOS and COX-2 114 and can produce proinflammatory mediators including prostaglandins 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113217 16624536 146990 17610 9605 PTGS2 COX-2 COX-2 10 1.5 Like microglia reactive astrocytes express inflammatory markers including iNOS and COX-2 114 and can produce proinflammatory mediators including prostaglandins 115 IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113218 16624536 146990 10463 6018 IL6 IL-6 IL-6 21 1.6 COX-2 114 and can produce proinflammatory mediators including prostaglandins 115 IL-6 116 and TNF- 114 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113219 16624536 146990 22551 11892 TNF TNF TNF- 24 0.3 can produce proinflammatory mediators including prostaglandins 115 IL-6 116 and TNF- 114 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113220 16624536 146992 7521 3665 FGF1 FGF1 FGF-1 3 1.2 Fibroblast growth factor-1 (FGF-1) FGF-1 released from motor neurons in response to injury or oxidative 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113221 16624536 146992 7548 3688 FGFR1 FGFR1 FGFR1 21 1.2 or oxidative stress leads to accumulation of FGF receptor-1 (FGFR1) FGFR1 in astrocytic nuclei and stimulates nerve growth factor (NGF) NGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113222 16624536 146992 14373 7808 NGF NGF NGF 30 1.2 FGFR1 in astrocytic nuclei and stimulates nerve growth factor (NGF) NGF expression and secretion by astrocytes 117 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113223 16624536 146993 14373 7808 NGF NGF NGF 1 1.2 This NGF production has been previously shown to induce motor neuron apoptosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113224 16624536 146993 22562 11917 TNFRSF1B p75 p75-dependent 14 1.8 been previously shown to induce motor neuron apoptosis via a p75-dependent mechanism 118 and 119 11 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000658415490562952<>ScoreDetail__9527|PSIP1|0.000402796810900032__2557|CUX1|0.000516002919969465__10876|SIGLEC7|0.000658415490562952__11917|TNFRSF1B|0.000437053748054442__ 0 0 0 0 0 113225 16624536 146994 7333 11920 FAS FAS Fas 0 0.6 Fas ligand and TNF-produced by reactive astrocytes can also activate death 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000978468419997679<>ScoreDetail__11920|FAS|0.000978468419997679__3594|FASN|0.000566946990456392__ 0 0 0 0 0 113226 16624536 146994 22551 11892 TNF TNF TNF-produced 3 0.3 Fas ligand and TNF-produced by reactive astrocytes can also activate death receptors in injured 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113227 16624536 146995 20996 11179 SOD1 ALS ALS 8 1.7 Returning to the work of Raoul et al. ALS motor neurons are particularly susceptible to Fas signaling and the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113228 16624536 146995 7333 11920 FAS FAS Fas 15 0.6 Raoul et al. ALS motor neurons are particularly susceptible to Fas signaling and the apoptotic pathway implicated is motor neuron-specific 36 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.000978468419997679<>ScoreDetail__11920|FAS|0.000978468419997679__3594|FASN|0.000566946990456392__ 0 0 0 0 0 113229 16624536 146999 20996 11179 SOD1 ALS ALS 3 1.7 Anti-inflammatory treatment of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113230 16624536 147000 20996 11179 SOD1 ALS ALS 10 1.7 The identification of microglial activation and proliferation as hallmarks of ALS in vivo and as contributors to motor neuron death in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113231 16624536 147001 20996 11179 SOD1 SOD1 SOD1 42 1.7 of motor dysfunction by roughly 9_amp_#x2013 20% in various mutant SOD1 transgenic mice and extends survival by 13_amp_#x2013 25% (in in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113232 16624536 147004 14535 7873 NOS2A iNOS iNOS 21 2.7 the level of the microglia in which the up-regulation of iNOS is inhibited and at the target cell where the release 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113233 16624536 147006 20996 11179 SOD1 ALS ALS 10 1.7 led to phase I/II I II studies of minocycline in ALS patients 134 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113234 16624536 147010 17610 9605 PTGS2 COX-2 COX-2 7 1.5 Celecoxib (Celebrex) Celebrex and rofecoxib are inhibitors of COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113235 16624536 147011 17610 9605 PTGS2 COX-2 COX-2 3 1.5 Treatment with these COX-2 inhibitors combined with creatine increased survival by up to 30% 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113236 16624536 147011 20996 11179 SOD1 SOD1 SOD1 15 1.7 combined with creatine increased survival by up to 30% in SOD1 mutant mice 139 140 and 141 while treatment with a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113237 16624536 147011 17610 9605 PTGS2 COX COX 28 0.6 mice 139 140 and 141 while treatment with a non-specific COX inhibitor (sulindac) sulindac extended survival by roughly 10% 142 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 113238 16624536 147012 17610 9605 PTGS2 COX COX 11 0.6 should be noted however that to date none of the COX inhibitors tested have shown efficacy in human ALS patients 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 113239 16624536 147012 20996 11179 SOD1 ALS ALS 19 1.7 of the COX inhibitors tested have shown efficacy in human ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113240 16624536 147017 20996 11179 SOD1 ALS ALS 17 1.7 for microglia and their inflammatory products in the pathogenesis of ALS the most significant pieces of information remain elusive 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113241 16624536 147019 20996 11179 SOD1 ALS ALS 18 1.7 motor neurons and take on a protective role or is ALS a disease with auto-immune characteristics 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113242 16624536 147021 20996 11179 SOD1 SOD1 SOD1 7 1.7 This is supported by evidence that mutant SOD1 secreted from neurons can activate microglia and lead to neuronal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113243 16624536 147022 20996 11179 SOD1 ALS ALS 6 1.7 Other studies suggest however that in ALS microglia can have cytotoxic potential regardless of the health status 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113244 16624536 147024 20996 11179 SOD1 SOD1 SOD1 7 1.7 The results of minocycline treatment of mutant SOD1 mice suggest that microglial activation is concomitant with and contributes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113245 16624536 147026 20996 11179 SOD1 ALS ALS 3 1.7 As discussed previously ALS is clearly a multi-factorial disease in which complex neuronal_amp_#x2013 glial 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113246 16624536 147028 20996 11179 SOD1 ALS ALS 12 1.7 also important that the relationships between various pathological features of ALS intrinsic to motor neurons themselves and the glial inflammatory response 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113247 16624536 147029 20996 11179 SOD1 SOD1 SOD1 2 1.7 Although mutant SOD1 models allow for validation of potential treatments they do not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 113248 16624536 147031 20996 11179 SOD1 ALS ALS 10 1.7 Immunity is therefore a process that is potentially altered in ALS and as such is an intriguing candidate for therapeutic intervention 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113249 16624536 147032 20996 11179 SOD1 ALS ALS 6 1.7 This is not to say that ALS is a disease of cells of the macrophage lineage 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113250 16624536 147033 20996 11179 SOD1 ALS ALS 5 1.7 Rather the evidence suggests that ALS is a disease in which inflammation remains a theoretically beneficial 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113251 16624536 147034 20996 11179 SOD1 ALS ALS 21 1.7 creates controversy as to their role in the pathogenesis of ALS but also offers therapeutic potential as a useful tool in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113252 16624536 147034 20996 11179 SOD1 ALS ALS 41 1.7 in the modulation of factors influencing motor neuron death in ALS such as release of inflammatory mediators with pro-apoptotic effects and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 113253 16624536 147035 20996 11179 SOD1 ALS ALS 8 1.7 Perhaps inflammation is a key determinant of the ALS disease process but its elimination as a therapeutic objective may 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000788452378603699<>ScoreDetail__5468|IGFALS|0.000436151439801075__11179|SOD1|0.000788452378603699__ 0 0 0 0 0 114306 16637591 148922 19309 10500 S100B S100B S100B 0 3.4 S100B astrocyte specific protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 114307 16637591 148923 19309 10500 S100B S100B S100B 1 3.4 The S100B is a Ca2 binding proteins of EF-hand type and is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 114308 16637591 148925 19309 10500 S100B S100B S100B 5 3.4 Recent studies suggest that released S100B exerts paracrine and autocrine effects on neurons and glia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 114309 16637591 148926 19309 10500 S100B S100B S100B 6 3.4 On the other hand elevations of S100B levels in blood or cerebrospinal fluid have been observed in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 114310 16637591 148927 19309 10500 S100B S100B S100B 7 3.4 It has been documented that the excessive S100B promotes the expression of inducible nitric oxide synthase or pro-inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 114311 16637591 148928 19309 10500 S100B S100B S100B 19 3.4 stroke or Alzheimer's disease it is suggested that the excessive S100B produced by activated astrocytes precedes neurodegenerations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 114312 16637591 148929 19309 10500 S100B S100B S100B 9 3.4 Authors discussed the relationship between neurological disorders and the S100B 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115224 16647138 150263 17610 9605 PTGS2 COX COX 2 2.9 Thus cyclooxygenases (COX), COX lipoxygenases (LOX), LOX and epoxygenases (EPOX) EPOX metabolize AA to 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115225 16647138 150263 11934 6664 LOX LOX LOX 4 3.3 Thus cyclooxygenases (COX), COX lipoxygenases (LOX), LOX and epoxygenases (EPOX) EPOX metabolize AA to prostaglandins thromboxanes leukotrienes 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115226 16647138 150263 6701 3401 EPHX1 EPOX EPOX 7 2.9 Thus cyclooxygenases (COX), COX lipoxygenases (LOX), LOX and epoxygenases (EPOX) EPOX metabolize AA to prostaglandins thromboxanes leukotrienes and epoxyeicosatrienoic acid respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115227 16647138 150267 17610 9605 PTGS2 COX COX 2 2.9 In contrast COX and LOX metabolize DHA to resolvins docosatrienes and neuroprotectins 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115228 16647138 150267 11934 6664 LOX LOX LOX 4 3.3 In contrast COX and LOX metabolize DHA to resolvins docosatrienes and neuroprotectins 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115229 16647138 150270 17610 9605 PTGS2 COX COX 12 2.9 and non-neural tissues express several different isoforms of PLA 2 COX and LOX under normal or stimulated situations ( Kis et 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115230 16647138 150270 11934 6664 LOX LOX LOX 14 3.3 tissues express several different isoforms of PLA 2 COX and LOX under normal or stimulated situations ( Kis et al. 2003 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115231 16647138 150270 23681 19683 UHMK1 KIS Kis 21 0.6 2 COX and LOX under normal or stimulated situations ( Kis et al. 2003 Kis et al. 2004 Kolko et al. 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 115232 16647138 150270 23681 19683 UHMK1 KIS Kis 26 0.6 under normal or stimulated situations ( Kis et al. 2003 Kis et al. 2004 Kolko et al. 2005 Shaftel et al. 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 115233 16647138 150271 17610 9605 PTGS2 COX COX 7 2.9 How the isoforms of PLA 2 COX and LOX enzymes interact with each other remains to be 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115234 16647138 150271 11934 6664 LOX LOX LOX 9 3.3 How the isoforms of PLA 2 COX and LOX enzymes interact with each other remains to be elucidated 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115235 16647138 150273 17610 9605 PTGS2 COX COX 3 2.9 Eicosanoid synthesis through COX and LOX enzymes may involve different AA substrate pools and 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115236 16647138 150273 11934 6664 LOX LOX LOX 5 3.3 Eicosanoid synthesis through COX and LOX enzymes may involve different AA substrate pools and may be 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115237 16647138 150274 11001 28961 KIAA0101 PAF PAF 18 0.3 1-alkyl-2-lyso-sn -glycero-3-phosphocholine is the immediate precursor for platelet-activating factor (PAF), PAF a potent inflammatory mediator 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115238 16647138 150275 11001 28961 KIAA0101 PAF PAF 5 0.3 Besides inflammation in brain tissue PAF modulates transcription factors and gene expression and is involved in 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115239 16647138 150275 16745 9065 PLCG1 PLC PLC 23 0.6 and is involved in stimulation and modulation of PLA 2 PLC and PLD and COX activities 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115240 16647138 150275 17610 9605 PTGS2 COX COX 27 2.9 stimulation and modulation of PLA 2 PLC and PLD and COX activities 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115241 16647138 150276 17610 9605 PTGS2 COX COX 7 2.9 In addition to the abovementioned lipid mediators COX LOX and EPOX-catalyzed reactions also produce reactive oxygen species (ROS) 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115242 16647138 150276 11934 6664 LOX LOX LOX 8 3.3 In addition to the abovementioned lipid mediators COX LOX and EPOX-catalyzed reactions also produce reactive oxygen species (ROS) ROS 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115243 16647138 150276 6701 3401 EPHX1 EPOX EPOX-catalyzed 10 1.6 In addition to the abovementioned lipid mediators COX LOX and EPOX-catalyzed reactions also produce reactive oxygen species (ROS) ROS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115244 16647138 150276 18723 10261 ROS1 ROS ROS 17 0.0 LOX and EPOX-catalyzed reactions also produce reactive oxygen species (ROS) ROS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115245 16647138 150277 18723 10261 ROS1 ROS ROS 0 0.0 ROS include oxygen free radicals (superoxide superoxide radicals hydroxyl and alkoxyl 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115246 16647138 150278 18723 10261 ROS1 ROS ROS 3 0.0 At low levels ROS function as signaling intermediates in the regulation of fundamental cell 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115247 16647138 150279 18723 10261 ROS1 ROS ROS 3 0.0 At higher concentration ROS contribute to neural membrane damage when the balance between reducing 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115248 16647138 150280 18723 10261 ROS1 ROS ROS 5 0.0 The other biological targets of ROS may be membrane proteins unsaturated lipids and DNA ( Berlett 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115249 16647138 150281 18723 10261 ROS1 ROS ROS 3 0.0 The reaction between ROS and proteins or unsaturated lipids in the plasma membrane leads 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115250 16647138 150282 19891 29546 SH3YL1 Ray Ray 24 0.9 decreased activity of membrane-bound enzymes ion channels and receptors ( Ray et al. 1994 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115251 16647138 150288 17610 9605 PTGS2 COX COX 13 2.9 summarize studies on the multiplicity properties regulation and roles of COX LOX and EPOX in brain tissue 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115252 16647138 150288 11934 6664 LOX LOX LOX 14 3.3 studies on the multiplicity properties regulation and roles of COX LOX and EPOX in brain tissue 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115253 16647138 150288 6701 3401 EPHX1 EPOX EPOX 16 2.9 the multiplicity properties regulation and roles of COX LOX and EPOX in brain tissue 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115254 16647138 150289 17610 9605 PTGS2 COX COX 32 2.9 this discussion would initiate more studies on the importance of COX LOX EPOX and their lipid mediators in neurological disorders 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115255 16647138 150289 11934 6664 LOX LOX LOX 33 3.3 discussion would initiate more studies on the importance of COX LOX EPOX and their lipid mediators in neurological disorders 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115256 16647138 150289 6701 3401 EPHX1 EPOX EPOX 34 2.9 would initiate more studies on the importance of COX LOX EPOX and their lipid mediators in neurological disorders 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115257 16647138 150290 17610 9605 PTGS2 COX COX 3 2.9 The inhibition of COX LOX and EPOX activities may provide an attractive approach for 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115258 16647138 150290 11934 6664 LOX LOX LOX 4 3.3 The inhibition of COX LOX and EPOX activities may provide an attractive approach for designing 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115259 16647138 150290 6701 3401 EPHX1 EPOX EPOX 6 2.9 The inhibition of COX LOX and EPOX activities may provide an attractive approach for designing novel drugs 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115260 16647138 150311 17610 9605 PTGS2 COX COX 1 2.9 Cyclooxygenases (COX) COX 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115261 16647138 150313 16457 8891 PGD PGD PGD 7 0.3 Among the dilator prostanoids are the prostaglandins (PGD PGD 2 and PGE 2 and prostacyclin (PGI PGI 2 whereas 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115262 16647138 150313 8612 4458 GPI PGI PGI 15 0.6 prostaglandins (PGD PGD 2 and PGE 2 and prostacyclin (PGI PGI 2 whereas constrictor prostanoids include thromboxane (TXA TXA 2 and 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000317087492660012<>ScoreDetail__1044|BGN|0.000317087492660012__4458|GPI|0.000299625468164794__ 0 0 0 0 0 115263 16647138 150313 16459 8893 PGF PGF PGF 27 0.6 2 whereas constrictor prostanoids include thromboxane (TXA TXA 2 and PGF 2_amp_#x3b1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115264 16647138 150315 16459 8893 PGF PGF PGF 3 0.6 In human brain PGF 2_amp_#x3b1 is the most abundant prostanoid followed by PGE 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115265 16647138 150315 8612 4458 GPI PGI PGI 16 0.6 is the most abundant prostanoid followed by PGE 2 whereas PGI 2 is the principal prostanoid in human CSF ( Abdel-Halim 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000317087492660012<>ScoreDetail__1044|BGN|0.000317087492660012__4458|GPI|0.000299625468164794__ 0 0 0 0 0 115266 16647138 150315 11629 6493 LAMC2 CSF CSF 24 0.0 2 whereas PGI 2 is the principal prostanoid in human CSF ( Abdel-Halim et al. 1980b 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115267 16647138 150316 16457 8891 PGD PGD PGD 7 0.3 The predominant prostanoid in rodent brains is PGD 2 ( Abdel-Halim et al. 1980a 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115268 16647138 150322 16963 14121 POLR3K C11 C-11 9 0.6 Detailed mechanistic studies revealed a carbon-centered pentadienyl radical at C-11 and a carbon-centered radical at C-8 as the two radical 11 JUMiner_v2.2 1 0 0 2 14121 TotalCon:2<>387|AKR1C4|1109|Complete__14121|POLR3K|51728|Complete__<>AvaiableGeneRif=2<>BEST:14121|POLR3K|0.000485904395027141<>ScoreDetail__14121|POLR3K|0.000485904395027141__387|AKR1C4|0.00037080144612564__ 0 0 0 0 0 115269 16647138 150323 17610 9605 PTGS2 COX COX 38 2.9 PGG 2 to generate a radical intermediate that begins the COX reaction ( Jiang et al. 2004 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115270 16647138 150324 8612 4458 GPI PGI PGI 14 0.6 to several prostaglandins thromboxanes (TXA TXA 2 and prostacyclins (PGI PGI 2 ( Fig 2 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000317087492660012<>ScoreDetail__1044|BGN|0.000317087492660012__4458|GPI|0.000299625468164794__ 0 0 0 0 0 115271 16647138 150326 17610 9605 PTGS2 COX COX 3 2.9 Three forms of COX enzymes designated as COX-1 COX-2 and COX-3 occur in mammalian 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115272 16647138 150326 17609 9604 PTGS1 COX-1 COX-1 7 4.9 Three forms of COX enzymes designated as COX-1 COX-2 and COX-3 occur in mammalian tissues 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115273 16647138 150326 17610 9605 PTGS2 COX-2 COX-2 8 16.2 Three forms of COX enzymes designated as COX-1 COX-2 and COX-3 occur in mammalian tissues 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115274 16647138 150326 13733 7422 MT-CO3 COX3 COX3 8 0.6 Three forms of COX enzymes designated as COX-1 COX-2 and COX-3 occur in mammalian tissues 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115275 16647138 150326 13733 7422 MT-CO3 COX3 COX-3 10 4.6 Three forms of COX enzymes designated as COX-1 COX-2 and COX-3 occur in mammalian tissues 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115276 16647138 150327 17609 9604 PTGS1 COX-1 COX-1 0 4.9 COX-1 is a constitutively expressed in brain tissue and is responsible 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115277 16647138 150329 17610 9605 PTGS2 COX-2 COX-2 12 16.2 such as cytokines growth factors and bacterial endotoxin rapidly induce COX-2 which is normally undetectable in healthy tissues 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115278 16647138 150330 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 is constitutively expressed in the kidney stomach and brain ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115279 16647138 150331 17609 9604 PTGS1 COX-1 COX-1 0 4.9 COX-1 and COX-2 are homodimers 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115280 16647138 150331 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-1 and COX-2 are homodimers 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115281 16647138 150331 17610 9605 PTGS2 COX-2 COX-2 2 16.2 COX-1 and COX-2 are homodimers 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115282 16647138 150334 17609 9604 PTGS1 COX-1 COX-1 0 4.9 COX-1 contains Val at the 434 and 523 positions whereas COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115283 16647138 150334 17610 9605 PTGS2 COX-2 COX-2 10 16.2 COX-1 contains Val at the 434 and 523 positions whereas COX-2 has Ile at positions 434 and 523 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115284 16647138 150335 17610 9605 PTGS2 COX-2 COX-2 19 16.2 larger and more flexible substrate and inhibitor binding sites in COX-2 than in COX-1 ( Kurumbail et al. 1996 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115285 16647138 150335 17609 9604 PTGS1 COX-1 COX-1 22 4.9 flexible substrate and inhibitor binding sites in COX-2 than in COX-1 ( Kurumbail et al. 1996 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115286 16647138 150336 17609 9604 PTGS1 COX-1 COX-1 5 4.9 The amino acid sequences of COX-1 and COX-2 also differ from each other at the N- 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115287 16647138 150336 17610 9605 PTGS2 COX-2 COX-2 5 16.2 The amino acid sequences of COX-1 and COX-2 also differ from each other at the N- 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115288 16647138 150336 17610 9605 PTGS2 COX-2 COX-2 7 16.2 The amino acid sequences of COX-1 and COX-2 also differ from each other at the N- and C-termini 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115289 16647138 150337 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 lacks a 17 amino acid sequence at the N-terminus but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115290 16647138 150338 17610 9605 PTGS2 COX-2 COX-2 5 16.2 Thus the active site of COX-2 is larger and more accommodating than that of COX-1 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115291 16647138 150338 17609 9604 PTGS1 COX-1 COX-1 14 4.9 of COX-2 is larger and more accommodating than that of COX-1 and COX-1 displays negative allosterism at low concentrations of AA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115292 16647138 150338 17609 9604 PTGS1 COX-1 COX-1 14 4.9 of COX-2 is larger and more accommodating than that of COX-1 and COX-1 displays negative allosterism at low concentrations of AA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115293 16647138 150338 17609 9604 PTGS1 COX-1 COX-1 16 4.9 is larger and more accommodating than that of COX-1 and COX-1 displays negative allosterism at low concentrations of AA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115294 16647138 150339 17610 9605 PTGS2 COX-2 COX-2 10 16.2 This property may be responsible for greater eicosanoid production by COX-2 when the AA concentration is low ( Smith et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115295 16647138 150340 17609 9604 PTGS1 COX-1 COX-1 6 4.9 AA is the preferred substrate for COX-1 and COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115296 16647138 150340 17610 9605 PTGS2 COX-2 COX-2 6 16.2 AA is the preferred substrate for COX-1 and COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115297 16647138 150340 17610 9605 PTGS2 COX-2 COX-2 8 16.2 AA is the preferred substrate for COX-1 and COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115298 16647138 150342 17610 9605 PTGS2 COX COX 3 2.9 The action of COX enzymes on eicosapentaenoic acid generates the 3-series of prostaglandins and 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115299 16647138 150345 17610 9605 PTGS2 COX COX 3 2.9 All isoforms of COX enzymes have been cloned ( DeWitt and Smith 1988 and 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115300 16647138 150346 17610 9605 PTGS2 COX-2 COX-2 1 16.2 The COX-2 gene is 8.3 kb whereas the COX-1 gene is much 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115301 16647138 150346 17609 9604 PTGS1 COX-1 COX-1 8 4.9 The COX-2 gene is 8.3 kb whereas the COX-1 gene is much larger (22 22 kb ( Vane et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115302 16647138 150347 17609 9604 PTGS1 COX-1 COX-1 0 4.9 COX-1 mRNA is approximately 2.8 kb while COX-2 mRNA is approximately 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115303 16647138 150347 17610 9605 PTGS2 COX-2 COX-2 7 16.2 COX-1 mRNA is approximately 2.8 kb while COX-2 mRNA is approximately 4.0 kb 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115304 16647138 150348 17609 9604 PTGS1 COX-1 COX-1 7 4.9 Analysis of the 5_amp_#x2032 -flanking untranslated regions of COX-1 and COX-2 indicates that the COX-1 gene is associated with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115305 16647138 150348 17610 9605 PTGS2 COX-2 COX-2 7 16.2 Analysis of the 5_amp_#x2032 -flanking untranslated regions of COX-1 and COX-2 indicates that the COX-1 gene is associated with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115306 16647138 150348 17610 9605 PTGS2 COX-2 COX-2 9 16.2 Analysis of the 5_amp_#x2032 -flanking untranslated regions of COX-1 and COX-2 indicates that the COX-1 gene is associated with housekeeping activities 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115307 16647138 150348 17609 9604 PTGS1 COX-1 COX-1 13 4.9 -flanking untranslated regions of COX-1 and COX-2 indicates that the COX-1 gene is associated with housekeeping activities whereas the COX-2 gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115308 16647138 150348 17610 9605 PTGS2 COX-2 COX-2 22 16.2 the COX-1 gene is associated with housekeeping activities whereas the COX-2 gene is involved in response-related activities 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115309 16647138 150349 17610 9605 PTGS2 COX-2 COX-2 5 16.2 The 5_amp_#x2032 -flanking region of the COX-2 gene has a TATA box 30 base pairs upstream from 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115310 16647138 150349 17609 9604 PTGS1 COX-1 COX-1 32 4.9 Tazawa et al. 1994 whereas the same region in the COX-1 gene has no canonic TATA box ( Wu 1995 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115311 16647138 150350 17610 9605 PTGS2 COX-2 COX-2 1 16.2 The COX-2 gene also contains a number of putative regulatory sites including 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115312 16647138 150350 10463 6018 IL6 IL-6 IL-6 17 1.3 of putative regulatory sites including the cyclic AMP response element IL-6 response element AP-2 nuclear factor-_amp_#x3ba B (NF-_amp_#x3ba;B), NF-_amp_#x3ba B Sp-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115313 16647138 150350 22027 11742 TFAP2A AP-2 AP-2 20 1.6 sites including the cyclic AMP response element IL-6 response element AP-2 nuclear factor-_amp_#x3ba B (NF-_amp_#x3ba;B), NF-_amp_#x3ba B Sp-1 PEA-3 GATA-1 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115314 16647138 150350 5443 26780 DAND5 SP1 Sp-1 24 0.6 IL-6 response element AP-2 nuclear factor-_amp_#x3ba B (NF-_amp_#x3ba;B), NF-_amp_#x3ba B Sp-1 PEA-3 GATA-1 and glucocorticoid response element ( Wu 1995 11 JUMiner_v2.2 1 0 0 2 11205 TotalCon:3<>11205|SP1|6667|Complete__26780|DAND5|199699|No_GeneRif__9514|PSG1|5669|Complete__<>AvaiableGeneRif=2<>BEST:11205|SP1|0.000506004165608438<>ScoreDetail__9514|PSG1|0.000292956911762725__11205|SP1|0.000506004165608438__ 0 0 0 0 0 115315 16647138 150350 6818 3493 ETV4 PEA3 PEA-3 25 0.6 response element AP-2 nuclear factor-_amp_#x3ba B (NF-_amp_#x3ba;B), NF-_amp_#x3ba B Sp-1 PEA-3 GATA-1 and glucocorticoid response element ( Wu 1995 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115316 16647138 150350 8159 4170 GATA1 GATA1 GATA-1 26 0.6 element AP-2 nuclear factor-_amp_#x3ba B (NF-_amp_#x3ba;B), NF-_amp_#x3ba B Sp-1 PEA-3 GATA-1 and glucocorticoid response element ( Wu 1995 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115317 16647138 150351 10458 6014 IL4 IL-4 IL-4 8 1.3 Thus factors that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 can specifically inhibit COX-2 upregulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115318 16647138 150351 10480 5962 IL10 IL-10 IL-10 9 1.3 Thus factors that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 can specifically inhibit COX-2 upregulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115319 16647138 150351 10490 5973 IL13 IL-13 IL-13 9 1.3 Thus factors that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 can specifically inhibit COX-2 upregulation 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115320 16647138 150351 10490 5973 IL13 IL-13 IL-13 11 1.3 that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 can specifically inhibit COX-2 upregulation 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115321 16647138 150351 17610 9605 PTGS2 COX-2 COX-2 15 16.2 activity such as IL-4 IL-10 and IL-13 can specifically inhibit COX-2 upregulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115322 16647138 150352 17609 9604 PTGS1 COX-1 COX-1 1 4.9 The COX-1 gene also has some putative regulatory sites such as Sp-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115323 16647138 150352 5443 26780 DAND5 SP1 Sp-1 11 0.6 COX-1 gene also has some putative regulatory sites such as Sp-1 Ap-2 NF-IL-6 GATA-1 and a shear-stress response element but the 11 JUMiner_v2.2 1 0 0 2 11205 TotalCon:3<>11205|SP1|6667|Complete__26780|DAND5|199699|No_GeneRif__9514|PSG1|5669|Complete__<>AvaiableGeneRif=2<>BEST:11205|SP1|0.000506004165608438<>ScoreDetail__9514|PSG1|0.000292956911762725__11205|SP1|0.000506004165608438__ 0 0 0 0 0 115324 16647138 150352 22027 11742 TFAP2A AP-2 Ap-2 12 1.6 gene also has some putative regulatory sites such as Sp-1 Ap-2 NF-IL-6 GATA-1 and a shear-stress response element but the location 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115325 16647138 150352 8159 4170 GATA1 GATA1 GATA-1 14 0.6 has some putative regulatory sites such as Sp-1 Ap-2 NF-IL-6 GATA-1 and a shear-stress response element but the location of these 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115326 16647138 150352 17610 9605 PTGS2 COX-2 COX-2 32 16.2 location of these sites differs considerably from those in the COX-2 gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115327 16647138 150353 17609 9604 PTGS1 COX-1 COX-1 0 4.9 COX-1 does not respond to NF-_amp_#x3ba B as intensely as COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115328 16647138 150353 17610 9605 PTGS2 COX-2 COX-2 9 16.2 COX-1 does not respond to NF-_amp_#x3ba B as intensely as COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115329 16647138 150354 17609 9604 PTGS1 COX-1 COX-1 5 4.9 In rat and ovine brain COX-1 and COX-2 immunoreactivities are present in discrete neuronal populations distributed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115330 16647138 150354 17610 9605 PTGS2 COX-2 COX-2 5 16.2 In rat and ovine brain COX-1 and COX-2 immunoreactivities are present in discrete neuronal populations distributed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115331 16647138 150354 17610 9605 PTGS2 COX-2 COX-2 7 16.2 In rat and ovine brain COX-1 and COX-2 immunoreactivities are present in discrete neuronal populations distributed in distinct 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115332 16647138 150355 17609 9604 PTGS1 COX-1 COX-1 0 4.9 COX-1 immunoreactivity is enriched in midbrain pons and medulla ( Breder 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115333 16647138 150355 17610 9605 PTGS2 COX-2 COX-2 16 16.2 midbrain pons and medulla ( Breder et al. 1995 whereas COX-2 immunoreactivity prevails in neurons and glial cells of hippocampus hypothalamus 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115334 16647138 150356 17610 9605 PTGS2 COX-2 COX-2 6 16.2 In neurons astrocytes and microglial cells COX-2 immunoreactivity is localized to the perinuclear regions ( Tomimoto et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115335 16647138 150357 17610 9605 PTGS2 COX-2 COX-2 3 16.2 The expression of COX-2 is markedly increased in microglial cells after intraperitoneal administration of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115336 16647138 150357 10676 6121 IRF6 LPS LPS 15 0.3 increased in microglial cells after intraperitoneal administration of lipopolysaccharide (LPS), LPS whereas neuronal COX-2 remains unchanged ( Elmquist et al. 1997 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115337 16647138 150357 17610 9605 PTGS2 COX-2 COX-2 18 16.2 cells after intraperitoneal administration of lipopolysaccharide (LPS), LPS whereas neuronal COX-2 remains unchanged ( Elmquist et al. 1997 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115338 16647138 150358 17610 9605 PTGS2 COX-2 COX-2 3 16.2 In microglial cells COX-2 expression and ability to release PGE 2 TXA 2 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115339 16647138 150358 10676 6121 IRF6 LPS LPS 21 0.3 PGE 2 TXA 2 and TXB 2 upon stimulation by LPS are several times higher than in astrocytes but lower than 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115340 16647138 150359 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 induction in microglia by proinflammatory stimuli is apparently similar to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115341 16647138 150360 13733 7422 MT-CO3 COX3 COX-3 0 4.6 COX-3 is a new acetaminophen-sensitive isoform of the COX family 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115342 16647138 150360 17610 9605 PTGS2 COX COX 8 2.9 COX-3 is a new acetaminophen-sensitive isoform of the COX family 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115343 16647138 150361 13733 7422 MT-CO3 COX3 COX-3 8 4.6 Although different pharmacological properties have been described for COX-3 compared with COX-1 or COX-2 enzymes many investigators consider it 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115344 16647138 150361 17609 9604 PTGS1 COX-1 COX-1 11 4.9 different pharmacological properties have been described for COX-3 compared with COX-1 or COX-2 enzymes many investigators consider it to be a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115345 16647138 150361 17610 9605 PTGS2 COX-2 COX-2 13 16.2 properties have been described for COX-3 compared with COX-1 or COX-2 enzymes many investigators consider it to be a splice variant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115346 16647138 150361 17609 9604 PTGS1 COX-1 COX-1 25 4.9 many investigators consider it to be a splice variant of COX-1 ( Chandrasekharan et al. 2002 and Davies et al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115347 16647138 150362 13733 7422 MT-CO3 COX3 COX-3 1 4.6 Thus COX-3 is a product of the COX-1 gene but retains intron 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115348 16647138 150362 17609 9604 PTGS1 COX-1 COX-1 7 4.9 Thus COX-3 is a product of the COX-1 gene but retains intron 1 in its mRNA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115349 16647138 150363 13733 7422 MT-CO3 COX3 COX-3 0 4.6 COX-3 is a glycoprotein 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115350 16647138 150364 13733 7422 MT-CO3 COX3 COX-3 3 4.6 Comparison of canine COX-3 activity with murine COX-1 and COX-2 demonstrates that analgesic/antipyretic analgesic 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115351 16647138 150364 17609 9604 PTGS1 COX-1 COX-1 7 4.9 Comparison of canine COX-3 activity with murine COX-1 and COX-2 demonstrates that analgesic/antipyretic analgesic antipyretic drugs such as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115352 16647138 150364 17610 9605 PTGS2 COX-2 COX-2 7 16.2 Comparison of canine COX-3 activity with murine COX-1 and COX-2 demonstrates that analgesic/antipyretic analgesic antipyretic drugs such as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115353 16647138 150364 17610 9605 PTGS2 COX-2 COX-2 9 16.2 Comparison of canine COX-3 activity with murine COX-1 and COX-2 demonstrates that analgesic/antipyretic analgesic antipyretic drugs such as acetaminophen phenacetin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115354 16647138 150364 13733 7422 MT-CO3 COX3 COX-3 23 4.6 drugs such as acetaminophen phenacetin antipyrine and dipyrone selectively inhibit COX-3 and some nonsteroidal anti-inflammatory drugs potently inhibit COX-3 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115355 16647138 150364 13733 7422 MT-CO3 COX3 COX-3 31 4.6 selectively inhibit COX-3 and some nonsteroidal anti-inflammatory drugs potently inhibit COX-3 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115356 16647138 150365 13733 7422 MT-CO3 COX3 COX-3 3 4.6 Thus inhibition of COX-3 could represent a primary central mechanism by which these drugs 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115357 16647138 150366 13733 7422 MT-CO3 COX3 COX-3 0 4.6 COX-3 mRNA expression is highest in choroid plexus and spinal cord 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115358 16647138 150367 13733 7422 MT-CO3 COX3 COX-3 0 4.6 COX-3 mRNA levels are also higher in major brain arteries and 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115359 16647138 150368 13733 7422 MT-CO3 COX3 COX-3 4 4.6 The expression pattern of COX-3 mRNA in the rat CNS primarily relates to the vascular 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115360 16647138 150368 23681 19683 UHMK1 KIS Kis 21 0.6 relates to the vascular density of a given region ( Kis et al. 2004 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 115361 16647138 150369 13733 7422 MT-CO3 COX3 COX-3 4 4.6 The expression studies of COX-3 mRNA in primary cultures of neurons astrocytes endothelial cells pericytes 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115362 16647138 150369 13733 7422 MT-CO3 COX3 COX-3 24 4.6 pericytes and choroidal epithelial cells indicate that the mRNA of COX-3 is present in all of these cell types except neurons 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115363 16647138 150370 13733 7422 MT-CO3 COX3 COX-3 6 4.6 Cerebral endothelial cells showed the highest COX-3 expression ( Kis et al. 2003 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115364 16647138 150370 23681 19683 UHMK1 KIS Kis 9 0.6 Cerebral endothelial cells showed the highest COX-3 expression ( Kis et al. 2003 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 115365 16647138 150371 13733 7422 MT-CO3 COX3 COX-3 0 4.6 COX-3 mRNA was cloned and sequenced from rat cerebral endothelial cells 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115366 16647138 150372 17609 9604 PTGS1 COX-1 COX-1 9 4.9 Sequence analysis indicated that the 98-base-pair intron 1 of COX-1 gene remains unprocessed in COX-3 inducing a frameshift mutation and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115367 16647138 150372 13733 7422 MT-CO3 COX3 COX-3 14 4.6 the 98-base-pair intron 1 of COX-1 gene remains unprocessed in COX-3 inducing a frameshift mutation and a 127-amino-acid open reading frame 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115368 16647138 150372 17610 9605 PTGS2 COX-2 COX-2 30 16.2 a 127-amino-acid open reading frame with no sequence similarity with COX-2 ( Snipes et al. 2005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115369 16647138 150373 13733 7422 MT-CO3 COX3 COX-3 1 4.6 Rat COX-3 is a cytosolic glycoprotein 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115370 16647138 150374 13733 7422 MT-CO3 COX3 COX-3 6 4.6 Amino acid analysis also shows that COX-3 protein has a very basic character with a p I 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115371 16647138 150375 13733 7422 MT-CO3 COX3 COX-3 10 4.6 In addition to the abundance of basic amino acids the COX-3 protein is also very rich in proline (11.81%) 11.81% 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115372 16647138 150377 13733 7422 MT-CO3 COX3 COX-3 5 4.6 To determine the function of COX-3 COS-7 cells were transfected with COX-3 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115373 16647138 150377 13733 7422 MT-CO3 COX3 COX-3 11 4.6 determine the function of COX-3 COS-7 cells were transfected with COX-3 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115374 16647138 150379 13733 7422 MT-CO3 COX3 COX-3 38 4.6 by acetaminophen ( Snipes et al. 2005 suggesting that this COX-3 variant may not be involved in the generation of prostaglandins 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115375 16647138 150380 13733 7422 MT-CO3 COX3 COX-3 7 4.6 This is in contrast to the canine COX-3 which has COX activity 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115376 16647138 150380 17610 9605 PTGS2 COX COX 10 2.9 This is in contrast to the canine COX-3 which has COX activity 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115377 16647138 150381 13733 7422 MT-CO3 COX3 COX-3 8 4.6 Thus there are differences between rat and dog COX-3 proteins 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115378 16647138 150382 17610 9605 PTGS2 COX COX 0 2.9 COX genes may produce a number of splice variants some with 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115379 16647138 150382 17610 9605 PTGS2 COX COX 15 2.9 number of splice variants some with and others without any COX activity ( Kis et al. 2005 Simmons et al. 2005 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115380 16647138 150382 23681 19683 UHMK1 KIS Kis 18 0.6 variants some with and others without any COX activity ( Kis et al. 2005 Simmons et al. 2005 and Snipes et 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 115381 16647138 150383 13733 7422 MT-CO3 COX3 COX-3 8 4.6 Collectively these studies suggest that dogs possess a COX-3 splice variant with cyclooxygenase activity whereas rats have a COX-3 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115382 16647138 150383 13733 7422 MT-CO3 COX3 COX-3 18 4.6 COX-3 splice variant with cyclooxygenase activity whereas rats have a COX-3 splice variant that lacks cyclooxygenase activity 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115383 16647138 150384 13733 7422 MT-CO3 COX3 COX-3 14 4.6 settled only when information on expression properties and roles of COX-3 variants in various mammalian species becomes available ( Table 1 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115384 16647138 150386 11934 6664 LOX LOX LOX 1 3.3 Lipoxygenases (LOX) LOX 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115385 16647138 150387 11934 6664 LOX LOX LOX 11 3.3 at which they oxidize arachidonic acid characterizes the lipoxygenases (LOX) LOX 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115386 16647138 150388 604 435 ALOX5 5-LOX 5-LOX 9 4.7 The biosynthesis of leukotrienes including 5-hydroxyeicosatetraenoic acid (5-HETE), 5-HETE involves 5-LOX 12-LOX the most common LOX in the brain ( Hambrecht 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115387 16647138 150388 606 429 ALOX12 12-LOX 12-LOX 10 3.1 biosynthesis of leukotrienes including 5-hydroxyeicosatetraenoic acid (5-HETE), 5-HETE involves 5-LOX 12-LOX the most common LOX in the brain ( Hambrecht et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115388 16647138 150388 11934 6664 LOX LOX LOX 14 3.3 5-hydroxyeicosatetraenoic acid (5-HETE), 5-HETE involves 5-LOX 12-LOX the most common LOX in the brain ( Hambrecht et al. 1987 with its 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115389 16647138 150389 17609 9604 PTGS1 COX-1 COX-1 28 4.9 of affecting the cerebral circulation in a comparable manner to COX-1 and 2 pathways 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115390 16647138 150389 17610 9605 PTGS2 COX-2 COX-2 28 16.2 of affecting the cerebral circulation in a comparable manner to COX-1 and 2 pathways 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115391 16647138 150390 11934 6664 LOX LOX LOX 0 3.3 LOX are non-heme iron-containing dioxygenases that insert molecular oxygen into arachidonic 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115392 16647138 150392 11934 6664 LOX LOX LOX 0 3.3 LOX have a molecular mass of 75 to 78 kDa 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115393 16647138 150396 11934 6664 LOX LOX LOX 6 3.3 Like non-neural tissues three forms of LOX are present in the brain 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115394 16647138 150397 604 435 ALOX5 5-LOX 5-LOX 2 4.7 They include 5-LOX 12-LOX and 15-LOX 12-LOX catalyzes the stereospecific incorporation of molecular 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115395 16647138 150397 606 429 ALOX12 12-LOX 12-LOX 3 3.1 They include 5-LOX 12-LOX and 15-LOX 12-LOX catalyzes the stereospecific incorporation of molecular oxygen 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115396 16647138 150397 606 429 ALOX12 12-LOX 12-LOX 6 3.1 They include 5-LOX 12-LOX and 15-LOX 12-LOX catalyzes the stereospecific incorporation of molecular oxygen into the C-12 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115397 16647138 150397 606 429 ALOX12 12-LOX 12-LOX 38 3.1 cellular glutathione peroxidase to 12-HETE ( Li et al. 1997 12-LOX has been cloned and characterized from rat brain ( Watanabe 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115398 16647138 150403 604 435 ALOX5 5-LOX 5-LOX 0 4.7 5-LOX and 15-LOX have also been sequenced from several non-neural sources 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115399 16647138 150404 604 435 ALOX5 5-LOX 5-LOX 13 4.7 molecular mass of 78 kDa and share considerable homology with 5-LOX and 15-LOX from soybean 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115400 16647138 150405 11934 6664 LOX LOX LOX 0 3.3 LOX also catalyze a dehydration reaction generating an unstable epoxide intermediate 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115401 16647138 150405 12108 6709 LTA LTA LTA 14 0.0 reaction generating an unstable epoxide intermediate leukotriene A 4 (LTA LTA 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115402 16647138 150406 12108 6709 LTA LTA LTA 0 0.0 LTA 4 is metabolized to LTB 4 by LTA 4 hydrolase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115403 16647138 150406 12110 6711 LTB LTB LTB 5 0.0 LTA 4 is metabolized to LTB 4 by LTA 4 hydrolase or to LTC 4 by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115404 16647138 150406 12108 6709 LTA LTA LTA 8 0.0 LTA 4 is metabolized to LTB 4 by LTA 4 hydrolase or to LTC 4 by conjugation of glutathione 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115405 16647138 150407 12108 6709 LTA LTA LTA 0 0.0 LTA 4 is the precursor for the family of cysteinyl leukotrienes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115406 16647138 150408 604 435 ALOX5 5-LOX 5-LOX 0 4.7 5-LOX is present in brain tissue and neural cells in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115407 16647138 150409 604 435 ALOX5 5-LOX 5-LOX 7 4.7 Upon cell activation leading to leukotriene synthesis 5-LOX translocates from the cytoplasm to the nuclear envelope 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115408 16647138 150411 605 436 ALOX5AP FLAP FLAP 4 1.3 This enzyme also requires FLAP a nuclear envelope-bound 18 kDa protein that acts as an 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115409 16647138 150412 605 436 ALOX5AP FLAP FLAP 0 1.3 FLAP shows homology with LTC 4 synthase and other microsomal glutathione 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115410 16647138 150412 604 435 ALOX5 5-LOX 5-LOX 18 4.7 other microsomal glutathione transferases but has no enzymic activity itself 5-LOX also contains an Src homology 3 (SH3) SH3 binding motif 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115411 16647138 150412 604 435 ALOX5 5-LOX 5-LOX 36 4.7 binding motif which may be involved in the interaction of 5-LOX protein with growth-factor-receptor-bound protein 2 (Grb2) Grb2 ( Lepley et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115412 16647138 150412 8779 4566 GRB2 GRB2 Grb2 42 0.9 the interaction of 5-LOX protein with growth-factor-receptor-bound protein 2 (Grb2) Grb2 ( Lepley et al. 1996 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115413 16647138 150412 21242 11283 SRC SRC Src 22 0.0 but has no enzymic activity itself 5-LOX also contains an Src homology 3 (SH3) SH3 binding motif which may be involved 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115414 16647138 150413 604 435 ALOX5 5-LOX 5-LOX 8 4.7 In cerebellar granule neurons dexamethasone a glucocorticoid increases 5-LOX mRNA and protein contents 3 h after treatment and this 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115415 16647138 150414 604 435 ALOX5 5-LOX 5-LOX 11 4.7 glucocorticoid antagonist RU486 blocks the stimulatory effect of dexamethasone on 5-LOX expression indicating that dexamethasone increases 5-LOX expression in a glucocorticoid-receptor-dependent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115416 16647138 150414 604 435 ALOX5 5-LOX 5-LOX 17 4.7 effect of dexamethasone on 5-LOX expression indicating that dexamethasone increases 5-LOX expression in a glucocorticoid-receptor-dependent manner ( Uz et al. 2001 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115417 16647138 150415 604 435 ALOX5 5-LOX 5-LOX 10 4.7 These studies also indicate that dexamethasone increases the stability of 5-LOX mRNA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115418 16647138 150419 5353 2615 CYP2B6 P450 P450 1 2.2 Cytochrome P450 epoxygenases (EPOX) EPOX 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115419 16647138 150419 6701 3401 EPHX1 EPOX EPOX 3 2.9 Cytochrome P450 epoxygenases (EPOX) EPOX 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115420 16647138 150420 17610 9605 PTGS2 COX COX 4 2.9 In addition to the COX and LOX pathways the cytochrome P450 (CYP450) CYP450 pathways also 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115421 16647138 150420 11934 6664 LOX LOX LOX 6 3.3 In addition to the COX and LOX pathways the cytochrome P450 (CYP450) CYP450 pathways also catalyze arachidonic 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115422 16647138 150420 5353 2615 CYP2B6 P450 P450 10 2.2 In addition to the COX and LOX pathways the cytochrome P450 (CYP450) CYP450 pathways also catalyze arachidonic acid conversion to biologically 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115423 16647138 150422 6701 3401 EPHX1 EPOX EPOX 0 2.9 EPOX are enzymes that in the presence of NADPH and molecular 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115424 16647138 150423 5353 2615 CYP2B6 P450 P450 6 2.2 Although the levels of various cytochrome P450 enzymes in brain are low it has been shown that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115425 16647138 150424 6701 3401 EPHX1 EPOX EPOX 6 2.9 Recent in situ hybridization studies of EPOX mRNA have confirmed its localization in astrocytes specifically those situated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115426 16647138 150426 5356 2623 CYP2C9 CYP2C9 CYP2C9 3 1.7 In addition adenovirus-mediated CYP2C9 gene transfection and EPOX overexpression in endothelial cells result in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115427 16647138 150426 6701 3401 EPHX1 EPOX EPOX 7 2.9 In addition adenovirus-mediated CYP2C9 gene transfection and EPOX overexpression in endothelial cells result in endothelial cell tube formation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115428 16647138 150426 17610 9605 PTGS2 COX-2 COX-2 20 16.2 endothelial cells result in endothelial cell tube formation by stimulating COX-2 expression and prostacyclin production ( Michaelis et al. 2005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115429 16647138 150427 6701 3401 EPHX1 EPOX EPOX 7 2.9 In endothelial cell cultures the overexpression of EPOX upregulates both endothelial nitric oxide synthase (eNOS) eNOS and PI3-kinase/Akt 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115430 16647138 150427 14538 7876 NOS3 eNOS eNOS 14 2.2 overexpression of EPOX upregulates both endothelial nitric oxide synthase (eNOS) eNOS and PI3-kinase/Akt PI3-kinase Akt pathways 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115431 16647138 150427 16613 8975 PIK3CA PI3 PI3-kinase 16 0.3 upregulates both endothelial nitric oxide synthase (eNOS) eNOS and PI3-kinase/Akt PI3-kinase Akt pathways 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 16561 8947 PI3 0 115432 16647138 150427 543 391 AKT1 AKT Akt 16 0.3 both endothelial nitric oxide synthase (eNOS) eNOS and PI3-kinase/Akt PI3-kinase Akt pathways 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115433 16647138 150428 14538 7876 NOS3 eNOS eNOS 2 2.2 Not only eNOS inhibitors but also PI3-kinase/Akt PI3-kinase Akt signaling pathway inhibitors can 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115434 16647138 150428 16613 8975 PIK3CA PI3 PI3-kinase 6 0.3 Not only eNOS inhibitors but also PI3-kinase/Akt PI3-kinase Akt signaling pathway inhibitors can prevent this upregulation by EPOX 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 16561 8947 PI3 0 115435 16647138 150428 543 391 AKT1 AKT Akt 6 0.3 Not only eNOS inhibitors but also PI3-kinase/Akt PI3-kinase Akt signaling pathway inhibitors can prevent this upregulation by EPOX 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115436 16647138 150428 6701 3401 EPHX1 EPOX EPOX 15 2.9 PI3-kinase Akt signaling pathway inhibitors can prevent this upregulation by EPOX 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115437 16647138 150429 14538 7876 NOS3 eNOS eNOS 4 2.2 This indicates that both eNOS and PI3-kinase/Akt PI3-kinase Akt pathways may mediate the angiogenic effects 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115438 16647138 150429 16613 8975 PIK3CA PI3 PI3-kinase 6 0.3 This indicates that both eNOS and PI3-kinase/Akt PI3-kinase Akt pathways may mediate the angiogenic effects of EETs ( 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 16561 8947 PI3 0 115439 16647138 150429 543 391 AKT1 AKT Akt 6 0.3 This indicates that both eNOS and PI3-kinase/Akt PI3-kinase Akt pathways may mediate the angiogenic effects of EETs ( Kawasaki 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115440 16647138 150430 6701 3401 EPHX1 EPOX EPOX 0 2.9 EPOX gene transfection activates the MARK pathway in endothelial cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115441 16647138 150430 12384 6896 MARK1 MARK MARK 5 1.3 EPOX gene transfection activates the MARK pathway in endothelial cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115442 16647138 150431 6701 3401 EPHX1 EPOX EPOX-derived 5 1.6 Collectively these studies suggest that EPOX-derived EETs modulate angiogenesis via a nitric-oxide-dependent mechanism as well as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115443 16647138 150431 16613 8975 PIK3CA PI3 PI3-kinase 19 0.3 via a nitric-oxide-dependent mechanism as well as via activation of PI3-kinase and MARK pathways ( Wang et al. 2003 and Wang 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 16561 8947 PI3 0 115444 16647138 150431 12384 6896 MARK1 MARK MARK 21 1.3 nitric-oxide-dependent mechanism as well as via activation of PI3-kinase and MARK pathways ( Wang et al. 2003 and Wang et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115445 16647138 150432 5353 2615 CYP2B6 P450 P450 4 2.2 Studies on astroglial cytochrome P450 expression suggest a putative capacity of these enzymes to metabolize 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115446 16647138 150433 5353 2615 CYP2B6 P450 P450 15 2.2 most active steroidogenic cells in the brain expressing neurosteroidogenic cytochrome P450 and producing various neurosteroids 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115447 16647138 150437 17610 9605 PTGS2 COX COX 2 2.9 Roles of COX LOX and EPOX in brain tissue 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115448 16647138 150437 11934 6664 LOX LOX LOX 3 3.3 Roles of COX LOX and EPOX in brain tissue 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115449 16647138 150437 6701 3401 EPHX1 EPOX EPOX 5 2.9 Roles of COX LOX and EPOX in brain tissue 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115450 16647138 150438 17610 9605 PTGS2 COX COX 0 2.9 COX LOX and EPOX are important enzymes involved in the generation 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115451 16647138 150438 11934 6664 LOX LOX LOX 1 3.3 COX LOX and EPOX are important enzymes involved in the generation of 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115452 16647138 150438 6701 3401 EPHX1 EPOX EPOX 3 2.9 COX LOX and EPOX are important enzymes involved in the generation of oxygenated derivatives 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115453 16647138 150439 17610 9605 PTGS2 COX COX 0 2.9 COX enzymes catalyze the conversion of AA into prostaglandins and thromboxanes 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115454 16647138 150439 11934 6664 LOX LOX LOX 11 3.3 enzymes catalyze the conversion of AA into prostaglandins and thromboxanes LOX generates leukotrienes and lipoxins and EPOX activity produces epoxyeicosatrienoic acids 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115455 16647138 150439 6701 3401 EPHX1 EPOX EPOX 17 2.9 into prostaglandins and thromboxanes LOX generates leukotrienes and lipoxins and EPOX activity produces epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115456 16647138 150440 17610 9605 PTGS2 COX COX 16 2.9 to release AA metabolites by reactions catalyzed by PLA 2 COX LOX and EPOX depends upon not only on neural cell 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115457 16647138 150440 11934 6664 LOX LOX LOX 17 3.3 release AA metabolites by reactions catalyzed by PLA 2 COX LOX and EPOX depends upon not only on neural cell type 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115458 16647138 150440 6701 3401 EPHX1 EPOX EPOX 19 2.9 metabolites by reactions catalyzed by PLA 2 COX LOX and EPOX depends upon not only on neural cell type but also 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115459 16647138 150453 11001 28961 KIAA0101 PAF PAF 26 0.3 2 with the generation of PGE 2 LTB 4 and PAF through COX-2 LOX and acetyl-CoA acetyltransferase reactions respectively 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115460 16647138 150453 17610 9605 PTGS2 COX-2 COX-2 28 16.2 the generation of PGE 2 LTB 4 and PAF through COX-2 LOX and acetyl-CoA acetyltransferase reactions respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115461 16647138 150453 11934 6664 LOX LOX LOX 29 3.3 generation of PGE 2 LTB 4 and PAF through COX-2 LOX and acetyl-CoA acetyltransferase reactions respectively 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115462 16647138 150453 12110 6711 LTB LTB LTB 22 0.0 stimulation of iPLA 2 with the generation of PGE 2 LTB 4 and PAF through COX-2 LOX and acetyl-CoA acetyltransferase reactions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115463 16647138 150454 11001 28961 KIAA0101 PAF PAF 22 0.3 as cPLA 2 and is associated with the generation of PAF lipoxins and the pro-resolving prostaglandin PGD 2 ( Gilroy et 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115464 16647138 150454 16457 8891 PGD PGD PGD 28 0.3 with the generation of PAF lipoxins and the pro-resolving prostaglandin PGD 2 ( Gilroy et al. 2004 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115465 16647138 150456 17610 9605 PTGS2 COX-2 COX-2 3 16.2 PLA 2 COX-2 and LOX inhibitors have been used to treat acute inflammation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115466 16647138 150456 11934 6664 LOX LOX LOX 5 3.3 PLA 2 COX-2 and LOX inhibitors have been used to treat acute inflammation and pain 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115467 16647138 150468 17610 9605 PTGS2 COX COX 2 2.9 Involvement of COX and LOX in neurodegeneration 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115468 16647138 150468 11934 6664 LOX LOX LOX 4 3.3 Involvement of COX and LOX in neurodegeneration 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115469 16647138 150473 832 549 AOC2 RAO Rao 34 0.3 mitochondrial oxyradical generation and mild calcium overload ( Sastry and Rao 2000 2 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115470 16647138 150474 17610 9605 PTGS2 COX COX 24 2.9 to neuronal degeneration by the activation of caspases PLA 2 COX and LOX resulting in apoptotic cell death 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115471 16647138 150474 11934 6664 LOX LOX LOX 26 3.3 degeneration by the activation of caspases PLA 2 COX and LOX resulting in apoptotic cell death 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115472 16647138 150475 17610 9605 PTGS2 COX COX 14 2.9 supported by the observation that inhibitors of caspases PLA 2 COX and LOX block apoptosis ( Farooqui et al. 2004 Farooqui 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115473 16647138 150475 11934 6664 LOX LOX LOX 16 3.3 the observation that inhibitors of caspases PLA 2 COX and LOX block apoptosis ( Farooqui et al. 2004 Farooqui and Horrocks 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115474 16647138 150476 17610 9605 PTGS2 COX COX 10 2.9 Collective evidence suggests that all isoforms of PLA 2 COX and LOX along with caspases are involved in apoptotic cell 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115475 16647138 150476 11934 6664 LOX LOX LOX 12 3.3 evidence suggests that all isoforms of PLA 2 COX and LOX along with caspases are involved in apoptotic cell death 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115476 16647138 150477 832 549 AOC2 RAO Rao 19 0.3 and redox status also dictates this mode ( Sastry and Rao 2000 2 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115477 16647138 150480 17610 9605 PTGS2 COX COX 3 2.9 The stimulation of COX and LOX isoforms and oxidation of arachidonic acid is harmful 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115478 16647138 150480 11934 6664 LOX LOX LOX 5 3.3 The stimulation of COX and LOX isoforms and oxidation of arachidonic acid is harmful to neurons 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115479 16647138 150483 18723 10261 ROS1 ROS ROS 18 0.0 the increased production of free radicals reactive oxygen species (ROS) ROS and hence for lipid peroxidation and oxidative damage to membrane 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115480 16647138 150484 606 429 ALOX12 12-LOX 12-LOX 3 3.1 The action of 12-LOX produces lipid hydroperoxides 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115481 16647138 150489 17610 9605 PTGS2 COX COX 2 2.9 Involvement of COX and LOX in pain state 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115482 16647138 150489 11934 6664 LOX LOX LOX 4 3.3 Involvement of COX and LOX in pain state 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115483 16647138 150493 8612 4458 GPI PGI PGI 11 0.6 behavior in rats can be produced by peripheral administration of PGI 2 and PGE 2 ( Taiwo and Levine 1990 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000317087492660012<>ScoreDetail__1044|BGN|0.000317087492660012__4458|GPI|0.000299625468164794__ 0 0 0 0 0 115484 16647138 150494 17610 9605 PTGS2 COX COX 3 2.9 The action of COX enzymes on AA generates these metabolites 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115485 16647138 150495 17609 9604 PTGS1 COX-1 COX-1 0 4.9 COX-1 and COX-2 play a central role in the induction of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115486 16647138 150495 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-1 and COX-2 play a central role in the induction of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115487 16647138 150495 17610 9605 PTGS2 COX-2 COX-2 2 16.2 COX-1 and COX-2 play a central role in the induction of nociception produced 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115488 16647138 150496 17610 9605 PTGS2 COX-2 COX-2 6 16.2 An increase in the expression of COX-2 activity accompanies the induction of nociception ( Svensson and Yaksh 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115489 16647138 150497 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 expression and its activity in neuropathic pain are controversial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115490 16647138 150498 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 levels in the dorsal spinal cord increase following a L5/L6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115491 16647138 150498 17610 9605 PTGS2 COX-2 COX-2 26 16.2 Zhao et al. 2000 and intrathecal or local injections of COX-2 inhibitors prevent the development of nociception 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115492 16647138 150499 17610 9605 PTGS2 COX-2 COX-2 10 16.2 In contrast only a very small change in spinal cord COX-2 mRNA and protein expression follows the spared nerve injury model 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115493 16647138 150499 17610 9605 PTGS2 COX-2 COX-2 30 16.2 model of partial nerve injury in the rat and selective COX-2 inhibition does not alter the nociception 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115494 16647138 150500 17610 9605 PTGS2 COX-2 COX-2 3 16.2 This indicates that COX-2 does not play a role in the development and maintenance 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115495 16647138 150501 17610 9605 PTGS2 COX COX-2-generated 20 0.3 as well as peripheral nociceptive mechanisms and both mechanisms involve COX-2-generated metabolites 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115496 16647138 150503 17610 9605 PTGS2 COX COX-isozyme-deficient 14 0.3 (hot-plate) hot-plate and slowly developing diffuse pain (writhing) writhing with COX-isozyme-deficient mice indicate that COX-3 plays an important role in chronic 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115497 16647138 150503 13733 7422 MT-CO3 COX3 COX-3 18 4.6 developing diffuse pain (writhing) writhing with COX-isozyme-deficient mice indicate that COX-3 plays an important role in chronic pain and inflammation in 15 JUMiner_v2.2 1 0 0 2 9604 TotalCon:2<>7422|MT-CO3|4514|Complete__9604|PTGS1|5742|Complete__<>AvaiableGeneRif=2<>BEST:9604|PTGS1|0.000697785081067428<>ScoreDetail__7422|MT-CO3|0.000248680225172027__9604|PTGS1|0.000697785081067428__ 0 0 0 0 0 115498 16647138 150504 17610 9605 PTGS2 COX COX 7 2.9 Collective evidence suggests that all isoforms of COX enzymes are involved in pain transmission processes in brain and 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115499 16647138 150506 17610 9605 PTGS2 COX COX 2 2.9 Involvement of COX and LOX in synaptic plasticity 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115500 16647138 150506 11934 6664 LOX LOX LOX 4 3.3 Involvement of COX and LOX in synaptic plasticity 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115501 16647138 150507 17610 9605 PTGS2 COX-2 COX-2 10 16.2 NMDA receptor-dependent synaptic activity dynamically regulates the expression of the COX-2 gene in brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115502 16647138 150510 17609 9604 PTGS1 COX-1 COX-1 12 4.9 the most abundant prostaglandins generated in the brain through COX-1/COX-2 COX-1 COX-2 pathways (PGE PGE 2 PGF 2a and PGD 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115503 16647138 150510 17610 9605 PTGS2 COX-2 COX-2 12 16.2 most abundant prostaglandins generated in the brain through COX-1/COX-2 COX-1 COX-2 pathways (PGE PGE 2 PGF 2a and PGD 2 are 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115504 16647138 150510 16459 8893 PGF PGF PGF 17 0.6 the brain through COX-1/COX-2 COX-1 COX-2 pathways (PGE PGE 2 PGF 2a and PGD 2 are modulators of synaptic activity and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115505 16647138 150510 16457 8891 PGD PGD PGD 21 0.3 COX-1/COX-2 COX-1 COX-2 pathways (PGE PGE 2 PGF 2a and PGD 2 are modulators of synaptic activity and efficacy by exerting 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115506 16647138 150511 17610 9605 PTGS2 COX-2 COX-2 3 16.2 The observation that COX-2 inhibitors block the induction of LTP in hippocampal dentate granules 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115507 16647138 150512 16457 8891 PGD PGD PGD 8 0.3 The addition of PGE 2 but not PGD 2 or PGF 2_amp_#x3b1 reverses COX-2-mediated suppression of LTP 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115508 16647138 150512 16459 8893 PGF PGF PGF 11 0.6 The addition of PGE 2 but not PGD 2 or PGF 2_amp_#x3b1 reverses COX-2-mediated suppression of LTP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115509 16647138 150512 17610 9605 PTGS2 COX-2 COX-2-mediated 15 2.3 PGE 2 but not PGD 2 or PGF 2_amp_#x3b1 reverses COX-2-mediated suppression of LTP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115510 16647138 150513 17610 9605 PTGS2 COX-2 COX-2-induced 10 2.3 These studies suggest that PGE 2 is the effector of COX-2-induced synaptic plasticity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115511 16647138 150514 17610 9605 PTGS2 COX-2 COX-2 3 16.2 The translocation of COX-2 to the nuclear envelope during neural cell stimulation generates eicosanoids 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115512 16647138 150515 17596 9593 PTGER1 EP1 EP1 8 1.2 The interaction of PGE 2 with a nuclear EP1 receptor also results in calcium mobilization and gene transcription ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115513 16647138 150516 17596 9593 PTGER1 EP1 EP1 9 1.2 Collective evidence suggests that cross talk between NMDA and EP1 receptors and generation of AA metabolites may regulate gene expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115514 16647138 150517 11934 6664 LOX LOX LOX-generated 0 0.0 LOX-generated AA metabolites are also implicated in the modulation of synaptic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115515 16647138 150518 606 429 ALOX12 12-LOX 12-LOX 11 3.1 Thus in mechanosensory neurons of the marine mollusk Aplysia californica 12-LOX metabolites act as second messengers and participate in communication with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115516 16647138 150519 604 435 ALOX5 5-LOX 5-LOX 5 4.7 HPETEs and leukotrienes generated by 5-LOX and 12-LOX inhibit neurotransmitter release by modulating calcium and protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115517 16647138 150519 606 429 ALOX12 12-LOX 12-LOX 7 3.1 HPETEs and leukotrienes generated by 5-LOX and 12-LOX inhibit neurotransmitter release by modulating calcium and protein kinase C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115518 16647138 150520 17610 9605 PTGS2 COX COX- 3 1.8 In brain tissue COX- and LOX-generated metabolites of AA may modulate synaptic plasticity not 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115519 16647138 150520 11934 6664 LOX LOX LOX-generated 5 0.1 In brain tissue COX- and LOX-generated metabolites of AA may modulate synaptic plasticity not only through 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115520 16647138 150528 17610 9605 PTGS2 COX-2 COX-2 40 16.2 into the cell ( Kadoya et al. 2003 4-HNE induces COX-2 expression in macrophages 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115521 16647138 150529 17610 9605 PTGS2 COX-2 COX-2 3 16.2 The expression of COX-2 plays an important role in the intensification of inflammatory responses 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115522 16647138 150545 17610 9605 PTGS2 COX COX 10 2.9 A nonenzymic mechanism analogous to the formation of prostaglandins by COX enzymes forms the isoprostanes 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115523 16647138 150559 11629 6493 LAMC2 CSF CSF 5 0.0 F4-NPs occur in cerebrospinal fluid (CSF) CSF from normal individuals 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115524 16647138 150560 11629 6493 LAMC2 CSF CSF 8 0.0 The levels of F4-NP are significantly higher in CSF from patients with Alzheimer's disease ( Reich et al. 2001 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115525 16647138 150564 11001 28961 KIAA0101 PAF PAF 2 0.3 Platelet-activating factor (PAF) PAF 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115526 16647138 150565 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF is a short-lived biologically active ether lipid with diverse physiological 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115527 16647138 150568 11001 28961 KIAA0101 PAF PAF 17 0.3 platelets endothelial cells mast cells neutrophils and neural cells release PAF 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115528 16647138 150569 11001 28961 KIAA0101 PAF PAF 7 0.3 It exerts its biological effects by activating PAF receptors that consequently activate leukocytes stimulate platelet aggregation and induce 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115529 16647138 150570 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF receptors are linked to G-proteins and activate a variety of 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115530 16647138 150571 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF receptors have been cloned from a number of sources including 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115531 16647138 150572 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF activates a wide variety of cells including neutrophils eosinophils monocytes 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115532 16647138 150573 11001 28961 KIAA0101 PAF PAF 4 0.3 The physiological activity of PAF is not limited to its proinflammatory effects 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115533 16647138 150574 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF is also involved in a variety of other settings including 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115534 16647138 150577 11001 28961 KIAA0101 PAF PAF 7 0.3 Mammalian tissues have three different pathways for PAF synthesis ( Honda et al. 2002 and Snyder 1995 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115535 16647138 150582 11001 28961 KIAA0101 PAF PAF 9 0.3 This reaction provides the inter-relationship between the synthesis of PAF and eicosanoids 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115536 16647138 150583 11001 28961 KIAA0101 PAF PAF 4 0.3 The second step of PAF production requires the conversion of lyso-PAF to PAF by the 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115537 16647138 150583 11001 28961 KIAA0101 PAF PAF 12 0.3 step of PAF production requires the conversion of lyso-PAF to PAF by the enzyme acetyl CoA lyso-PAF acetyltransferase 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115538 16647138 150586 11001 28961 KIAA0101 PAF PAF 5 0.3 The synthesis de novo of PAF requires three steps 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115539 16647138 150590 11001 28961 KIAA0101 PAF PAF 7 0.3 The third pathway for the synthesis of PAF is the oxidative fragmentation of phosphatidylcholines 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115540 16647138 150592 11001 28961 KIAA0101 PAF PAF 7 0.3 These 1-O -alkyl phospholipids interact with PAF receptors and induce a variety of biological effects ( Stafforini 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115541 16647138 150595 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF is hydrolyzed by PAF acetylhydrolases found in all mammalian tissues 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115542 16647138 150595 11001 28961 KIAA0101 PAF PAF 4 0.3 PAF is hydrolyzed by PAF acetylhydrolases found in all mammalian tissues ( Snyder 1995 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115543 16647138 150596 11001 28961 KIAA0101 PAF PAF 13 0.3 human plasma LDL-PLA 2 and the other is bovine brain PAF acetylhydrolase ( Arai 2002 and Tjoelker and Stafforini 2000 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115544 16647138 150597 11001 28961 KIAA0101 PAF PAF 9 0.3 Although both are serine-dependent enzymes their ability to hydrolyze PAF is quite different 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115545 16647138 150599 11001 28961 KIAA0101 PAF PAF 3 0.3 In addition to PAF acetylhydrolase activity plasma LDL-PLA 2 also has a high PLA 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115546 16647138 150600 11001 28961 KIAA0101 PAF PAF 1 0.3 Plasma PAF acetylhydrolase has a dual role in metabolism 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115547 16647138 150601 11001 28961 KIAA0101 PAF PAF 4 0.3 It not only inactivates PAF released from inflammatory cells but it also eliminates oxidized fatty 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115548 16647138 150602 11001 28961 KIAA0101 PAF PAF 2 0.3 Bovine brain PAF acetylhydrolase is an _amp_#x3b1 _amp_#x3b2 and _amp_#x3b3 heterotrimer (Mr Mr 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115549 16647138 150603 11001 28961 KIAA0101 PAF PAF 5 0.3 Mammalian tissues have two other PAF acetylhydrolases 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115550 16647138 150608 11001 28961 KIAA0101 PAF PAF 3 0.3 The binding of PAF to PAF receptors results in the activation of diverse intracellular 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115551 16647138 150608 11001 28961 KIAA0101 PAF PAF 5 0.3 The binding of PAF to PAF receptors results in the activation of diverse intracellular signal transduction 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115552 16647138 150610 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF receptor antagonists block all these processes 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115553 16647138 150611 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF stimulates phosphatidylinositol 3-kinase and mitogen-activated protein (MAP) MAP kinase and 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115554 16647138 150611 12337 6871 MAPK1 MAP MAP 7 0.9 PAF stimulates phosphatidylinositol 3-kinase and mitogen-activated protein (MAP) MAP kinase and inhibits adenylate cyclase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115555 16647138 150612 11001 28961 KIAA0101 PAF PAF 1 0.3 Moreover PAF also acts as an intracellular mediator ( Marcheselli and Bazan 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115556 16647138 150613 11001 28961 KIAA0101 PAF PAF 3 0.3 The binding of PAF to intracellular sites elicits gene expression in neuronal and glial 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115557 16647138 150614 11001 28961 KIAA0101 PAF PAF 1 0.3 Furthermore PAF receptors are also involved in the release of prostaglandin E 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115558 16647138 150616 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF also stimulates the inducible isoform of COX-2 ( Bazan et 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115559 16647138 150616 17610 9605 PTGS2 COX-2 COX-2 7 16.2 PAF also stimulates the inducible isoform of COX-2 ( Bazan et al. 1993 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115560 16647138 150617 17610 9605 PTGS2 COX-2 COX-2 5 16.2 An immediate early gene encodes COX-2 which is responsible for prostaglandin synthesis in neuropathological processes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115561 16647138 150618 11001 28961 KIAA0101 PAF PAF 4 0.3 Preincubation of cells with PAF antagonist BN 50730 blocks stimulation of the immediate early gene 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115562 16647138 150618 17610 9605 PTGS2 COX-2 COX-2 17 16.2 50730 blocks stimulation of the immediate early gene responsible for COX-2 ( Bazan et al. 1997 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115563 16647138 150619 11001 28961 KIAA0101 PAF PAF 1 0.3 Thus PAF is associated with short- and long-term responses of cells to 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115564 16647138 150623 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF antagonists block the development of long-term potentiation ( Del Cerro 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115565 16647138 150623 11001 28961 KIAA0101 PAF PAF 32 0.3 and Zorumski 1996 and Kornecki et al. 1996 indicating that PAF modulates long-term potentiation 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115566 16647138 150624 11001 28961 KIAA0101 PAF PAF 5 0.3 In rats the administration of PAF antagonists impairs spatial learning and inhibitory avoidance tests while treatment 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115567 16647138 150624 11001 28961 KIAA0101 PAF PAF 22 0.3 avoidance tests while treatment with a synthetic non-hydrolyzable analog of PAF 1-O -hexadecyl-2-methylcarbamoyl-sn -glycerol-3-phosphocholine enhances memory ( Packard et al. 1996 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115568 16647138 150625 11001 28961 KIAA0101 PAF PAF 3 0.3 Intracarotid infusion of PAF decreases cerebral blood flow with a concomitant increase in the 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115569 16647138 150626 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF administration causes a dose-dependent decrease in spinal cord blood flow 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115570 16647138 150627 11001 28961 KIAA0101 PAF PAF 1 0.3 A PAF receptor antagonist can block this decrease in blood flow ( 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115571 16647138 150628 11001 28961 KIAA0101 PAF PAF 1 0.3 Although PAF does not cross the blood_amp_#x2013 brain barrier itself it induces 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115572 16647138 150629 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF is also an essential component of the intricate mechanisms by 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115573 16647138 150631 11001 28961 KIAA0101 PAF PAF 2 0.3 Involvement of PAF in neurological disorders 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115574 16647138 150632 11001 28961 KIAA0101 PAF PAF 10 0.3 Several pathological processes including allergy inflammation shock and trauma involve PAF ( Ishii et al. 1997 Ishii et al. 1998 Nagase 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115575 16647138 150634 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF was identified as a pathological mediator by injecting it into 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115576 16647138 150634 11001 28961 KIAA0101 PAF PAF 23 0.3 measuring the intensity of inflammation and by the ability of PAF antagonists to block PAF-mediated responses ( Maclennan et al. 1996 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115577 16647138 150634 11001 28961 KIAA0101 PAF PAF-mediated 27 0.0 inflammation and by the ability of PAF antagonists to block PAF-mediated responses ( Maclennan et al. 1996 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115578 16647138 150635 11001 28961 KIAA0101 PAF PAF 3 0.3 Excessive levels of PAF are associated with neuronal injury in brain tissue and are 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115579 16647138 150636 11001 28961 KIAA0101 PAF PAF 2 0.3 Administration of PAF antagonists has beneficial effects in various models of cerebral ischemia 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115580 16647138 150637 11001 28961 KIAA0101 PAF PAF 0 0.3 PAF activates inflammatory cells and increases vasopermeability a role it may 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115581 16647138 150638 11001 28961 KIAA0101 PAF PAF 2 0.3 Administration of PAF antagonists improves the neurological score of patients with multiple sclerosis 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115582 16647138 150639 15991 8574 PAFAH1B1 MDS MDS 18 1.2 neuro-developmental syndrome Miller_amp_#x2013 Dieker lissencephaly or Miller_amp_#x2013 Dieker syndrome (MDS) MDS 1 JUMiner_v2.2 1 0 0 2 12851 TotalCon:2<>8574|PAFAH1B1|5048|Complete__12851|YWHAE|7531|Complete__<>AvaiableGeneRif=2<>BEST:12851|YWHAE|0.000443819552678434<>ScoreDetail__12851|YWHAE|0.000443819552678434__8574|PAFAH1B1|0.000427084972593418__ 0 0 0 0 0 115583 16647138 150641 15991 8574 PAFAH1B1 MDS MDS 0 1.2 MDS is caused by a defect in the LIS-1 gene which 1 JUMiner_v2.2 1 0 0 2 12851 TotalCon:2<>8574|PAFAH1B1|5048|Complete__12851|YWHAE|7531|Complete__<>AvaiableGeneRif=2<>BEST:12851|YWHAE|0.000443819552678434<>ScoreDetail__12851|YWHAE|0.000443819552678434__8574|PAFAH1B1|0.000427084972593418__ 0 0 0 0 0 115584 16647138 150641 15991 8574 PAFAH1B1 LIS1 LIS-1 8 1.7 MDS is caused by a defect in the LIS-1 gene which has been mapped to ILS/MDS ILS MDS chromosome 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115585 16647138 150641 15991 8574 PAFAH1B1 MDS MDS 15 1.2 the LIS-1 gene which has been mapped to ILS/MDS ILS MDS chromosome 17p 13.3 1 JUMiner_v2.2 1 0 0 2 12851 TotalCon:2<>8574|PAFAH1B1|5048|Complete__12851|YWHAE|7531|Complete__<>AvaiableGeneRif=2<>BEST:12851|YWHAE|0.000443819552678434<>ScoreDetail__12851|YWHAE|0.000443819552678434__8574|PAFAH1B1|0.000427084972593418__ 0 0 0 0 0 115586 16647138 150643 15991 8574 PAFAH1B1 MDS MDS 6 1.2 Seizures and severe mental retardation characterize MDS ( Hattori et al. 1994 and Walsh 1998 1 JUMiner_v2.2 1 0 0 2 12851 TotalCon:2<>8574|PAFAH1B1|5048|Complete__12851|YWHAE|7531|Complete__<>AvaiableGeneRif=2<>BEST:12851|YWHAE|0.000443819552678434<>ScoreDetail__12851|YWHAE|0.000443819552678434__8574|PAFAH1B1|0.000427084972593418__ 0 0 0 0 0 115587 16647138 150644 11001 28961 KIAA0101 PAF PAF 6 0.3 In models of lissencephaly in vitro PAF agonists and antagonists can alter migration of cerebral granule and 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115588 16647138 150644 11001 28961 KIAA0101 PAF PAF 21 0.3 alter migration of cerebral granule and hippocampal cells indicating that PAF may act as a neuronal migration stop signal ( Adachi 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115589 16647138 150645 11001 28961 KIAA0101 PAF PAF-mediated 4 0.0 Collective evidence suggests that PAF-mediated processes are involved in the pathogenesis of many neurological conditions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115590 16647138 150652 16457 8891 PGD PGD PGD 0 0.3 PGD 2 and PGI 2 are generally vasorelaxants 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115591 16647138 150652 8612 4458 GPI PGI PGI 3 0.6 PGD 2 and PGI 2 are generally vasorelaxants 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000317087492660012<>ScoreDetail__1044|BGN|0.000317087492660012__4458|GPI|0.000299625468164794__ 0 0 0 0 0 115592 16647138 150653 16459 8893 PGF PGF PGF 0 0.6 PGF 2_amp_#x3b1 and TXA 2 are constrictors and the effects of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115593 16647138 150656 8612 4458 GPI PGI PGI 13 0.6 in systemic blood pressure cause the release of PGE 2 PGI 2 and PGF 2_amp_#x3b1 from brain ( Chemtob et al. 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000317087492660012<>ScoreDetail__1044|BGN|0.000317087492660012__4458|GPI|0.000299625468164794__ 0 0 0 0 0 115594 16647138 150656 16459 8893 PGF PGF PGF 17 0.6 pressure cause the release of PGE 2 PGI 2 and PGF 2_amp_#x3b1 from brain ( Chemtob et al. 1990a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115595 16647138 150657 8612 4458 GPI PGI PGI 0 0.6 PGI 2 which is released in response to hypercapnia hypotension and 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000317087492660012<>ScoreDetail__1044|BGN|0.000317087492660012__4458|GPI|0.000299625468164794__ 0 0 0 0 0 115596 16647138 150671 606 429 ALOX12 12-LOX 12-LOX 3 3.1 Cloned rat brain 12-LOX generates some 15-HETE ( Watanabe et al. 1993 15-LOX also 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115597 16647138 150674 5353 2615 CYP2B6 P450 P450 5 2.2 EETs and 20-HETE products of P450 arachidonic acid epoxygenase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115598 16647138 150675 5353 2615 CYP2B6 P450 P450 9 2.2 Brain parenchymal tissue metabolizes arachidonic acid via the cytochrome P450 epoxygenase to epoxyeicosatrienoic acids (EETs), EETs which can dilate cerebral 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115599 16647138 150682 5353 2615 CYP2B6 P450 P450 8 2.2 Treatment of the donor vessels with a cytochrome P450 epoxygenase inhibitor (PPOH) PPOH eliminated dilator responses in both donor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115600 16647138 150687 5353 2615 CYP2B6 P450 P450 1 2.2 Another P450 metabolite of arachidonic acid 20-HETE is a potent vasoconstrictor decreasing 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115601 16647138 150700 5353 2615 CYP2B6 P450 P450 2 2.2 Inhibition of P450 epoxygenase activity blocked the functional hyperemia in response to stimulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115602 16647138 150719 17609 9604 PTGS1 COX-1 COX-1 18 4.9 s and both the non-selective inhibitor indomethacin and the selective COX-1 inhibitor SC-560 reduced photolysis-induced hyperemia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115603 16647138 150720 17610 9605 PTGS2 COX-2 COX-2 1 16.2 The COX-2 inhibitor NS-398 was ineffective as were two cytochrome P450 antagonists 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115604 16647138 150720 5353 2615 CYP2B6 P450 P450 10 2.2 The COX-2 inhibitor NS-398 was ineffective as were two cytochrome P450 antagonists (MS-PPOH MS-PPOH and miconazole suggesting that COX-2 and P450 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115605 16647138 150720 17610 9605 PTGS2 COX-2 COX-2 17 16.2 two cytochrome P450 antagonists (MS-PPOH MS-PPOH and miconazole suggesting that COX-2 and P450 metabolites do not play a significant role in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115606 16647138 150720 5353 2615 CYP2B6 P450 P450 19 2.2 P450 antagonists (MS-PPOH MS-PPOH and miconazole suggesting that COX-2 and P450 metabolites do not play a significant role in vasodilation as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115607 16647138 150720 17609 9604 PTGS1 COX-1 COX-1 32 4.9 not play a significant role in vasodilation as compared to COX-1 metabolites 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115608 16647138 150725 17609 9604 PTGS1 COX-1 COX-1 6 4.9 (2006) 2006 observed dense immunohistochemical staining for COX-1 but not COX-2 in the astrocytic endfeet that ensheath cortical 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115609 16647138 150725 17610 9605 PTGS2 COX-2 COX-2 9 16.2 (2006) 2006 observed dense immunohistochemical staining for COX-1 but not COX-2 in the astrocytic endfeet that ensheath cortical arterioles as well 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115610 16647138 150727 17609 9604 PTGS1 COX-1 COX-1 22 4.9 that is initiated by neural activity using a mechanism involving COX-1 metabolites 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115611 16647138 150737 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 expression and prostaglandin E2 production are enhanced in the spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115612 16647138 150741 17596 9593 PTGER1 EP1 EP1 6 1.2 PGE 2 mediated through the EP1 receptor has a possible role in the spinal cord ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115613 16647138 150742 17596 9593 PTGER1 EP1 EP1 0 1.2 EP1 receptors are coupled to calcium ion mobilization and their activation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115614 16647138 150744 17596 9593 PTGER1 EP1 EP1 4 1.2 (1994a) 1994a reported that an EP1 receptor antagonist dose-dependently antagonized PGE 2 -induced allodynia in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115615 16647138 150746 17596 9593 PTGER1 EP1 EP1 6 1.2 (2004) 2004 demonstrated that a highly selective EP1 receptor antagonist ONO-8711 markedly suppressed PGE 2 -induced Ca 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115616 16647138 150747 17596 9593 PTGER1 EP1 EP1 6 1.2 In addition hybridization in situ revealed EP1 receptor signals in the dorsal root ganglion (DRG) DRG neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115617 16647138 150747 17596 9593 PTGER1 EP1 EP1 24 1.2 DRG neurons but not in the spinal cord indicating that EP1 receptor mRNA is located at the terminals of DRG afferent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115618 16647138 150748 17596 9593 PTGER1 EP1 EP1 1 1.2 The EP1 antagonist also reduced mechanical allodynia induced by von Frey filaments 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115619 16647138 150751 16459 8893 PGF PGF PGF 18 0.6 as a specific target of PGE 2 but not of PGF 2_amp_#x3b1 PGD 2 or PGI 2 which reduced inhibitory glycinergic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115620 16647138 150751 16457 8891 PGD PGD PGD 21 0.3 specific target of PGE 2 but not of PGF 2_amp_#x3b1 PGD 2 or PGI 2 which reduced inhibitory glycinergic synaptic transmission 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115621 16647138 150751 8612 4458 GPI PGI PGI 25 0.6 PGE 2 but not of PGF 2_amp_#x3b1 PGD 2 or PGI 2 which reduced inhibitory glycinergic synaptic transmission at low nanomolar 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000317087492660012<>ScoreDetail__1044|BGN|0.000317087492660012__4458|GPI|0.000299625468164794__ 0 0 0 0 0 115622 16647138 150752 17597 9594 PTGER2 EP2 EP2 12 0.6 glycine receptors occurred via a postsynaptic mechanism involving activation of EP2 receptors cholera-toxin-sensitive G-proteins and cAMP-dependent protein kinase 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115623 16647138 150754 17610 9605 PTGS2 COX-2 COX-2 3 16.2 Constitutive levels of COX-2 in the spinal cord are low but peripheral inflammation upregulates 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115624 16647138 150761 17596 9593 PTGER1 EP1 EP1 0 1.2 EP1 and EP3 agonists had little effect on membrane currents confirming 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115625 16647138 150761 17598 9595 PTGER3 EP3 EP3 0 0.6 EP1 and EP3 agonists had little effect on membrane currents confirming 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115626 16647138 150761 17598 9595 PTGER3 EP3 EP3 2 0.6 EP1 and EP3 agonists had little effect on membrane currents confirming that an 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115627 16647138 150761 17597 9594 PTGER2 EP2 EP2-like 13 0.6 agonists had little effect on membrane currents confirming that an EP2-like receptor was involved 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115628 16647138 150762 17610 9605 PTGS2 COX-2 COX-2 10 16.2 In the brain synaptic activity regulates the basal expression of COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115629 16647138 150764 17610 9605 PTGS2 COX-2 COX-2 1 16.2 Furthermore COX-2 is localized in neuronal dendritic spines where active synapses are 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115630 16647138 150764 17610 9605 PTGS2 COX-2 COX-2 25 16.2 Kaufmann et al. 1996 implying that both constitutive and inducible COX-2 may participate in synaptic plasticity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115631 16647138 150765 17610 9605 PTGS2 COX-2 COX-2 1 16.2 Selective COX-2 inhibition significantly reduced postsynaptic excitability back-propagation of dendritic action-potential-associated Ca 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115632 16647138 150765 17609 9604 PTGS1 COX-1 COX-1 26 4.9 of long-term potentiation in hippocampal dentate granule neurons whereas a COX-1 inhibitor was not effective ( Chen et al. 2002 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115633 16647138 150766 16457 8891 PGD PGD PGD 8 0.3 Exogenous application of PGE 2 but not PGD 2 or PGF 2_amp_#x3b1 effectively reversed all of these actions 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115634 16647138 150766 16459 8893 PGF PGF PGF 11 0.6 Exogenous application of PGE 2 but not PGD 2 or PGF 2_amp_#x3b1 effectively reversed all of these actions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115635 16647138 150767 17610 9605 PTGS2 COX-2 COX-2 13 16.2 consistent with a likely role of PGE 2 generated by COX-2 in the regulation of membrane excitability and long-term synaptic plasticity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115636 16647138 150769 17610 9605 PTGS2 COX COX-2-synthesized 0 0.3 COX-2-synthesized PGE 2 may act on PG receptors within the same 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115637 16647138 150771 17610 9605 PTGS2 COX-2 COX-2 4 16.2 Administration of a selective COX-2 inhibitor to eliminate endogenous PGE 2 reduced somatic and dendritic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115638 16647138 150771 3353 1368 CA1 CA1 CA1 19 0.0 PGE 2 reduced somatic and dendritic membrane excitability in hippocampal CA1 pyramidal neurons in brain slices 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115639 16647138 150772 17610 9605 PTGS2 COX-2 COX-2 31 16.2 amplitude and temporal summation in slices previously treated with a COX-2 inhibitor ( Chen and Bazan 2005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115640 16647138 150778 3353 1368 CA1 CA1 CA1 17 0.0 turn triggered Ca 2 elevations in adjacent neurons in the CA1 hippocampus 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115641 16647138 150781 17609 9604 PTGS1 COX-1 COX-1 17 4.9 is a profound difference between NSAIDs with different selectivities for COX-1 and COX-2 with regard to their effects on the synthesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115642 16647138 150781 17610 9605 PTGS2 COX-2 COX-2 17 16.2 is a profound difference between NSAIDs with different selectivities for COX-1 and COX-2 with regard to their effects on the synthesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115643 16647138 150781 17610 9605 PTGS2 COX-2 COX-2 19 16.2 profound difference between NSAIDs with different selectivities for COX-1 and COX-2 with regard to their effects on the synthesis of endogenous 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115644 16647138 150782 17609 9604 PTGS1 COX-1 COX-1 6 4.9 NSAIDs displaying an inhibitory action on COX-1 increased brain KYNA formation whereas COX-2 selective inhibitors had the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115645 16647138 150782 17610 9605 PTGS2 COX-2 COX-2 12 16.2 an inhibitory action on COX-1 increased brain KYNA formation whereas COX-2 selective inhibitors had the opposite effect 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115646 16647138 150783 17610 9605 PTGS2 COX COX 21 2.9 and lowering in brain KYNA levels following the administration of COX inhibitors suggesting that PGs tonically modulate KYNA metabolism 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115647 16647138 150784 17609 9604 PTGS1 COX-1 COX-1 14 4.9 acid formation induced by NSAIDs displaying an inhibitory action on COX-1 could possibly contribute to a reduction in glutamatergic transmission along 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115648 16647138 150788 606 429 ALOX12 12-LOX 12-LOX 23 3.1 function in the central nervous system has been focused on 12-LOX 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115649 16647138 150789 606 429 ALOX12 12-LOX 12-LOX 2 3.1 Detection of 12-LOX mRNA was reported in neuronal cultures ( Palluy et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115650 16647138 150790 606 429 ALOX12 12-LOX 12-LOX 12 3.1 several groups suggested that arachidonic acid or one of its 12-LOX metabolites might function as a retrograde messenger in long-term potentiation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115651 16647138 150791 11934 6664 LOX LOX LOX 11 3.3 effects of arachidonic acid were antagonized by nordihydroguaiaretic acid a LOX inhibitor indicating that its metabolites were responsible for these effects 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115652 16647138 150792 606 429 ALOX12 12-LOX 12-LOX 1 3.1 Two 12-LOX metabolites of arachidonic acid 12-hydroxyeicosatrienoic acid (HETE) HETE and 12-hydroperoxyeicosatetraenoic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115653 16647138 150794 606 429 ALOX12 12-LOX 12-LOX 4 3.1 (1990) 1990 demonstrated that the 12-LOX pathway of arachidonic acid metabolism in cerebral cortical slices was 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115654 16647138 150797 606 429 ALOX12 12-LOX 12-LOX 4 3.1 However in this instance 12-LOX products attenuated depolarization-evoked accumulation of intraterminal free Ca 2 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115655 16647138 150798 606 429 ALOX12 12-LOX 12-LOX 19 3.1 positive modulator of the glutamate release involved in long-term potentiation 12-LOX metabolites provide signals designed to limit neurotransmitter release 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115656 16647138 150799 606 429 ALOX12 12-LOX 12-LOX 6 3.1 Further evidence for an involvement of 12-LOX rather than 5-LOX or a cyclooxygenase in homosynaptic long-term depression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115657 16647138 150799 604 435 ALOX5 5-LOX 5-LOX 9 4.7 Further evidence for an involvement of 12-LOX rather than 5-LOX or a cyclooxygenase in homosynaptic long-term depression of the hippocampus 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115658 16647138 150800 606 429 ALOX12 12-LOX 12-LOX 1 3.1 The 12-LOX inhibitor baicalein was the most effective in blocking hippocampal LTD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115659 16647138 150800 606 429 ALOX12 12-LOX 12-LOX 20 3.1 blocking hippocampal LTD ( Normandin et al. 1996 indicating that 12-LOX metabolites may be important factors controlling the expression of hippocampal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115660 16647138 150802 606 429 ALOX12 12-LOX 12-LOX 32 3.1 and not to changes in the number of binding sites 12-LOX inhibitors preferentially reduced the PLA 2 -induced decrease in AMPA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115661 16647138 150803 606 429 ALOX12 12-LOX 12-LOX 1 3.1 The 12-LOX inhibitor baicalein totally blocked LTD in the CA1 region of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115662 16647138 150803 3353 1368 CA1 CA1 CA1 9 0.0 The 12-LOX inhibitor baicalein totally blocked LTD in the CA1 region of hippocampal slices 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115663 16647138 150804 606 429 ALOX12 12-LOX 12-LOX 15 3.1 with the concept that arachidonic acid metabolites produced by the 12-LOX pathway could account for AMPA receptor alterations for both LTP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115664 16647138 150806 606 429 ALOX12 12-LOX 12-LOX 13 3.1 a recent multidisciplinary study gave evidence for a role of 12-LOX metabolites in metabotropic-glutamate receptor-dependent long-term depression at hippocampal CA3_amp_#x2013 CA1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115665 16647138 150806 3353 1368 CA1 CA1 CA1 22 0.0 12-LOX metabolites in metabotropic-glutamate receptor-dependent long-term depression at hippocampal CA3_amp_#x2013 CA1 synapses 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115666 16647138 150807 606 429 ALOX12 12-LOX 12-LOX 8 3.1 Their results strongly support the hypothesis that a 12-LOX pathway is required for the induction of metabotropic-glutamate-receptor-dependent LTD but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115667 16647138 150808 606 429 ALOX12 12-LOX 12-LOX 1 3.1 The 12-LOX metabolite of arachidonic acid 12(s)-HPETE 12 s -HPETE appeared to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115668 16647138 150811 5353 2615 CYP2B6 P450 P450 21 2.2 evidence that the metabolites of arachidonic acid generated by cytochrome P450 epoxygenase play a significant role in the modulation of synaptic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115669 16647138 150823 17609 9604 PTGS1 COX-1 COX-1 30 4.9 because of the well-known analgesic and temperature-reducing effects of COX-1/-2 COX-1 -2 inhibitors on patients experiencing these conditions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115670 16647138 150825 17598 9595 PTGER3 EP3 EP3 6 0.6 (1998) 1998 suggested an involvement of the EP3 receptor in febrile responses 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115671 16647138 150826 17598 9595 PTGER3 EP3 EP3-deficient 3 0.6 They demonstrated that EP3-deficient mice failed to show a febrile response to intracerebroventricular injections 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115672 16647138 150827 17596 9593 PTGER1 EP1 EP1 2 1.2 Mice lacking EP1 EP2 and EP4 receptors responded to PGE 2 injections with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115673 16647138 150827 17597 9594 PTGER2 EP2 EP2 3 0.6 Mice lacking EP1 EP2 and EP4 receptors responded to PGE 2 injections with similar 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115674 16647138 150827 17599 9596 PTGER4 EP4 EP4 3 0.6 Mice lacking EP1 EP2 and EP4 receptors responded to PGE 2 injections with similar 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115675 16647138 150827 17599 9596 PTGER4 EP4 EP4 5 0.6 Mice lacking EP1 EP2 and EP4 receptors responded to PGE 2 injections with similar febrile reactions 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115676 16647138 150827 17598 9595 PTGER3 EP3 EP3 26 0.6 to those seen in control mice establishing that the cerebral EP3 receptors are involved in PGE 2 -evoked febrile responses 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115677 16647138 150829 17596 9593 PTGER1 EP1 EP1 6 1.2 (2001) 2001 proposed a role for the EP1 receptor in pain perception 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115678 16647138 150831 17596 9593 PTGER1 EP1 EP1 0 1.2 EP1 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 mice were healthy and fertile but with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115679 16647138 150834 8612 4458 GPI PGI PGI 6 0.6 (1997) 1997 using mice lacking prostacyclin (PGI PGI 2 receptors (IP), IP suggested that these receptors play a 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000317087492660012<>ScoreDetail__1044|BGN|0.000317087492660012__4458|GPI|0.000299625468164794__ 0 0 0 0 0 115680 16647138 150835 17596 9593 PTGER1 EP1 EP1 4 1.2 The observation that both EP1 and IP receptors ( Oida et al. 1995 are expressed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115681 16647138 150836 17596 9593 PTGER1 EP1 EP1 13 1.2 to note that in addition to IP mRNA mRNAs for EP1 EP3 and EP4 were expressed in about 30% 50% and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115682 16647138 150836 17598 9595 PTGER3 EP3 EP3 14 0.6 note that in addition to IP mRNA mRNAs for EP1 EP3 and EP4 were expressed in about 30% 50% and 20% 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115683 16647138 150836 17599 9596 PTGER4 EP4 EP4 14 0.6 note that in addition to IP mRNA mRNAs for EP1 EP3 and EP4 were expressed in about 30% 50% and 20% 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115684 16647138 150836 17599 9596 PTGER4 EP4 EP4 16 0.6 in addition to IP mRNA mRNAs for EP1 EP3 and EP4 were expressed in about 30% 50% and 20% of the 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115685 16647138 150836 17596 9593 PTGER1 EP1 EP1 31 1.2 30% 50% and 20% of the IP-receptor-positive neurons coexpressing the EP1 EP3 and EP4 receptor respectively ( Oida et al. 1995 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115686 16647138 150836 17598 9595 PTGER3 EP3 EP3 32 0.6 50% and 20% of the IP-receptor-positive neurons coexpressing the EP1 EP3 and EP4 receptor respectively ( Oida et al. 1995 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115687 16647138 150836 17599 9596 PTGER4 EP4 EP4 32 0.6 50% and 20% of the IP-receptor-positive neurons coexpressing the EP1 EP3 and EP4 receptor respectively ( Oida et al. 1995 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115688 16647138 150836 17599 9596 PTGER4 EP4 EP4 34 0.6 20% of the IP-receptor-positive neurons coexpressing the EP1 EP3 and EP4 receptor respectively ( Oida et al. 1995 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115689 16647138 150837 17597 9594 PTGER2 EP2 EP2 5 0.6 PGE 2 receptors of the EP2 receptor subtype have been identified as key signaling elements in 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115690 16647138 150838 17597 9594 PTGER2 EP2 EP2 3 0.6 Mice deficient in EP2 receptors completely lacked spinal PGE 2 -evoked hyperalgesia 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115691 16647138 150839 16457 8891 PGD PGD PGD 7 0.3 When small amounts of PGE 2 PGD 2 PGF 2_amp_#x3b1 or PGI 2 were injected intrathecally into 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115692 16647138 150839 16459 8893 PGF PGF PGF 10 0.6 When small amounts of PGE 2 PGD 2 PGF 2_amp_#x3b1 or PGI 2 were injected intrathecally into the spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115693 16647138 150839 8612 4458 GPI PGI PGI 14 0.6 small amounts of PGE 2 PGD 2 PGF 2_amp_#x3b1 or PGI 2 were injected intrathecally into the spinal canal in WT 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000317087492660012<>ScoreDetail__1044|BGN|0.000317087492660012__4458|GPI|0.000299625468164794__ 0 0 0 0 0 115694 16647138 150840 17597 9594 PTGER2 EP2 EP2-deficient 0 0.6 EP2-deficient mice lost this response 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115695 16647138 150841 17597 9594 PTGER2 EP2 EP2 6 0.6 After a peripheral inflammatory stimulus the EP2 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 mice exhibited only a short-lasting peripheral hyperalgesic 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115696 16647138 150844 16457 8891 PGD PGD PGD 6 0.3 (2001) 2001 employing wild-type and DP (PGD PGD 2 -receptor-deficient mice demonstrated that PGD 2 infusions into the 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115697 16647138 150844 16457 8891 PGD PGD PGD 12 0.3 wild-type and DP (PGD PGD 2 -receptor-deficient mice demonstrated that PGD 2 infusions into the lateral ventricles increased non-rapid eye movement 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115698 16647138 150844 18182 15922 REM1 REM REM 28 0.0 increased non-rapid eye movement (NREM), NREM with a decrease in REM sleep 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115699 16647138 150845 16457 8891 PGD PGD PGD 14 0.3 the amounts of NREM and REM sleep were unchanged by PGD 2 infusions demonstrating an involvement of DP receptors in PGD 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115700 16647138 150845 16457 8891 PGD PGD PGD 24 0.3 PGD 2 infusions demonstrating an involvement of DP receptors in PGD 2 -induced NREM sleep 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115701 16647138 150845 18182 15922 REM1 REM REM 9 0.0 In DP-deficient mice however the amounts of NREM and REM sleep were unchanged by PGD 2 infusions demonstrating an involvement 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115702 16647138 150847 17610 9605 PTGS2 COX COX 2 2.9 Gene deletion studies_amp_#x2014 COX and LOX 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115703 16647138 150847 11934 6664 LOX LOX LOX 4 3.3 Gene deletion studies_amp_#x2014 COX and LOX 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115704 16647138 150848 17610 9605 PTGS2 COX COX 3 2.9 The development of COX deficient mice has allowed investigators to study the individual roles 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115705 16647138 150848 17609 9604 PTGS1 COX-1 COX-1 16 4.9 has allowed investigators to study the individual roles of the COX-1 and COX-2 isoforms 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115706 16647138 150848 17610 9605 PTGS2 COX-2 COX-2 16 16.2 has allowed investigators to study the individual roles of the COX-1 and COX-2 isoforms 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115707 16647138 150848 17610 9605 PTGS2 COX-2 COX-2 18 16.2 investigators to study the individual roles of the COX-1 and COX-2 isoforms 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115708 16647138 150850 4829 2294 COX8A COX COX-1-deficient 0 0.3 COX-1-deficient mice have very low (1% 1% of normal PG levels 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115709 16647138 150851 17610 9605 PTGS2 COX COX-2-deficient 0 0.3 COX-2-deficient mice have poor survival rates reduced resolution of gastrointestinal ulcers 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115710 16647138 150852 17610 9605 PTGS2 COX-2 COX-2 22 16.2 these lists and that for the maintenance of normal physiology COX-2 appears to play a more critical role 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115711 16647138 150853 17610 9605 PTGS2 COX COX 13 2.9 which there is evidence for a central role of both COX enzymes is hypophagia (a a reduction in feeding in mice 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115712 16647138 150855 17609 9604 PTGS1 COX-1 COX-1 7 4.9 At 30 to 40 min after IL-1_amp_#x3b2 COX-1 KO mice showed a smaller reduction in milk intake in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115713 16647138 150855 17610 9605 PTGS2 COX-2 COX-2 23 16.2 reduction in milk intake in comparison with wild-type mice whereas COX-2 mice responded more like wild-type animals 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115714 16647138 150856 17610 9605 PTGS2 COX-2 COX-2 9 16.2 However at 90 to 120 min after IL-1_amp_#x3b2 administration COX-2 KO mice showed only small responses while COX-1 KO mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115715 16647138 150856 17609 9604 PTGS1 COX-1 COX-1 17 4.9 IL-1_amp_#x3b2 administration COX-2 KO mice showed only small responses while COX-1 KO mice responded normally 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115716 16647138 150857 17609 9604 PTGS1 COX-1 COX-1 5 4.9 This result suggests that while COX-1 is primarily involved in the early phase of milk intake 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115717 16647138 150857 17610 9605 PTGS2 COX-2 COX-2 16 16.2 is primarily involved in the early phase of milk intake COX-2 is more responsible for the later phase ( Swiergiel and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115718 16647138 150858 17610 9605 PTGS2 COX-2 COX-2- 20 2.3 demonstrated reduced and increased susceptibility to ischemic brain injury in COX-2- and COX-1-deficient mice respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115719 16647138 150858 4829 2294 COX8A COX COX-1-deficient 22 0.3 and increased susceptibility to ischemic brain injury in COX-2- and COX-1-deficient mice respectively 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115720 16647138 150860 17610 9605 PTGS2 COX COX-2-deficient 15 0.3 level of neuronal injury produced by transient global ischemia in COX-2-deficient mice in comparison with wild-type mice 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115721 16647138 150861 17610 9605 PTGS2 COX-2 COX-2 5 16.2 Various lines of evidence implicate COX-2 in fever production 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115722 16647138 150862 10676 6121 IRF6 LPS LPS 11 0.3 enhanced in the brain after peripheral (intraperitoneal) intraperitoneal lipopolysaccharide (LPS) LPS or intravenous and intracerebral IL-1_amp_#x3b2 administration whereas COX-2 inhibitors suppress 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115723 16647138 150862 17610 9605 PTGS2 COX-2 COX-2 19 16.2 lipopolysaccharide (LPS) LPS or intravenous and intracerebral IL-1_amp_#x3b2 administration whereas COX-2 inhibitors suppress the fever induced by these pyrogens ( Cao 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115724 16647138 150864 10676 6121 IRF6 LPS LPS 9 0.3 (1999) 1999 assessed the febrile response to injection of intraperitoneal LPS in COX-1 and COX-2-deficient mice 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115725 16647138 150864 17609 9604 PTGS1 COX-1 COX-1 11 4.9 assessed the febrile response to injection of intraperitoneal LPS in COX-1 and COX-2-deficient mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115726 16647138 150864 17610 9605 PTGS2 COX COX-2-deficient 13 0.3 febrile response to injection of intraperitoneal LPS in COX-1 and COX-2-deficient mice 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115727 16647138 150865 17609 9604 PTGS1 COX-1 COX-1 3 4.9 The wild-type and COX-1 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 mice responded to LPS with a 1_amp_#xb0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115728 16647138 150865 10676 6121 IRF6 LPS LPS 8 0.3 The wild-type and COX-1 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 mice responded to LPS with a 1_amp_#xb0 C rise in temperature whereas the COX-2 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115729 16647138 150865 17610 9605 PTGS2 COX-2 COX-2 17 16.2 LPS with a 1_amp_#xb0 C rise in temperature whereas the COX-2 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 mice displayed no increase in temperature indicating 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115730 16647138 150865 17610 9605 PTGS2 COX-2 COX-2 27 16.2 _amp_#x2212 _amp_#x2212 mice displayed no increase in temperature indicating that COX-2 is necessary for LPS-induced fever production 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115731 16647138 150865 10676 6121 IRF6 LPS LPS-induced 31 0.3 no increase in temperature indicating that COX-2 is necessary for LPS-induced fever production 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115732 16647138 150869 606 429 ALOX12 12-LOX 12-LOX 12 3.1 in locomotor activity were augmented acutely but not chronically in 12-LOX _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 mice ( Walters et al. 2003 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115733 16647138 150870 606 429 ALOX12 12-LOX 12-LOX 7 3.1 Together these results suggest a role for 12-LOX products in morphine and cocaine behavioral responses 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115734 16647138 150873 17610 9605 PTGS2 COX-2 COX-2 2 16.2 Endocannabinoids and COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115735 16647138 150876 6901 3553 FAAH FAAH FAAH 13 2.2 the metabolism of AEA is fatty acid amide hydrolase (FAAH) FAAH 1 JUMiner_v2.2 1 0 0 2 21197 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:21197|FA2H|0.00072133868278608<>ScoreDetail__21197|FA2H|0.00072133868278608__3553|FAAH|0.000480700931337406__ 0 0 0 0 0 115736 16647138 150878 17610 9605 PTGS2 COX-2 COX-2 13 16.2 these hydrolytic pathways endocannabinoids can be selectively oxygenated by a COX-2 pathway ( Kozak and Marnett 2002 and Yu et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115737 16647138 150879 17610 9605 PTGS2 COX-2 COX-2 2 16.2 Inhibition of COX-2 can potentiate the action of these endocannabinoids ( Kim and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115738 16647138 150880 17610 9605 PTGS2 COX-2 COX-2 8 16.2 Furthermore metabolites of AEA and 2-AG derived from COX-2 possess biological activity including the activation of protein kinase C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115739 16647138 150881 17610 9605 PTGS2 COX-2 COX-2 18 16.2 significantly more stable metabolically than free acid PGs suggesting that COX-2 action on endocannabinoids may provide oxygenated lipids with sufficiently long 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115740 16647138 150885 12201 13731 MAEA MAEA MAEA 5 0.3 Incubation with R (+) -methanandamide (MAEA), MAEA which is not a substrate for fatty acid amidohydrolase (FAAH), 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115741 16647138 150885 6901 3553 FAAH FAAH FAAH 15 2.2 which is not a substrate for fatty acid amidohydrolase (FAAH), FAAH produced a similar increase in PGE 2 production as AEA 1 JUMiner_v2.2 1 0 0 2 21197 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:21197|FA2H|0.00072133868278608<>ScoreDetail__21197|FA2H|0.00072133868278608__3553|FAAH|0.000480700931337406__ 0 0 0 0 0 115742 16647138 150886 12201 13731 MAEA MAEA MAEA 12 0.3 inhibited the PGE 2 production induced by either AEA or MAEA a selective COX-2 inhibitor indicating induction of COX-2 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115743 16647138 150886 17610 9605 PTGS2 COX-2 COX-2 15 16.2 2 production induced by either AEA or MAEA a selective COX-2 inhibitor indicating induction of COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115744 16647138 150886 17610 9605 PTGS2 COX-2 COX-2 20 16.2 AEA or MAEA a selective COX-2 inhibitor indicating induction of COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115745 16647138 150887 12201 13731 MAEA MAEA MAEA 2 0.3 AEA and MAEA increased the expression of COX-2 protein an action that AM-251 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115746 16647138 150887 17610 9605 PTGS2 COX-2 COX-2 7 16.2 AEA and MAEA increased the expression of COX-2 protein an action that AM-251 a selective cannabinoid receptor-1-agonist partially 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115747 16647138 150888 17610 9605 PTGS2 COX-2 COX-2 3 16.2 Additionally AEA increased COX-2 promoter activity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115748 16647138 150890 17610 9605 PTGS2 COX-2 COX-2 5 16.2 (2005) 2005 suggested that AEA increases COX-2 expression at the transcriptional level through a cannabinoid-receptor-1-mediated mechanism in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115749 16647138 150893 17610 9605 PTGS2 COX-2 COX-2 7 16.2 (2005) 2005 concluded that oxidation of eCB by COX-2 decreases their level in the hippocampus thus enhancing LTP eCBs 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115750 16647138 150893 6111 19199 DPPA3 Stella Stella 28 1.6 which are generated during robust stimulation of hippocampal slices ( Stella et al. 1997 tonically decrease basal excitatory transmission by modulating 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115751 16647138 150894 3353 1368 CA1 CA1 CA1 18 0.0 would have a disinhibitory effect enhancing transmission with depolarization of CA1 pyramidal neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115752 16647138 150896 4644 2159 CNR1 CB1 CB1 19 0.6 slices was facilitated following treatment with a cannabinoid receptor (CB1) CB1 antagonist revealing a tonic inhibitory influence of eCBs on LTP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115753 16647138 150897 17610 9605 PTGS2 COX-2 COX-2 3 16.2 Conversely inhibition of COX-2 prevented LTP in hippocampal dentate neurons ( Kim and Alger 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115754 16647138 150897 17610 9605 PTGS2 COX-2 COX-2 21 16.2 ( Kim and Alger 2004 leading to the conclusion that COX-2 regulates the formation of CB1 ligands that negatively regulate LTP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115755 16647138 150897 4644 2159 CNR1 CB1 CB1 26 0.6 leading to the conclusion that COX-2 regulates the formation of CB1 ligands that negatively regulate LTP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115756 16647138 150904 19891 29546 SH3YL1 Ray Ray 58 0.9 can contribute to restoration of some function following TBI ( Ray et al. 2002 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115757 16647138 150906 17610 9605 PTGS2 COX COX 6 2.9 Early indications of an involvement of COX and LOX in traumatic brain injury arose from studies on 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115758 16647138 150906 11934 6664 LOX LOX LOX 8 3.3 Early indications of an involvement of COX and LOX in traumatic brain injury arose from studies on feline cerebral 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115759 16647138 150907 16459 8893 PGF PGF PGF 7 0.6 PGE 1 6-keto-PGF 1_amp_#x3b1 and PGF 2_amp_#x3b1 levels in the cerebral cortex were increased and remained 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115760 16647138 150909 11629 6493 LAMC2 CSF CSF 6 0.0 In a subsequent study increased plasma CSF and brain levels of PGE 2 6-keto-PGF 1_amp_#x3b1 thromboxane B 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115761 16647138 150910 606 429 ALOX12 12-LOX 12-LOX 18 3.1 post-injury confirmed the previous observations and demonstrated an involvement of 12-LOX in the injury process 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115762 16647138 150913 16457 8891 PGD PGD PGD 10 0.3 Azelastine an agent that inhibits the release of leukotrienes and PGD 2 from cultured human mast cells ( Shichijo et al. 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115763 16647138 150913 3353 1368 CA1 CA1 CA1 24 0.0 cultured human mast cells ( Shichijo et al. 1998 protected CA1 neurons in hippocampal slices from injury elicited by fluid percussion 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115764 16647138 150914 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 is an important mediator of neuroinflammation ( Feng et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115765 16647138 150916 17597 9594 PTGER2 EP2 EP2 21 0.6 and the apoptosis of cortical cells by acting on the EP2 receptor which in turn activates caspase-3 a pro-apoptotic agent ( 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115766 16647138 150917 17610 9605 PTGS2 COX-2 COX-2 12 16.2 of the rat cerebral cortex caused a bilateral induction of COX-2 mRNA in the cortex and dentate gyrus 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115767 16647138 150918 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 activity was detectable in these areas and persisted in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115768 16647138 150919 17609 9604 PTGS1 COX-1 COX-1 9 4.9 A persistent accumulation of microglial cells and macrophages expressing COX-1 was also observed in human and rat traumatic brain injuries 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115769 16647138 150920 17610 9605 PTGS2 COX-2 COX-2 2 16.2 Upregulation of COX-2 mRNA has also been observed in the rat spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115770 16647138 150921 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 immunoreactivity in this instance was observed only in endothelial cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115771 16647138 150923 17610 9605 PTGS2 COX-2 COX-2 3 16.2 (1998) 1998 observed trauma-induced COX-2 mRNA expression in spinal cord neurons and around blood vessels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115772 16647138 150924 17610 9605 PTGS2 COX-2 COX-2 2 16.2 (2000) 2000 found COX-2 protein almost exclusively in neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115773 16647138 150925 17610 9605 PTGS2 COX-2 COX-2 3 16.2 The effects of COX-2 inhibition on recovery following traumatic brain injury (TBI) TBI in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115774 16647138 150928 17610 9605 PTGS2 COX-2 COX-2 16 16.2 worsening of motor but not cognitive performance and suggested that COX-2 induction following TBI may play a protective role 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115775 16647138 150931 12110 6711 LTB LTB LTB 18 0.0 changes in leukotrienes LTC 4 LTD 4 LTE 4 and LTB 4 in rat cerebrospinal fluid from 10 min to 7 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115776 16647138 150934 12110 6711 LTB LTB LTB 0 0.0 LTB 4 levels were lower and peaked with a two-fold increase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115777 16647138 150943 5353 2615 CYP2B6 P450 P450 7 2.2 Inhibitors of phospholipase A 2 and cytochrome P450 epoxygenase blocked this capacitative Ca 2 entry from the extracellular 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115778 16647138 150945 561 403 ALDH3A2 SLS SLS 2 0.9 Sj_amp_#xf6 gren_amp_#x2013 Larsson syndrome (SLS) SLS is an autosomal recessive disorder associated with increased leukotriene production 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115779 16647138 150948 12110 6711 LTB LTB LTB 12 0.0 of this enzyme is associated with the defective degradation of LTB 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115780 16647138 150949 561 403 ALDH3A2 SLS SLS 17 0.9 concentrations of LTB 4 LTC 4 and 20-OH-LTB 4 in SLS patients ( Willemsen et al. 2001a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115781 16647138 150949 12110 6711 LTB LTB LTB 7 0.0 This results in elevated urinary concentrations of LTB 4 LTC 4 and 20-OH-LTB 4 in SLS patients ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115782 16647138 150950 561 403 ALDH3A2 SLS SLS 0 0.9 SLS is characterized by ichthyosis (thickened thickened fish-like skin spastic paraplegia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115783 16647138 150951 561 403 ALDH3A2 SLS SLS 19 0.9 by the accumulation of aldehyde-modified lipids or fatty alcohols in SLS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115784 16647138 150953 561 403 ALDH3A2 SLS SLS 4 0.9 Although the treatment of SLS patients with the 5-LOX inhibitor (Zileuton) Zileuton blocks peripheral SLS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115785 16647138 150953 604 435 ALOX5 5-LOX 5-LOX 8 4.7 Although the treatment of SLS patients with the 5-LOX inhibitor (Zileuton) Zileuton blocks peripheral SLS symptoms and inhibits LTB 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115786 16647138 150953 561 403 ALDH3A2 SLS SLS 13 0.9 SLS patients with the 5-LOX inhibitor (Zileuton) Zileuton blocks peripheral SLS symptoms and inhibits LTB 4 synthesis it does not improve 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115787 16647138 150953 12110 6711 LTB LTB LTB 17 0.0 5-LOX inhibitor (Zileuton) Zileuton blocks peripheral SLS symptoms and inhibits LTB 4 synthesis it does not improve CNS symptoms ( Willemsen 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115788 16647138 150955 203 10522 ACSM3 SAH SAH 5 0.0 Cerebral ischemia and subarachnoid hemorrhage (SAH) SAH 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115789 16647138 150956 17609 9604 PTGS1 COX-1 COX-1 2 4.9 Studies on COX-1 and COX-2 gene deletion provided some information on the roles 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115790 16647138 150956 17610 9605 PTGS2 COX-2 COX-2 2 16.2 Studies on COX-1 and COX-2 gene deletion provided some information on the roles 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115791 16647138 150956 17610 9605 PTGS2 COX-2 COX-2 4 16.2 Studies on COX-1 and COX-2 gene deletion provided some information on the roles of these 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115792 16647138 150957 4829 2294 COX8A COX COX-1-deficient 25 0.3 reperfusion injury was increased ( Iadecola et al. 2001b in COX-1-deficient mice 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115793 16647138 150959 17609 9604 PTGS1 COX-1 COX-1 11 4.9 were not able to confirm the harmful effect of losing COX-1 activity in a permanent endovascular middle cerebral artery occlusion (MCAO) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115794 16647138 150960 17610 9605 PTGS2 COX COX-2-deficient 0 0.3 COX-2-deficient mice displayed a reduced susceptibility to ischemic brain injury and 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115795 16647138 150961 17610 9605 PTGS2 COX-2 COX-2 6 16.2 Conversely mice with neuronal overexpression of COX-2 had increased levels of PGE 2 with significant increases in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115796 16647138 150962 17610 9605 PTGS2 COX-2 COX-2 9 16.2 Clinical trials have recently revealed that long-term therapy with COX-2 inhibitors increases the incidence of myocardial infarction and stroke which 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115797 16647138 150962 4829 2294 COX8A COX COX-2-derived 30 0.3 has been attributed to blockade of the vasoprotective effects of COX-2-derived PGI 2 ( FitzGerald 2003 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115798 16647138 150962 8612 4458 GPI PGI PGI 31 0.6 been attributed to blockade of the vasoprotective effects of COX-2-derived PGI 2 ( FitzGerald 2003 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000317087492660012<>ScoreDetail__1044|BGN|0.000317087492660012__4458|GPI|0.000299625468164794__ 0 0 0 0 0 115799 16647138 150963 17610 9605 PTGS2 COX-2 COX-2 15 16.2 PGE 2 may be responsible for the neurotoxic effects of COX-2 ( Manabe et al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115800 16647138 150964 17596 9593 PTGER1 EP1 EP1 1 1.2 Prostaglandin EP1 receptors may be essential for the neurotoxic effects of COX-2-derived 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115801 16647138 150964 4829 2294 COX8A COX COX-2-derived 11 0.3 EP1 receptors may be essential for the neurotoxic effects of COX-2-derived PGE 2 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115802 16647138 150965 17596 9593 PTGER1 EP1 EP1 0 1.2 EP1 receptor activation by PGE 2 disrupts neuronal calcium homeostasis by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115803 16647138 150966 17596 9593 PTGER1 EP1 EP1 6 1.2 Pharmacological inhibition or gene inactivation of EP1 receptors reduces brain injury induced by middle cerebral artery occlusion 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115804 16647138 150967 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 mRNA is upregulated in the ischemic rat cerebral hemisphere beginning 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115805 16647138 150968 17610 9605 PTGS2 COX-2 COX-2 10 16.2 Neurons at the medial edge of the ischemic area had COX-2 immunoreactivity and the injured brain had elevated PGE 2 levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115806 16647138 150969 17610 9605 PTGS2 COX-2 COX-2 6 16.2 These data would appear to implicate COX-2 in the mechanisms of delayed neuronal death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115807 16647138 150970 17597 9594 PTGER2 EP2 EP2 7 0.6 However the finding that the PGE 2 EP2 receptor has a neuroprotective function in cerebral ischemia complicates the 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115808 16647138 150972 16459 8893 PGF PGF PGF 4 0.6 Although PGE 2 PGF 2_amp_#x3b1 6-keto-PGF 1_amp_#x3b1 and thromboxanes in the brain extracellular space 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115809 16647138 150989 17609 9604 PTGS1 COX-1 COX-1 19 4.9 PLA 2 activation may be converted to prostaglandins by both COX-1 and COX-2 during the immediate response and predominantly by COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115810 16647138 150989 17610 9605 PTGS2 COX-2 COX-2 19 16.2 PLA 2 activation may be converted to prostaglandins by both COX-1 and COX-2 during the immediate response and predominantly by COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115811 16647138 150989 17610 9605 PTGS2 COX-2 COX-2 21 16.2 activation may be converted to prostaglandins by both COX-1 and COX-2 during the immediate response and predominantly by COX-2 during the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115812 16647138 150989 17610 9605 PTGS2 COX-2 COX-2 29 16.2 COX-1 and COX-2 during the immediate response and predominantly by COX-2 during the delayed response ( Murakami et al. 2002 sPLA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115813 16647138 150989 17610 9605 PTGS2 COX-2 COX-2 43 16.2 delayed response ( Murakami et al. 2002 sPLA 2 upregulates COX-2 ( Bidgood et al. 2000 and is functionally coupled with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115814 16647138 150989 17610 9605 PTGS2 COX-2 COX-2 55 16.2 ( Bidgood et al. 2000 and is functionally coupled with COX-2 but not with COX-1 ( Balsinde et al. 1998 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115815 16647138 150989 17609 9604 PTGS1 COX-1 COX-1 59 4.9 2000 and is functionally coupled with COX-2 but not with COX-1 ( Balsinde et al. 1998 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115816 16647138 150990 17610 9605 PTGS2 COX-2 COX-2 3 16.2 Substantial increases in COX-2 mRNA and protein levels occur in the peri-infarct and focal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115817 16647138 150991 17610 9605 PTGS2 COX-2 COX-2 7 16.2 In the ischemic core significant increases in COX-2 mRNA followed 6 h of ischemia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115818 16647138 150992 17610 9605 PTGS2 COX-2 COX-2 11 16.2 ischemic core during ischemic periods did not show increases in COX-2 protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115819 16647138 150994 17597 9594 PTGER2 EP2 EP2 17 0.6 2 are likely to be important because activation of the EP2 receptor which the cerebral cortex hippocampus and striatum express abundantly 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115820 16647138 150995 17597 9594 PTGER2 EP2 EP2 3 0.6 Pharmacologic blockade of EP2 signaling by blockade of protein kinase A activation reversed this 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115821 16647138 150996 17597 9594 PTGER2 EP2 EP2 9 0.6 In an MCAO mouse model genetic deletion of the EP2 receptor significantly increased cerebral infarction in the cerebral cortex and 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115822 16647138 150998 17609 9604 PTGS1 COX-1 COX-1 4 4.9 In another human study COX-1 expressed intensely in microglia but weakly in neurons in control 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115823 16647138 150998 17610 9605 PTGS2 COX-2 COX-2 17 16.2 in microglia but weakly in neurons in control brains whereas COX-2 was absent in control autopsied brains 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115824 16647138 150999 17610 9605 PTGS2 COX-2 COX-2 1 16.2 However COX-2 was induced robustly in neurons during the acute phase of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115825 16647138 151000 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 was also upregulated in microglia during focal ischemia ( Tomimoto 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115826 16647138 151015 16745 9065 PLCG1 PLC PLC 3 0.6 The phospholipase C (PLC) PLC inhibitor U73122 also failed to depress significantly ischemia/reperfusion ischemia reperfusion 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115827 16647138 151016 16745 9065 PLCG1 PLC PLC 25 0.6 selective inhibitors of sPLA 2 cPLA 2 iPLA 2 and PLC were evaluated for their ability to suppress ischemia/reperfusion-evoked ischemia reperfusion-evoked 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115828 16647138 151017 16745 9065 PLCG1 PLC PLC 3 0.6 This suggests that PLC and several PLA 2 isozymes do contribute to brain injury 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115829 16647138 151019 3353 1368 CA1 CA1 CA1 25 0.0 the generation of the irreversible depolarization induced in hippocampal slice CA1 pyramidal neurons by oxygen/glucose oxygen glucose deprivation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115830 16647138 151020 17610 9605 PTGS2 COX COX 15 2.9 of inhibitors of PLA 2 as well as inhibitors of COX LOX and cytochrome P450 isozymes to reverse the depolarization 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115831 16647138 151020 11934 6664 LOX LOX LOX 16 3.3 inhibitors of PLA 2 as well as inhibitors of COX LOX and cytochrome P450 isozymes to reverse the depolarization 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115832 16647138 151020 5353 2615 CYP2B6 P450 P450 19 2.2 2 as well as inhibitors of COX LOX and cytochrome P450 isozymes to reverse the depolarization 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115833 16647138 151021 5353 2615 CYP2B6 P450 P450 15 2.2 PLA 2 inhibitor 4-bromophenylacyl bromide (pBPB), pBPB or the cytochrome P450 inhibitor 17-octadecynoic acid (17-ODA), 17-ODA significantly restored the membrane potential 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115834 16647138 151025 5353 2615 CYP2B6 P450 P450 35 2.2 to the irreversible depolarization by in vitro ischemia with cytochrome P450 isozymes making a major contribution 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115835 16647138 151027 3353 1368 CA1 CA1 CA1 11 0.0 observed the formation of small blebs on the surface of CA1 pyramidal neurons within 30 s of the rapid depolarization induced 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115836 16647138 151030 17610 9605 PTGS2 COX COX 7 2.9 Numerous studies have evaluated the effects of COX inhibitors on stroke injury 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115837 16647138 151031 17609 9604 PTGS1 COX-1 COX-1 6 4.9 Pretreatment with indomethacin an inhibitor of COX-1 and COX-2 reduced infarct size following focal ischemia with reperfusion 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115838 16647138 151031 17610 9605 PTGS2 COX-2 COX-2 6 16.2 Pretreatment with indomethacin an inhibitor of COX-1 and COX-2 reduced infarct size following focal ischemia with reperfusion 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115839 16647138 151031 17610 9605 PTGS2 COX-2 COX-2 8 16.2 Pretreatment with indomethacin an inhibitor of COX-1 and COX-2 reduced infarct size following focal ischemia with reperfusion in rats 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115840 16647138 151031 3353 1368 CA1 CA1 CA1 27 0.0 reperfusion in rats ( Buccellati et al. 1998 reduced ischemia-evoked CA1 hippocampal injury in a gerbil model ( Sasaki et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115841 16647138 151033 17609 9604 PTGS1 COX-1 COX-1 5 4.9 Ibuprofen which also inhibits both COX-1 and COX-2 reduced neuronal injury and improved cerebral blood flow 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115842 16647138 151033 17610 9605 PTGS2 COX-2 COX-2 5 16.2 Ibuprofen which also inhibits both COX-1 and COX-2 reduced neuronal injury and improved cerebral blood flow 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115843 16647138 151033 17610 9605 PTGS2 COX-2 COX-2 7 16.2 Ibuprofen which also inhibits both COX-1 and COX-2 reduced neuronal injury and improved cerebral blood flow and neurological 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115844 16647138 151034 17610 9605 PTGS2 COX COX 3 2.9 Two other non-selective COX inhibitors piroxicam and flurbiprofen significantly ameliorated delayed (7 7 days 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115845 16647138 151034 3353 1368 CA1 CA1 CA1 18 0.0 ameliorated delayed (7 7 days neuronal deaths in the gerbil CA1 hippocampus 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115846 16647138 151035 3353 1368 CA1 CA1 CA1 13 0.0 study two lipoxygenase inhibitors AA-861 and BW-755C failed to protect CA1 neurons ( Nakagomi et al. 1989 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115847 16647138 151036 17610 9605 PTGS2 COX-2 COX-2 5 16.2 The recent development of selective COX-2 inhibitors has stimulated a number of studies of their efficacy 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115848 16647138 151038 14535 7873 NOS2A NOS NOS 22 2.7 mice with deletion of the inducible nitric oxide synthase (NOS) NOS gene which suggests that COX-2 reaction products may be another 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000487751477192121<>ScoreDetail__7873|NOS2A|0.000487751477192121__7872|NOS1|0.000445308362683434__ 0 0 0 0 0 115849 16647138 151038 17610 9605 PTGS2 COX-2 COX-2 27 16.2 inducible nitric oxide synthase (NOS) NOS gene which suggests that COX-2 reaction products may be another mechanism by which iNOS-derived nitric 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115850 16647138 151038 14535 7873 NOS2A iNOS iNOS-derived 36 2.7 that COX-2 reaction products may be another mechanism by which iNOS-derived nitric oxide contributes to ischemic brain injury ( Nagayama et 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115851 16647138 151040 17610 9605 PTGS2 COX-2 COX-2 1 16.2 Another COX-2 inhibitor nimesulide effectively limited hippocampal damage following forebrain ischemia in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115852 16647138 151041 17610 9605 PTGS2 COX COX-2-deficient 11 0.3 degree of hippocampal neuronal injury produced by global ischemia in COX-2-deficient mice was less than that in wild-type mice ( Sasaki 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115853 16647138 151044 17609 9604 PTGS1 COX-1 COX-1 3 4.9 Selective inhibition of COX-1 by valerylsalicylate or of COX-2 by rofecoxib was used to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115854 16647138 151044 17610 9605 PTGS2 COX-2 COX-2 8 16.2 Selective inhibition of COX-1 by valerylsalicylate or of COX-2 by rofecoxib was used to assess the relative contributions of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115855 16647138 151045 17610 9605 PTGS2 COX COX 26 2.9 was initiated 6 h after ischemia providing evidence that both COX isoforms are involved in the progression of neuronal damage following 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115856 16647138 151045 3353 1368 CA1 CA1 CA1 11 0.0 inhibitors significantly increased the number of healthy neurons in the CA1 hippocampus even when treatment was initiated 6 h after ischemia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115857 16647138 151046 17610 9605 PTGS2 COX-2 COX-2 3 16.2 The highly selective COX-2 inhibitor DFU was neuroprotective when administered several hours after transient 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115858 16647138 151047 17610 9605 PTGS2 COX-2 COX-2 2 16.2 The selective COX-2 inhibitors SC58125 and SC58326 are neuroprotective in rat global and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115859 16647138 151049 17610 9605 PTGS2 COX-2 COX-2 5 16.2 (2004) 2004 examined whether the selective COX-2 inhibitor celecoxib reduces cerebral inflammation and edema after intracerebral hemorrhage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115860 16647138 151053 17610 9605 PTGS2 COX-2 COX-2 5 16.2 S-2474 a novel NSAID suppresses COX-2 at low nanomolar levels but does not affect COX-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115861 16647138 151053 17609 9604 PTGS1 COX-1 COX-1 14 4.9 suppresses COX-2 at low nanomolar levels but does not affect COX-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115862 16647138 151054 926 620 APP amyloid amyloid 8 1.5 It possesses protective effects against the neurotoxicity of _amp_#x3b2 -amyloid protein a protein probably causative in the generation of Alzheimer's 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 115863 16647138 151062 604 435 ALOX5 5-LOX 5-LOX 3 4.7 Neurons immunostaining for 5-LOX were upregulated in sites of focal ischemic damage of human 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115864 16647138 151063 604 435 ALOX5 5-LOX 5-LOX 14 4.7 gerbil brain of 5-min duration led to an upregulation of 5-LOX immunoreactivity in neurons and an increase in LTC 4 in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115865 16647138 151068 3353 1368 CA1 CA1 CA1 10 0.0 The lipoxygenase inhibitors AA-861 and BW-755C failed to protect gerbil CA1 hippocampal neurons from 5 min forebrain ischemia whereas the cyclooxygenase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115866 16647138 151071 11934 6664 LOX LOX LOX 14 3.3 of CA1 pyramidal cells following the application of two non-selective LOX inhibitors nordihydroguaiaretic acid and esculentin a selective 5-LOX inhibitor AA861 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115867 16647138 151071 604 435 ALOX5 5-LOX 5-LOX 22 4.7 two non-selective LOX inhibitors nordihydroguaiaretic acid and esculentin a selective 5-LOX inhibitor AA861 and two selective 12-LOX inhibitors baicalein and cinnamyl-3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115868 16647138 151071 606 429 ALOX12 12-LOX 12-LOX 28 3.1 and esculentin a selective 5-LOX inhibitor AA861 and two selective 12-LOX inhibitors baicalein and cinnamyl-3 4-dihydroxy-_amp_#x3b1 -cyanocinnamate 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115869 16647138 151071 3353 1368 CA1 CA1 CA1 5 0.0 (2001) 2001 demonstrated significant protection of CA1 pyramidal cells following the application of two non-selective LOX inhibitors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115870 16647138 151072 17610 9605 PTGS2 COX COX 1 2.9 Two COX inhibitors indomethacin and ibuprofen were less effective on this preparation 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115871 16647138 151074 604 435 ALOX5 5-LOX 5-LOX 3 4.7 The importance of 5-LOX is further supported by evidence indicating that the gene encoding 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115872 16647138 151074 604 435 ALOX5 5-LOX 5-LOX 14 4.7 is further supported by evidence indicating that the gene encoding 5-LOX activating protein confers a risk of stroke in humans ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115873 16647138 151077 11934 6664 LOX LOX LOX 12 3.3 cultured neurons to arachidonic acid caused apoptotic neuronal death which LOX and CY450 inhibitors greatly reduced with COX inhibitors having less 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115874 16647138 151077 17610 9605 PTGS2 COX COX 19 2.9 neuronal death which LOX and CY450 inhibitors greatly reduced with COX inhibitors having less of an effect 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115875 16647138 151078 604 435 ALOX5 5-LOX 5-LOX 30 4.7 min cerebral ischemia ( Kitagawa et al. 2004 indicating that 5-LOX is not essential for ischemic injury to the brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115876 16647138 151082 5353 2615 CYP2B6 P450 P450 5 2.2 EETs are the only cytochrome P450 metabolites of arachidonic acid produced by endothelial cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115877 16647138 151085 5353 2615 CYP2B6 P450 P450 8 2.2 (2002) 2002 reported that TIA induces the expression of P450 2C11 an arachidonic acid epoxygenase which is upregulated in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115878 16647138 151088 11629 6493 LAMC2 CSF CSF 10 0.0 The levels of 20-HETE a potent vasoconstrictor increase in the CSF of rats ( Kehl et al. 2002 and man ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115879 16647138 151088 203 10522 ACSM3 SAH SAH 33 0.0 Hacein-Bey et al. 2004 and Poloyac et al. 2005 following SAH 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115880 16647138 151090 11629 6493 LAMC2 CSF CSF 42 0.0 rats as well as reversing the increase in 20-HETE in CSF of rats after SAH ( Miyata et al. 2005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115881 16647138 151090 203 10522 ACSM3 SAH SAH 46 0.0 reversing the increase in 20-HETE in CSF of rats after SAH ( Miyata et al. 2005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115882 16647138 151092 17610 9605 PTGS2 COX COX 2 2.9 Role of COX LOX and EPOX in excitotoxic injury 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115883 16647138 151092 11934 6664 LOX LOX LOX 3 3.3 Role of COX LOX and EPOX in excitotoxic injury 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115884 16647138 151092 6701 3401 EPHX1 EPOX EPOX 5 2.9 Role of COX LOX and EPOX in excitotoxic injury 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115885 16647138 151095 9510 17513 HOMER2 ACPD ACPD 22 1.0 -2-amino-4-phosphonobutanoate ( l -AP4 and trans -1-amino-cyclopentyl-1 3-dicarboxylate ( trans -ACPD receptors 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115886 16647138 151095 18187 17922 REPIN1 AP4 AP4 16 0.0 _amp_#x3b1 -amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), AMPA kainate l -2-amino-4-phosphonobutanoate ( l -AP4 and trans -1-amino-cyclopentyl-1 3-dicarboxylate ( trans -ACPD receptors 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115887 16647138 151097 17610 9605 PTGS2 COX-2 COX-2 6 16.2 These enzymes include PLA 2 COX-2 LOX and EPOX 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115888 16647138 151097 11934 6664 LOX LOX LOX 7 3.3 These enzymes include PLA 2 COX-2 LOX and EPOX 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115889 16647138 151097 6701 3401 EPHX1 EPOX EPOX 9 2.9 These enzymes include PLA 2 COX-2 LOX and EPOX 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115890 16647138 151098 17610 9605 PTGS2 COX-2 COX-2 3 16.2 Marked increases in COX-2 and 5-LOX mRNA and protein levels occur following kainate injections 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115891 16647138 151098 604 435 ALOX5 5-LOX 5-LOX 5 4.7 Marked increases in COX-2 and 5-LOX mRNA and protein levels occur following kainate injections in rat 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115892 16647138 151099 17610 9605 PTGS2 COX-2 COX-2 3 16.2 This increase in COX-2 and 5-LOX can be prevented by not only glutamate receptor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115893 16647138 151099 604 435 ALOX5 5-LOX 5-LOX 5 4.7 This increase in COX-2 and 5-LOX can be prevented by not only glutamate receptor antagonists ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115894 16647138 151099 17610 9605 PTGS2 COX-2 COX-2 29 16.2 al. 1999 and Pepicelli et al. 2002 but also by COX-2 and 5-LOX inhibitors ( Manev et al. 2000a and Pepicelli 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115895 16647138 151099 604 435 ALOX5 5-LOX 5-LOX 31 4.7 and Pepicelli et al. 2002 but also by COX-2 and 5-LOX inhibitors ( Manev et al. 2000a and Pepicelli et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115896 16647138 151100 17610 9605 PTGS2 COX-2 COX-2 3 16.2 The role of COX-2 and 5-LOX in excitotoxicity is also supported by microdialysis studies 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115897 16647138 151100 604 435 ALOX5 5-LOX 5-LOX 5 4.7 The role of COX-2 and 5-LOX in excitotoxicity is also supported by microdialysis studies in vivo 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115898 16647138 151101 17609 9604 PTGS1 COX-1 COX-1 18 4.9 blocked by the infusion of NMDA antagonists as well as COX-1 and COX-2 inhibitors indicating that both COX-1 and COX-2 contribute 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115899 16647138 151101 17610 9605 PTGS2 COX-2 COX-2 18 16.2 blocked by the infusion of NMDA antagonists as well as COX-1 and COX-2 inhibitors indicating that both COX-1 and COX-2 contribute 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115900 16647138 151101 17610 9605 PTGS2 COX-2 COX-2 20 16.2 the infusion of NMDA antagonists as well as COX-1 and COX-2 inhibitors indicating that both COX-1 and COX-2 contribute to the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115901 16647138 151101 17609 9604 PTGS1 COX-1 COX-1 25 4.9 as well as COX-1 and COX-2 inhibitors indicating that both COX-1 and COX-2 contribute to the prostaglandin synthesis and oxidative damage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115902 16647138 151101 17610 9605 PTGS2 COX-2 COX-2 25 16.2 as well as COX-1 and COX-2 inhibitors indicating that both COX-1 and COX-2 contribute to the prostaglandin synthesis and oxidative damage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115903 16647138 151101 17610 9605 PTGS2 COX-2 COX-2 27 16.2 as COX-1 and COX-2 inhibitors indicating that both COX-1 and COX-2 contribute to the prostaglandin synthesis and oxidative damage in excitotoxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115904 16647138 151104 17610 9605 PTGS2 COX-2 COX-2 29 16.2 it promotes neuronal injury that depends on the magnitude of COX-2 and 5-LOX expression ( Iadecola et al. 2001a Nakayama et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115905 16647138 151104 604 435 ALOX5 5-LOX 5-LOX 31 4.7 neuronal injury that depends on the magnitude of COX-2 and 5-LOX expression ( Iadecola et al. 2001a Nakayama et al. 1998 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115906 16647138 151105 17610 9605 PTGS2 COX-2 COX-2 5 16.2 It is likely that increased COX-2 and 5-LOX activities and high levels of their reaction products 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115907 16647138 151105 604 435 ALOX5 5-LOX 5-LOX 7 4.7 It is likely that increased COX-2 and 5-LOX activities and high levels of their reaction products are involved 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115908 16647138 151106 6701 3401 EPHX1 EPOX EPOX 9 2.9 Nothing is known about the effect of glutamate on EPOX activity and expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115909 16647138 151107 16745 9065 PLCG1 PLC PLC 13 0.6 reported that G-protein-coupled metabotropic glutamate receptors are functionally linked to PLC and cytochrome P450 arachidonate epoxygenase activity ( Gebremedhin et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115910 16647138 151107 5353 2615 CYP2B6 P450 P450 16 2.2 metabotropic glutamate receptors are functionally linked to PLC and cytochrome P450 arachidonate epoxygenase activity ( Gebremedhin et al. 2003 indicating that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115911 16647138 151107 6701 3401 EPHX1 EPOX EPOX 32 2.9 Gebremedhin et al. 2003 indicating that excitotoxicity may also involve EPOX activity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115912 16647138 151108 17610 9605 PTGS2 COX-2 COX-2 5 16.2 The neurochemical consequences of increased COX-2 and 5-LOX activities and high levels of their products include 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115913 16647138 151108 604 435 ALOX5 5-LOX 5-LOX 7 4.7 The neurochemical consequences of increased COX-2 and 5-LOX activities and high levels of their products include not only 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115914 16647138 151109 17610 9605 PTGS2 COX-2 COX-2 9 16.2 Our emphasis on the interaction between glutamate receptors and COX-2 and 5-LOX activities and their reaction products does not rule 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115915 16647138 151109 604 435 ALOX5 5-LOX 5-LOX 11 4.7 emphasis on the interaction between glutamate receptors and COX-2 and 5-LOX activities and their reaction products does not rule out the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115916 16647138 151110 17610 9605 PTGS2 COX-2 COX-2- 15 2.3 appropriate to apply the concept of synergism between glutamate and COX-2- and 5-LOX-generated products and their receptors to neural cell injury 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115917 16647138 151113 17610 9605 PTGS2 COX-2 COX-2- 6 2.3 The synergistic actions of glutamate and COX-2- and 5-LOX-generated products may be rapid whereas in neurodegenerative disorders 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115918 16647138 151113 17610 9605 PTGS2 COX-2 COX-2- 45 2.3 limited extent due to the availability of ATP glutamate and COX-2- and 5-LOX-product-mediated damage may take a longer time to develop 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115919 16647138 151114 17610 9605 PTGS2 COX-2 COX-2 4 16.2 These studies suggest that COX-2 and 5-LOX-generated products along with free radical formation play critical 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115920 16647138 151116 10676 6121 IRF6 LPS LPS-induced 15 0.3 2 protects hippocampal and cortical neuronal cultures against glutamate-mediated or LPS-induced cytotoxicity ( Akaike et al. 1994 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 115921 16647138 151117 17597 9594 PTGER2 EP2 EP2 21 0.6 and oxygen deprivation is mediated by the activation of an EP2 receptor one of the four PGE 2 receptor subtypes whose 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00313093772779962<>ScoreDetail__9594|PTGER2|0.00313093772779962__14534|SPAG11B|0.000203279577178479__ 0 0 0 0 0 115922 16647138 151123 17610 9605 PTGS2 COX-2 COX-2 26 16.2 of cytosolic PLA 2 ( Kajiwara et al. 1996 and COX-2 ( Marcheselli and Bazan 1996 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115923 16647138 151125 17610 9605 PTGS2 COX-2 COX-2 3 16.2 In rat brain COX-2 mRNA is preferentially expressed in neurons where it is developmentally 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115924 16647138 151125 17610 9605 PTGS2 COX-2 COX-2 22 16.2 it is developmentally regulated ( Tocco et al. 1997 and COX-2 expression is induced by kainic-acid-induced seizures ( Chen et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115925 16647138 151126 17610 9605 PTGS2 COX-2 COX-2 16 16.2 rat cortico-hippocampal neurons is also associated with increased expression of COX-2 ( Tocco et al. 1997 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115926 16647138 151127 17610 9605 PTGS2 COX-2 COX-2 2 16.2 Induction of COX-2 but not COX-1 gene expression has been demonstrated to precede 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115927 16647138 151127 17609 9604 PTGS1 COX-1 COX-1 5 4.9 Induction of COX-2 but not COX-1 gene expression has been demonstrated to precede apoptosis in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115928 16647138 151128 16457 8891 PGD PGD PGD 9 0.3 Spontaneous seizures in gerbils are associated with increases in PGD 2 concentrations in the cerebral cortex hippocampus and striatum and 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 115929 16647138 151130 16459 8893 PGF PGF PGF 4 0.6 The formation of immunoreactive PGF 2_amp_#x3b1 and leukotriene-like activity has been detected in the brains 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115930 16647138 151132 17610 9605 PTGS2 COX COX 23 2.9 ( Birkle and Bazan 1987 indicating the stimulation of both COX and LOX activity 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115931 16647138 151132 11934 6664 LOX LOX LOX 25 3.3 and Bazan 1987 indicating the stimulation of both COX and LOX activity 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115932 16647138 151134 17610 9605 PTGS2 COX-2 COX-2 11 16.2 another seizure model the genetically epilepsy-susceptible E1 mouse expression of COX-2 in the hippocampus was upregulated after an epileptic seizure and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115933 16647138 151134 17610 9605 PTGS2 COX-2 COX-2 24 16.2 hippocampus was upregulated after an epileptic seizure and indomethacin a COX-2 inhibitor shortened the duration from seizure onset to full recovery 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115934 16647138 151135 17610 9605 PTGS2 COX-2 COX-2 11 16.2 rat hippocampal-kindling model enabled a study of the role of COX-2 in seizure activity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115935 16647138 151136 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-2 encoded in an early-response gene increased in a synaptic-activity-dependent manner 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115936 16647138 151137 17610 9605 PTGS2 COX-2 COX-2 10 16.2 When rats were rekindled 34 days later this spreading of COX-2 expression persisted 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115937 16647138 151138 17610 9605 PTGS2 COX-2 COX-2 1 16.2 The COX-2 selective inhibitor nimesulide attenuated kindling development ( Tu and Bazan 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115938 16647138 151138 17610 9605 PTGS2 COX-2 COX-2 16 16.2 attenuated kindling development ( Tu and Bazan 2003 thus neuronal COX-2 gene induction and cPLA 2 activation are key signaling events 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115939 16647138 151140 17610 9605 PTGS2 COX-2 COX-2 5 16.2 (2003) 2003 examined the effects of COX-2 on the _amp_#x2018 rapid kindling_amp_#x2019 development in COX-2 knockout mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115940 16647138 151140 17610 9605 PTGS2 COX-2 COX-2 12 16.2 effects of COX-2 on the _amp_#x2018 rapid kindling_amp_#x2019 development in COX-2 knockout mice and mice treated with nimesulide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115941 16647138 151141 17610 9605 PTGS2 COX-2 COX-2 3 16.2 They also measured COX-2 mRNA expression and PGE 2 concentrations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115942 16647138 151142 17610 9605 PTGS2 COX-2 COX-2 10 16.2 Kindling in hippocampal neurons of control mice markedly increased brain COX-2 mRNA levels with a significant increase in PGE 2 levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115943 16647138 151143 17610 9605 PTGS2 COX-2 COX-2 3 16.2 Moreover conditions of COX-2 deficiency significantly decreased the incidence of after-discharges total after-discharge duration 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115944 16647138 151143 17610 9605 PTGS2 COX-2 COX-2 21 16.2 total after-discharge duration and seizure behavior induction suggesting that inducible COX-2 facilitates the recurrence of hippocampal seizures 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115945 16647138 151145 17610 9605 PTGS2 COX-2 COX-2 12 16.2 a transgenic mouse model with neuronal overexpression of the human COX-2 to further explore its role in excitotoxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115946 16647138 151146 17610 9605 PTGS2 COX-2 hCOX-2 2 2.3 Overexpression of hCOX-2 potentiated the intensity and lethality of kainic acid excitotoxicity thus 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115947 16647138 151146 17610 9605 PTGS2 COX-2 COX-2 19 16.2 acid excitotoxicity thus demonstrating a cause_amp_#x2013 effect relationship between neuronal COX-2 expression and excitotoxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115948 16647138 151147 17610 9605 PTGS2 COX COX 21 2.9 in rats gave further evidence of a neuroprotective effect of COX 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115949 16647138 151149 17610 9605 PTGS2 COX-2 COX-2 1 16.2 The COX-2 selective inhibitor rofecoxib significantly reduced kainate-induced cell death in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115950 16647138 151150 17610 9605 PTGS2 COX-2 COX-2 2 16.2 Another selective COX-2 inhibitor celecoxib was effective in reducing electroshock-induced convulsions in rats 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115951 16647138 151151 17610 9605 PTGS2 COX-2 COX-2 13 16.2 (febrile)-induced febrile -induced seizures no reports on the effects of COX-2 inhibitors on epileptic seizures in humans have appeared 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115952 16647138 151156 926 620 APP amyloid amyloid 5 1.5 The accumulation and aggregation of _amp_#x3b2 -amyloid peptide is believed to be an important event in the 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 115953 16647138 151157 17610 9605 PTGS2 COX COX 3 2.9 The involvement of COX and LOX pathways in AD has been extensively studied in 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115954 16647138 151157 11934 6664 LOX LOX LOX 5 3.3 The involvement of COX and LOX pathways in AD has been extensively studied in brain tissue 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115955 16647138 151157 7708 3811 FOXG1 QIN Qin 39 0.3 2002 Ho et al. 1999 Manev et al. 2000a and Qin et al. 2003 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 115956 16647138 151158 17609 9604 PTGS1 COX-1 COX-1 4 4.9 A marked increase of COX-1 and COX-2 expression and immunoreactivity in cerebral cortex and hippocampal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115957 16647138 151158 17610 9605 PTGS2 COX-2 COX-2 4 16.2 A marked increase of COX-1 and COX-2 expression and immunoreactivity in cerebral cortex and hippocampal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115958 16647138 151158 17610 9605 PTGS2 COX-2 COX-2 6 16.2 A marked increase of COX-1 and COX-2 expression and immunoreactivity in cerebral cortex and hippocampal regions of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115959 16647138 151158 7708 3811 FOXG1 QIN Qin 43 0.3 2 found in AD ( Pasinetti and Aisen 1998 and Qin et al. 2003 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 115960 16647138 151159 17609 9604 PTGS1 COX-1 COX-1 4 4.9 The neuroprotective effects of COX-1 and COX-2 inhibitors (NSAID) NSAID strongly support the view that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115961 16647138 151159 17610 9605 PTGS2 COX-2 COX-2 4 16.2 The neuroprotective effects of COX-1 and COX-2 inhibitors (NSAID) NSAID strongly support the view that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115962 16647138 151159 17610 9605 PTGS2 COX-2 COX-2 6 16.2 The neuroprotective effects of COX-1 and COX-2 inhibitors (NSAID) NSAID strongly support the view that upregulation of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115963 16647138 151160 17609 9604 PTGS1 COX-1 COX-1 5 4.9 The molecular mechanism by which COX-1 and COX-2 promote amyloidogenic accumulation of _amp_#x3b2 -amyloid peptide is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115964 16647138 151160 17610 9605 PTGS2 COX-2 COX-2 5 16.2 The molecular mechanism by which COX-1 and COX-2 promote amyloidogenic accumulation of _amp_#x3b2 -amyloid peptide is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115965 16647138 151160 17610 9605 PTGS2 COX-2 COX-2 7 16.2 The molecular mechanism by which COX-1 and COX-2 promote amyloidogenic accumulation of _amp_#x3b2 -amyloid peptide is not fully 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115966 16647138 151160 926 620 APP amyloid amyloid 12 1.5 by which COX-1 and COX-2 promote amyloidogenic accumulation of _amp_#x3b2 -amyloid peptide is not fully understood 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 115967 16647138 151161 17609 9604 PTGS1 COX-1 COX-1 0 4.9 COX-1 and COX-2 potentiate _amp_#x3b2 -amyloid peptide generation through mechanisms that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115968 16647138 151161 17610 9605 PTGS2 COX-2 COX-2 0 16.2 COX-1 and COX-2 potentiate _amp_#x3b2 -amyloid peptide generation through mechanisms that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115969 16647138 151161 17610 9605 PTGS2 COX-2 COX-2 2 16.2 COX-1 and COX-2 potentiate _amp_#x3b2 -amyloid peptide generation through mechanisms that involve _amp_#x3b3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115970 16647138 151161 926 620 APP amyloid amyloid 4 1.5 COX-1 and COX-2 potentiate _amp_#x3b2 -amyloid peptide generation through mechanisms that involve _amp_#x3b3 -secretase activity ( 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 115971 16647138 151161 7708 3811 FOXG1 QIN Qin 14 0.3 peptide generation through mechanisms that involve _amp_#x3b3 -secretase activity ( Qin et al. 2003 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 115972 16647138 151162 926 620 APP amyloid amyloid 13 1.5 synthesis and _amp_#x3b3 -secretase activity may not only modulate _amp_#x3b2 -amyloid peptide deposition but also induce neuroinflammation in AD brain ( 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 115973 16647138 151163 17610 9605 PTGS2 COX-2 COX-2 1 16.2 Furthermore COX-2 expression is also involved in regulation of cell cycle activity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115974 16647138 151164 17610 9605 PTGS2 COX-2 COX-2-mediated 7 2.3 Re-entry into the cell cycle may underlie COX-2-mediated neuronal damage in AD ( Xiang et al. 2002 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115975 16647138 151165 604 435 ALOX5 5-LOX 5-LOX 2 4.7 Upregulation of 5-LOX expression has also been reported to occur in various regions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115976 16647138 151167 604 435 ALOX5 5-LOX 5-LOX 3 4.7 The significance of 5-LOX upregulation in aged rat brain remains unknown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115977 16647138 151168 604 435 ALOX5 5-LOX 5-LOX 2 4.7 However increased 5-LOX activity may make neurons vulnerable to various insults including excitotoxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115978 16647138 151169 604 435 ALOX5 5-LOX 5-LOX 4 4.7 Based on these findings 5-LOX gene polymorphism has been proposed for the onset of AD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115979 16647138 151170 6701 3401 EPHX1 EPOX EPOX 7 2.9 At present no information is available on EPOX activity and expression in AD brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115980 16647138 151171 11934 6664 LOX LOX LOX 14 3.3 indicate that arachidonic-acid-mediated neuronal death can be prevented by the LOX inhibitors nordihydroguaiaretic acid AA861 and baicalein and the EPOX inhibitors 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115981 16647138 151171 6701 3401 EPHX1 EPOX EPOX 23 2.9 the LOX inhibitors nordihydroguaiaretic acid AA861 and baicalein and the EPOX inhibitors SKF25A and metyrapone but not by the COX inhibitors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115982 16647138 151171 17610 9605 PTGS2 COX COX 32 2.9 the EPOX inhibitors SKF25A and metyrapone but not by the COX inhibitors indomethacin and NS-398 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 115983 16647138 151172 11934 6664 LOX LOX LOX 3 3.3 This suggests that LOX and EPOX pathways may also be involved in LOX- and 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115984 16647138 151172 6701 3401 EPHX1 EPOX EPOX 5 2.9 This suggests that LOX and EPOX pathways may also be involved in LOX- and EPOX-generated metabolite-induced 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115985 16647138 151172 6701 3401 EPHX1 EPOX EPOX-generated 14 1.6 and EPOX pathways may also be involved in LOX- and EPOX-generated metabolite-induced neurodegeneration ( Kwon et al. 2005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115986 16647138 151172 11934 6664 LOX LOX LOX- 12 0.1 that LOX and EPOX pathways may also be involved in LOX- and EPOX-generated metabolite-induced neurodegeneration ( Kwon et al. 2005 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115987 16647138 151173 11934 6664 LOX LOX LOX 4 3.3 The neuroprotective effects of LOX and EPOX inhibitors may relate to downregulation of free radical 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115988 16647138 151173 6701 3401 EPHX1 EPOX EPOX 6 2.9 The neuroprotective effects of LOX and EPOX inhibitors may relate to downregulation of free radical formation under 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115989 16647138 151175 20996 11179 SOD1 ALS ALS 3 2.9 Amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 115990 16647138 151176 20996 11179 SOD1 ALS ALS 0 2.9 ALS is a neurological disease that damages motor neurons in the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 115991 16647138 151177 20996 11179 SOD1 ALS ALS 5 2.9 Although the primary cause of ALS is unknown excitotoxic and oxidative cross talk between motor neurons 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 115992 16647138 151177 20996 11179 SOD1 ALS ALS 27 2.9 surrounding glial cells may be involved in the pathogenesis of ALS ( Rao and Weiss 2004 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 115993 16647138 151177 832 549 AOC2 RAO Rao 29 0.3 cells may be involved in the pathogenesis of ALS ( Rao and Weiss 2004 2 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 115994 16647138 151182 20996 11179 SOD1 ALS ALS 3 2.9 Most cases of ALS are sporadic but 10% are familial 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 115995 16647138 151183 17610 9605 PTGS2 COX-2 COX-2 15 16.2 disease is characterized by a prominent neuroinflammatory component upregulation of COX-2 mRNA and oxidative stress ( Yasojima et al. 2001 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115996 16647138 151184 20996 11179 SOD1 SOD1 SOD1 5 2.9 Mutations in Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 gene have been reported to occur in familial form of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115997 16647138 151184 20996 11179 SOD1 ALS ALS 16 2.9 gene have been reported to occur in familial form of ALS ( Beal 1998a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 115998 16647138 151185 17610 9605 PTGS2 COX-2 COX-2 2 16.2 Upregulation of COX-2 mRNA also occurs in SOD1 transgenic mice at the onset 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 115999 16647138 151185 20996 11179 SOD1 SOD1 SOD1 7 2.9 Upregulation of COX-2 mRNA also occurs in SOD1 transgenic mice at the onset of ALS ( Almer et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116000 16647138 151185 20996 11179 SOD1 ALS ALS 14 2.9 also occurs in SOD1 transgenic mice at the onset of ALS ( Almer et al. 2001 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 116001 16647138 151186 20996 11179 SOD1 SOD1 SOD1 7 2.9 It is not known why mutations of SOD1 are related to the antioxidant activity that leads to ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116002 16647138 151186 20996 11179 SOD1 ALS ALS 17 2.9 SOD1 are related to the antioxidant activity that leads to ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 116003 16647138 151187 20996 11179 SOD1 ALS ALS 7 2.9 In an organotypic cell culture model of ALS the addition of a selective COX-2 inhibitor SC236 blocked the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 116004 16647138 151187 17610 9605 PTGS2 COX-2 COX-2 13 16.2 cell culture model of ALS the addition of a selective COX-2 inhibitor SC236 blocked the destruction of motor neurons ( Drachman 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116005 16647138 151187 17610 9605 PTGS2 COX-2 COX-2 30 16.2 of motor neurons ( Drachman and Rothstein 2000 suggesting that COX-2 may play an important role in inflammatory processes in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116006 16647138 151187 20996 11179 SOD1 ALS ALS 40 2.9 COX-2 may play an important role in inflammatory processes in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 116007 16647138 151188 17610 9605 PTGS2 COX-2 COX-2 5 16.2 Similarly treatment with celecoxib another COX-2 inhibitor prolongs the survival of neurons in the SOD1 mouse 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116008 16647138 151188 20996 11179 SOD1 SOD1 SOD1 14 2.9 another COX-2 inhibitor prolongs the survival of neurons in the SOD1 mouse model of ALS ( Drachman et al. 2002 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116009 16647138 151188 20996 11179 SOD1 ALS ALS 18 2.9 the survival of neurons in the SOD1 mouse model of ALS ( Drachman et al. 2002 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 116010 16647138 151189 17610 9605 PTGS2 COX-2 COX-2 3 16.2 Although upregulation of COX-2 and PGE 2 levels may not be the root cause 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116011 16647138 151189 20996 11179 SOD1 ALS ALS 15 2.9 PGE 2 levels may not be the root cause of ALS alterations in these parameters may be responsible for the induction 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 116012 16647138 151189 20996 11179 SOD1 ALS ALS 34 2.9 the induction and maintenance of inflammation during the progression of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 116013 16647138 151190 11934 6664 LOX LOX LOX 4 3.3 At present information on LOX and EPOX expression and their activities is not available for 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116014 16647138 151190 6701 3401 EPHX1 EPOX EPOX 6 2.9 At present information on LOX and EPOX expression and their activities is not available for the ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116015 16647138 151190 20996 11179 SOD1 ALS ALS 16 2.9 EPOX expression and their activities is not available for the ALS brain and spinal cord 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 116016 16647138 151194 20996 11179 SOD1 SOD SOD 12 2.9 has increased lipid peroxidation iron levels and superoxide dismutase (SOD) SOD activity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116017 16647138 151196 17610 9605 PTGS2 COX-2 COX-2 9 16.2 At present nothing is known about the expression of COX-2 in patients with PD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116018 16647138 151197 17610 9605 PTGS2 COX-2 COX-2 3 16.2 However involvement of COX-2 in the pathogenesis of PD has been explored in an 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116019 16647138 151197 17610 9605 PTGS2 COX-2 COX-2 26 16.2 2 3 6 tetrahydropyridine (MPTP) MPTP as well as in COX-2 gene knockout mice ( Feng et al. 2003 and Teismann 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116020 16647138 151198 17610 9605 PTGS2 COX COX-2-deficient 13 0.3 mortality rate has been reported after MPTP injection in heterozygous COX-2-deficient mice than in the wild-type mice and inhibition of COX-2 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116021 16647138 151198 17610 9605 PTGS2 COX-2 COX-2 23 16.2 COX-2-deficient mice than in the wild-type mice and inhibition of COX-2 protein expression decreases the lesions caused by MPTP and protects 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116022 16647138 151199 17610 9605 PTGS2 COX-2 COX-2-mediated 5 2.3 The molecular mechanism associated with COX-2-mediated neurodegeneration in animal models of PD remains unknown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116023 16647138 151200 17610 9605 PTGS2 COX-2 COX-2 1 16.2 However COX-2 inhibition may prevent the formation of the oxidant species of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116024 16647138 151202 11934 6664 LOX LOX LOX 5 3.3 No information is available on LOX and EPOX expression and activities in PD brains 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116025 16647138 151202 6701 3401 EPHX1 EPOX EPOX 7 2.9 No information is available on LOX and EPOX expression and activities in PD brains 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116026 16647138 151203 11934 6664 LOX LOX LOX 3 3.3 The involvement of LOX and EPOX in the pathogenesis of PD has been studied 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116027 16647138 151203 6701 3401 EPHX1 EPOX EPOX 5 2.9 The involvement of LOX and EPOX in the pathogenesis of PD has been studied in glutathione 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116028 16647138 151204 606 429 ALOX12 12-LOX 12-LOX 9 3.1 A decrease in GSH triggers the activation of neuronal 12-LOX resulting in the production of 12-LOX-generated products and peroxides ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116029 16647138 151205 606 429 ALOX12 12-LOX 12-LOX 5 3.1 Treatment of cell cultures with 12-LOX inhibitors blocks neuronal cell death induced by GSH depletion 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116030 16647138 151206 11934 6664 LOX LOX LOX 4 3.3 This suggests that a LOX pathway is associated with neuronal degeneration in PD 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116031 16647138 151207 6701 3401 EPHX1 EPOX EPOX 2 2.9 Involvement of EPOX in the pathogenesis of PD has also been studied 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116032 16647138 151209 17610 9605 PTGS2 COX COX 6 2.9 Collective evidence suggests that changes in COX LOX and EPOX activities may not be the primary effect 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116033 16647138 151209 11934 6664 LOX LOX LOX 7 3.3 Collective evidence suggests that changes in COX LOX and EPOX activities may not be the primary effect but 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116034 16647138 151209 6701 3401 EPHX1 EPOX EPOX 9 2.9 Collective evidence suggests that changes in COX LOX and EPOX activities may not be the primary effect but a secondary 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116035 16647138 151211 17345 9449 PRNP CJD CJD 2 1.1 Creutzfeldt_amp_#x2013 Jakob disease (CJD) CJD 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116036 16647138 151212 17345 9449 PRNP CJD CJD 0 1.1 CJD is the most prevalent form of prion disease in humans 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116037 16647138 151213 17345 9449 PRNP PrP PrP 12 1.1 accumulation of abnormal extracellular _amp_#x3b2 -helix rich prion protein (PrP PrP sc characterize CJD 1 JUMiner_v2.2 1 0 0 2 9353 TotalCon:4<>9353|PRDX2|7001|Complete__9449|PRNP|5621|Complete__47|ABCB6|10058|Complete__1325|C4BPA|722|Complete__<>AvaiableGeneRif=4<>BEST:9353|PRDX2|0.000725335546199934<>ScoreDetail__1325|C4BPA|0.00035801836055732__47|ABCB6|0.000342905503998132__9353|PRDX2|0.000725335546199934__9449|PRNP|0.000367144007841125__ 0 0 0 0 0 116038 16647138 151213 17345 9449 PRNP CJD CJD 16 1.1 extracellular _amp_#x3b2 -helix rich prion protein (PrP PrP sc characterize CJD 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116039 16647138 151214 17345 9449 PRNP PrP PrP 13 1.1 isoform of a normally occurring _amp_#x3b1 -helix-rich prion protein (PrP PrP c whose function has not been clearly elucidated ( Brown 1 JUMiner_v2.2 1 0 0 2 9353 TotalCon:4<>9353|PRDX2|7001|Complete__9449|PRNP|5621|Complete__47|ABCB6|10058|Complete__1325|C4BPA|722|Complete__<>AvaiableGeneRif=4<>BEST:9353|PRDX2|0.000725335546199934<>ScoreDetail__1325|C4BPA|0.00035801836055732__47|ABCB6|0.000342905503998132__9353|PRDX2|0.000725335546199934__9449|PRNP|0.000367144007841125__ 0 0 0 0 0 116040 16647138 151215 17345 9449 PRNP PrP PrP 4 1.1 It is proposed that PrP c is associated with synaptic function circadian rhythms regulation and 1 JUMiner_v2.2 1 0 0 2 9353 TotalCon:4<>9353|PRDX2|7001|Complete__9449|PRNP|5621|Complete__47|ABCB6|10058|Complete__1325|C4BPA|722|Complete__<>AvaiableGeneRif=4<>BEST:9353|PRDX2|0.000725335546199934<>ScoreDetail__1325|C4BPA|0.00035801836055732__47|ABCB6|0.000342905503998132__9353|PRDX2|0.000725335546199934__9449|PRNP|0.000367144007841125__ 0 0 0 0 0 116041 16647138 151217 17345 9449 PRNP PrP PrP 3 1.1 The observation that PrP c regulates Cu 2 /Zn Zn 2 superoxide dismutase suggests 1 JUMiner_v2.2 1 0 0 2 9353 TotalCon:4<>9353|PRDX2|7001|Complete__9449|PRNP|5621|Complete__47|ABCB6|10058|Complete__1325|C4BPA|722|Complete__<>AvaiableGeneRif=4<>BEST:9353|PRDX2|0.000725335546199934<>ScoreDetail__1325|C4BPA|0.00035801836055732__47|ABCB6|0.000342905503998132__9353|PRDX2|0.000725335546199934__9449|PRNP|0.000367144007841125__ 0 0 0 0 0 116042 16647138 151217 17345 9449 PRNP PrP PrP 14 1.1 regulates Cu 2 /Zn Zn 2 superoxide dismutase suggests that PrP c is involved in redox balance 1 JUMiner_v2.2 1 0 0 2 9353 TotalCon:4<>9353|PRDX2|7001|Complete__9449|PRNP|5621|Complete__47|ABCB6|10058|Complete__1325|C4BPA|722|Complete__<>AvaiableGeneRif=4<>BEST:9353|PRDX2|0.000725335546199934<>ScoreDetail__1325|C4BPA|0.00035801836055732__47|ABCB6|0.000342905503998132__9353|PRDX2|0.000725335546199934__9449|PRNP|0.000367144007841125__ 0 0 0 0 0 116043 16647138 151218 17345 9449 PRNP CJD CJD 17 1.1 oxidative stress may be closely associated with the pathogenesis of CJD ( Capellari et al. 1999 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116044 16647138 151219 17609 9604 PTGS1 COX-1 COX-1 6 4.9 Using RT-PCR and Western blotting both COX-1 and COX-2 are significantly increased in brains from CJD patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116045 16647138 151219 17610 9605 PTGS2 COX-2 COX-2 6 16.2 Using RT-PCR and Western blotting both COX-1 and COX-2 are significantly increased in brains from CJD patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116046 16647138 151219 17610 9605 PTGS2 COX-2 COX-2 8 16.2 Using RT-PCR and Western blotting both COX-1 and COX-2 are significantly increased in brains from CJD patients compared to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116047 16647138 151219 17345 9449 PRNP CJD CJD 15 1.1 both COX-1 and COX-2 are significantly increased in brains from CJD patients compared to age-matched controls implicating both enzymes in the 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116048 16647138 151219 17345 9449 PRNP CJD CJD 28 1.1 to age-matched controls implicating both enzymes in the pathogenesis of CJD ( Deininger et al. 2003 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116049 16647138 151220 17345 9449 PRNP CJD CJD 6 1.1 In CSF from sporadic and familial CJD and in brain homogenates of scrapie-infected mice the upregulation of 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116050 16647138 151220 17609 9604 PTGS1 COX-1 COX-1 17 4.9 and in brain homogenates of scrapie-infected mice the upregulation of COX-1 and COX-2 is accompanied by a several-fold increase in concentrations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116051 16647138 151220 17610 9605 PTGS2 COX-2 COX-2 17 16.2 and in brain homogenates of scrapie-infected mice the upregulation of COX-1 and COX-2 is accompanied by a several-fold increase in concentrations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116052 16647138 151220 17610 9605 PTGS2 COX-2 COX-2 19 16.2 brain homogenates of scrapie-infected mice the upregulation of COX-1 and COX-2 is accompanied by a several-fold increase in concentrations of PGE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116053 16647138 151220 11629 6493 LAMC2 CSF CSF 1 0.0 In CSF from sporadic and familial CJD and in brain homogenates of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116054 16647138 151221 17345 9449 PRNP CJD CJD 12 1.1 on PGE 2 levels have been obtained in CSF of CJD variants ( Minghetti et al. 2002 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116055 16647138 151221 11629 6493 LAMC2 CSF CSF 10 0.1 Similar results on PGE 2 levels have been obtained in CSF of CJD variants ( Minghetti et al. 2002 6 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 116056 16647138 151222 17345 9449 PRNP CJD CJD 17 1.1 participate in the inflammatory process and have a role in CJD pathogenesis 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116057 16647138 151223 17345 9449 PRNP CJD CJD 17 1.1 death or is itself a consequence of neuronal disturbance in CJD remains to be defined 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116058 16647138 151229 604 435 ALOX5 5-LOX 5-LOX 1 4.7 The 5-LOX pathway may mediate the PrP106_amp_#x2013 126 toxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116059 16647138 151230 604 435 ALOX5 5-LOX 5-LOX 14 4.7 the observation that PrP106_amp_#x2013 126-mediated neurodegeneration can be blocked by 5-LOX inhibitors such as nordihydroguaiaretic acid and caffeic acid 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116060 16647138 151231 604 435 ALOX5 5-LOX 5-LOX-mediated 14 1.6 PrP106_amp_#x2013 126-induced caspase-3 activation and annexin V binding involved in 5-LOX-mediated apoptosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116061 16647138 151232 17609 9604 PTGS1 COX-1 COX-1 4 4.9 In contrast indomethacin a COX-1 and COX-2 inhibitor and baicalein a 12-LOX inhibitor do not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116062 16647138 151232 17610 9605 PTGS2 COX-2 COX-2 4 16.2 In contrast indomethacin a COX-1 and COX-2 inhibitor and baicalein a 12-LOX inhibitor do not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116063 16647138 151232 17610 9605 PTGS2 COX-2 COX-2 6 16.2 In contrast indomethacin a COX-1 and COX-2 inhibitor and baicalein a 12-LOX inhibitor do not affect PrP106_amp_#x2013 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116064 16647138 151232 606 429 ALOX12 12-LOX 12-LOX 11 3.1 contrast indomethacin a COX-1 and COX-2 inhibitor and baicalein a 12-LOX inhibitor do not affect PrP106_amp_#x2013 126-induced neurotoxicity in cerebellar granule 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116065 16647138 151233 604 435 ALOX5 5-LOX 5-LOX 3 4.7 These observations implicate 5-LOX in the pathophysiology of CJD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116066 16647138 151233 17345 9449 PRNP CJD CJD 8 1.1 These observations implicate 5-LOX in the pathophysiology of CJD 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116067 16647138 151234 6701 3401 EPHX1 EPOX EPOX 5 2.9 Information on the involvement of EPOX in CJD is not available 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116068 16647138 151234 17345 9449 PRNP CJD CJD 7 1.1 Information on the involvement of EPOX in CJD is not available 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116069 16647138 151236 17610 9605 PTGS2 COX COX 7 2.9 Future perspectives interactions among multiple forms of COX LOX and EPOX and their relationship to upstream PLA 2 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116070 16647138 151236 11934 6664 LOX LOX LOX 8 3.3 Future perspectives interactions among multiple forms of COX LOX and EPOX and their relationship to upstream PLA 2 isoforms 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116071 16647138 151236 6701 3401 EPHX1 EPOX EPOX 10 2.9 Future perspectives interactions among multiple forms of COX LOX and EPOX and their relationship to upstream PLA 2 isoforms and downstream 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116072 16647138 151237 17610 9605 PTGS2 COX COX 7 2.9 Although transcripts activities and immunoreactive proteins for COX LOX and EPOX are widely expressed throughout the brain very 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116073 16647138 151237 11934 6664 LOX LOX LOX 8 3.3 Although transcripts activities and immunoreactive proteins for COX LOX and EPOX are widely expressed throughout the brain very little 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116074 16647138 151237 6701 3401 EPHX1 EPOX EPOX 10 2.9 Although transcripts activities and immunoreactive proteins for COX LOX and EPOX are widely expressed throughout the brain very little is known 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116075 16647138 151238 17610 9605 PTGS2 COX COX 5 2.9 The occurrence of isoforms of COX LOX and EPOX enzymes in cytoplasm and other subcellular organelles 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116076 16647138 151238 11934 6664 LOX LOX LOX 6 3.3 The occurrence of isoforms of COX LOX and EPOX enzymes in cytoplasm and other subcellular organelles (plasma 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116077 16647138 151238 6701 3401 EPHX1 EPOX EPOX 8 2.9 The occurrence of isoforms of COX LOX and EPOX enzymes in cytoplasm and other subcellular organelles (plasma plasma and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116078 16647138 151239 17610 9605 PTGS2 COX COX 3 2.9 The multiplicity of COX LOX and EPOX enzymes in brain tissue provides diversity in 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116079 16647138 151239 11934 6664 LOX LOX LOX 4 3.3 The multiplicity of COX LOX and EPOX enzymes in brain tissue provides diversity in their 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116080 16647138 151239 6701 3401 EPHX1 EPOX EPOX 6 2.9 The multiplicity of COX LOX and EPOX enzymes in brain tissue provides diversity in their function and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116081 16647138 151241 17609 9604 PTGS1 COX-1 COX-1 4 4.9 In astrocytes TGF_amp_#x3b2 1 upregulates COX-1 expression and serum increases COX-2 expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116082 16647138 151241 17610 9605 PTGS2 COX-2 COX-2 9 16.2 In astrocytes TGF_amp_#x3b2 1 upregulates COX-1 expression and serum increases COX-2 expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116083 16647138 151242 17609 9604 PTGS1 COX-1 COX-1 5 4.9 Neither TGF_amp_#x3b2 1 nor serum affects COX-1 and COX-2 expression in neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116084 16647138 151242 17610 9605 PTGS2 COX-2 COX-2 5 16.2 Neither TGF_amp_#x3b2 1 nor serum affects COX-1 and COX-2 expression in neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116085 16647138 151242 17610 9605 PTGS2 COX-2 COX-2 7 16.2 Neither TGF_amp_#x3b2 1 nor serum affects COX-1 and COX-2 expression in neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116086 16647138 151243 17609 9604 PTGS1 COX-1 COX-1 1 4.9 Furthermore COX-1 compensates for the loss of COX-2 in the COX-2 knockout 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116087 16647138 151243 17610 9605 PTGS2 COX-2 COX-2 7 16.2 Furthermore COX-1 compensates for the loss of COX-2 in the COX-2 knockout (COX-2 COX-2 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 mouse 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116088 16647138 151243 17610 9605 PTGS2 COX-2 COX-2 10 16.2 Furthermore COX-1 compensates for the loss of COX-2 in the COX-2 knockout (COX-2 COX-2 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 mouse brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116089 16647138 151243 17610 9605 PTGS2 COX-2 COX-2 12 16.2 for the loss of COX-2 in the COX-2 knockout (COX-2 COX-2 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 mouse brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116090 16647138 151244 17610 9605 PTGS2 COX-2 COX-2 1 16.2 Thus COX-2 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 shows a compensatory increase in brain COX-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116091 16647138 151244 17609 9604 PTGS1 COX-1 COX-1 9 4.9 COX-2 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 shows a compensatory increase in brain COX-1 expression and activity (with with exogenous arachidonic acid in brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116092 16647138 151245 604 435 ALOX5 5-LOX 5-LOX 4 4.7 Similarly neuronal and astrocytic 5-LOX 12-LOX and 15-LOX and EPOX isozymes differ considerably in responses 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116093 16647138 151245 606 429 ALOX12 12-LOX 12-LOX 5 3.1 Similarly neuronal and astrocytic 5-LOX 12-LOX and 15-LOX and EPOX isozymes differ considerably in responses to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116094 16647138 151245 6701 3401 EPHX1 EPOX EPOX 9 2.9 Similarly neuronal and astrocytic 5-LOX 12-LOX and 15-LOX and EPOX isozymes differ considerably in responses to exogenous stimuli ( Funk 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116095 16647138 151246 17610 9605 PTGS2 COX COX 6 2.9 This behavior complicates the analysis of COX LOX and EPOX function at cellular and subcellular levels 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116096 16647138 151246 11934 6664 LOX LOX LOX 7 3.3 This behavior complicates the analysis of COX LOX and EPOX function at cellular and subcellular levels 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116097 16647138 151246 6701 3401 EPHX1 EPOX EPOX 9 2.9 This behavior complicates the analysis of COX LOX and EPOX function at cellular and subcellular levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116098 16647138 151247 17610 9605 PTGS2 COX COX 17 2.9 when one considers the coupling mechanisms of various isoforms of COX LOX and EPOX with different receptors at cellular and subcellular 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116099 16647138 151247 11934 6664 LOX LOX LOX 18 3.3 one considers the coupling mechanisms of various isoforms of COX LOX and EPOX with different receptors at cellular and subcellular levels 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116100 16647138 151247 6701 3401 EPHX1 EPOX EPOX 20 2.9 the coupling mechanisms of various isoforms of COX LOX and EPOX with different receptors at cellular and subcellular levels and tries 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116101 16647138 151248 17610 9605 PTGS2 COX COX 3 2.9 Some isoforms of COX LOX and EPOX are constitutively expressed while others are inducible 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116102 16647138 151248 11934 6664 LOX LOX LOX 4 3.3 Some isoforms of COX LOX and EPOX are constitutively expressed while others are inducible in 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116103 16647138 151248 6701 3401 EPHX1 EPOX EPOX 6 2.9 Some isoforms of COX LOX and EPOX are constitutively expressed while others are inducible in response to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116104 16647138 151249 17610 9605 PTGS2 COX COX 3 2.9 The isoforms of COX LOX and EPOX may not function interchangeably but act in 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116105 16647138 151249 11934 6664 LOX LOX LOX 4 3.3 The isoforms of COX LOX and EPOX may not function interchangeably but act in parallel 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116106 16647138 151249 6701 3401 EPHX1 EPOX EPOX 6 2.9 The isoforms of COX LOX and EPOX may not function interchangeably but act in parallel to transducer 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116107 16647138 151250 17610 9605 PTGS2 COX COX 7 2.9 It is likely that various isoforms of COX LOX and EPOX act on different cellular pools of arachidonic 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116108 16647138 151250 11934 6664 LOX LOX LOX 8 3.3 It is likely that various isoforms of COX LOX and EPOX act on different cellular pools of arachidonic acid 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116109 16647138 151250 6701 3401 EPHX1 EPOX EPOX 10 2.9 It is likely that various isoforms of COX LOX and EPOX act on different cellular pools of arachidonic acid located in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116110 16647138 151253 17610 9605 PTGS2 COX COX 4 2.9 Thus the interactions among COX LOX and EPOX-generated metabolites at plasma membrane cytoplasmic and nuclear 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116111 16647138 151253 11934 6664 LOX LOX LOX 5 3.3 Thus the interactions among COX LOX and EPOX-generated metabolites at plasma membrane cytoplasmic and nuclear membrane 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116112 16647138 151253 6701 3401 EPHX1 EPOX EPOX-generated 7 1.6 Thus the interactions among COX LOX and EPOX-generated metabolites at plasma membrane cytoplasmic and nuclear membrane levels may 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116113 16647138 151254 17610 9605 PTGS2 COX COX 12 2.9 tempting to speculate that coordinated cross talk not only among COX LOX and EPOX isozymes but also with upstream PLA 2 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116114 16647138 151254 11934 6664 LOX LOX LOX 13 3.3 to speculate that coordinated cross talk not only among COX LOX and EPOX isozymes but also with upstream PLA 2 isozymes 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116115 16647138 151254 6701 3401 EPHX1 EPOX EPOX 15 2.9 that coordinated cross talk not only among COX LOX and EPOX isozymes but also with upstream PLA 2 isozymes and downstream 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116116 16647138 151255 17610 9605 PTGS2 COX COX 6 2.9 In the nuclear membrane and nucleus COX LOX and EPOX-mediated signaling has the advantage over plasma membrane 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116117 16647138 151255 11934 6664 LOX LOX LOX 7 3.3 In the nuclear membrane and nucleus COX LOX and EPOX-mediated signaling has the advantage over plasma membrane signaling 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116118 16647138 151255 6701 3401 EPHX1 EPOX EPOX-mediated 9 1.6 In the nuclear membrane and nucleus COX LOX and EPOX-mediated signaling has the advantage over plasma membrane signaling in that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116119 16647138 151256 17610 9605 PTGS2 COX COX 6 2.9 In brain tissue the activities of COX LOX and EPOX isoforms may depend not only on the 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116120 16647138 151256 11934 6664 LOX LOX LOX 7 3.3 In brain tissue the activities of COX LOX and EPOX isoforms may depend not only on the structural 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116121 16647138 151256 6701 3401 EPHX1 EPOX EPOX 9 2.9 In brain tissue the activities of COX LOX and EPOX isoforms may depend not only on the structural physico-chemical and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116122 16647138 151257 17610 9605 PTGS2 COX COX 3 2.9 The ability of COX LOX and EPOX isoforms to orchestrate complex prostaglandin leukotriene HETE 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116123 16647138 151257 11934 6664 LOX LOX LOX 4 3.3 The ability of COX LOX and EPOX isoforms to orchestrate complex prostaglandin leukotriene HETE and 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116124 16647138 151257 6701 3401 EPHX1 EPOX EPOX 6 2.9 The ability of COX LOX and EPOX isoforms to orchestrate complex prostaglandin leukotriene HETE and EET-mediated physiologic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116125 16647138 151258 17610 9605 PTGS2 COX COX 3 2.9 The activation of COX LOX and EPOX isoforms at a subcellular level in neural 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116126 16647138 151258 11934 6664 LOX LOX LOX 4 3.3 The activation of COX LOX and EPOX isoforms at a subcellular level in neural cells 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116127 16647138 151258 6701 3401 EPHX1 EPOX EPOX 6 2.9 The activation of COX LOX and EPOX isoforms at a subcellular level in neural cells is the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116128 16647138 151259 17610 9605 PTGS2 COX COX 5 2.9 Therefore a strict regulation of COX LOX and EPOX isozymes is very important for normal brain 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116129 16647138 151259 11934 6664 LOX LOX LOX 6 3.3 Therefore a strict regulation of COX LOX and EPOX isozymes is very important for normal brain function 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116130 16647138 151259 6701 3401 EPHX1 EPOX EPOX 8 2.9 Therefore a strict regulation of COX LOX and EPOX isozymes is very important for normal brain function 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116131 16647138 151260 17610 9605 PTGS2 COX COX 6 2.9 As stated above the regulation of COX LOX and EPOX activities is complex and mediated by several 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116132 16647138 151260 11934 6664 LOX LOX LOX 7 3.3 As stated above the regulation of COX LOX and EPOX activities is complex and mediated by several factors 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116133 16647138 151260 6701 3401 EPHX1 EPOX EPOX 9 2.9 As stated above the regulation of COX LOX and EPOX activities is complex and mediated by several factors including translocation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116134 16647138 151261 17610 9605 PTGS2 COX COX 7 2.9 To understand the contribution of isoforms of COX LOX and EPOX in physiological and disease processes a systematic 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116135 16647138 151261 11934 6664 LOX LOX LOX 8 3.3 To understand the contribution of isoforms of COX LOX and EPOX in physiological and disease processes a systematic approach 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116136 16647138 151261 6701 3401 EPHX1 EPOX EPOX 10 2.9 To understand the contribution of isoforms of COX LOX and EPOX in physiological and disease processes a systematic approach will be 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116137 16647138 151266 17610 9605 PTGS2 COX COX 6 2.9 The enzymic mechanisms include three systems COX isozymes which synthesize prostaglandins LOX isozymes which generate hydroxyl derivatives 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116138 16647138 151266 11934 6664 LOX LOX LOX 11 3.3 enzymic mechanisms include three systems COX isozymes which synthesize prostaglandins LOX isozymes which generate hydroxyl derivatives and leukotrienes and EPOX isozymes 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116139 16647138 151266 6701 3401 EPHX1 EPOX EPOX 20 2.9 prostaglandins LOX isozymes which generate hydroxyl derivatives and leukotrienes and EPOX isozymes which produce epoxyeicosatrienoic products 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116140 16647138 151272 20996 11179 SOD1 ALS ALS 11 2.9 pathological situations such as acute neural trauma ischemia AD PD ALS and CJD stimulation and upregulation of COX LOX and EPOX 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00148225451265134<>ScoreDetail__5468|IGFALS|0.0003272086584445__11179|SOD1|0.00148225451265134__ 0 0 0 0 0 116141 16647138 151272 17345 9449 PRNP CJD CJD 13 1.1 such as acute neural trauma ischemia AD PD ALS and CJD stimulation and upregulation of COX LOX and EPOX isozyme activities 1 JUMiner_v2.2 1 2 creutzfeldt 0 0 0 0 0 0 0 0 116142 16647138 151272 17610 9605 PTGS2 COX COX 18 2.9 ischemia AD PD ALS and CJD stimulation and upregulation of COX LOX and EPOX isozyme activities and the generation of excessive 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116143 16647138 151272 11934 6664 LOX LOX LOX 19 3.3 AD PD ALS and CJD stimulation and upregulation of COX LOX and EPOX isozyme activities and the generation of excessive amounts 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116144 16647138 151272 6701 3401 EPHX1 EPOX EPOX 21 2.9 ALS and CJD stimulation and upregulation of COX LOX and EPOX isozyme activities and the generation of excessive amounts of prostaglandins 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116145 16647138 151280 17610 9605 PTGS2 COX COX 8 2.9 These metabolites not only antagonize the effect of COX LOX and EPOX-generated products but also counteract leukocyte infiltration and 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116146 16647138 151280 11934 6664 LOX LOX LOX 9 3.3 These metabolites not only antagonize the effect of COX LOX and EPOX-generated products but also counteract leukocyte infiltration and proinflammatory 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116147 16647138 151280 6701 3401 EPHX1 EPOX EPOX-generated 11 1.6 metabolites not only antagonize the effect of COX LOX and EPOX-generated products but also counteract leukocyte infiltration and proinflammatory gene expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116148 16647138 151284 17610 9605 PTGS2 COX COX 5 2.9 Elevated activities of isoforms of COX LOX and EPOX at cellular and subcellular levels in ischemia 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 0 116149 16647138 151284 11934 6664 LOX LOX LOX 6 3.3 Elevated activities of isoforms of COX LOX and EPOX at cellular and subcellular levels in ischemia and 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 116150 16647138 151284 6701 3401 EPHX1 EPOX EPOX 8 2.9 Elevated activities of isoforms of COX LOX and EPOX at cellular and subcellular levels in ischemia and neurodegenerative diseases 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105593 16737688 136267 20996 11179 SOD1 SOD1 SOD1 9 4.2 expressing a mutated human Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 gene develop a motor neuron disease similar to familial amyotrophic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105594 16737688 136276 20996 11179 SOD1 ALS ALS 3 3.2 Amyotrophic lateral sclerosis (ALS) ALS is a rapidly progressive invariably fatal neurological disease of largely 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105595 16737688 136277 20996 11179 SOD1 ALS ALS 1 3.2 In ALS both the upper (UMN) UMN and the lower motor neurons 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105596 16737688 136277 11901 6637 LMNB1 LMN LMN 11 0.0 the upper (UMN) UMN and the lower motor neurons (LMN) LMN degenerate leading to progressive muscle weakness atrophy and finally complete 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105597 16737688 136278 20996 11179 SOD1 ALS ALS 0 3.2 ALS occurs in sporadic (SALS) SALS and familial forms (FALS) FALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105598 16737688 136279 20996 11179 SOD1 SOD1 SOD1 22 4.2 a mutant form of Cu/Zn Cu Zn superoxide dismutase (SOD1; SOD1 Rosen 1993 that normally functions in the regulation of oxidative 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105599 16737688 136280 20996 11179 SOD1 SOD1 SOD1 1 4.2 Mutant SOD1 produces motor neuron injury by a toxic gain of function 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105600 16737688 136282 20996 11179 SOD1 SOD1 SOD1 4 4.2 Now that _amp_#x3e 90 different SOD1 mutations have been described transgenic mouse models with these mutations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105601 16737688 136283 20996 11179 SOD1 SOD1 SOD1 6 4.2 Overexpression of the human Glycine 93_amp_#xa0 _amp_#x2192 _amp_#xa0 Alanine SOD1 mutation (SOD1-G93A) SOD1-G93A causes a phenotype that closely mimics the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105602 16737688 136283 20996 11179 SOD1 ALS ALS 19 3.2 causes a phenotype that closely mimics the neuropathological features of ALS ( Doble and Kennel 2000 Gurney et al. 1994 and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105603 16737688 136285 11901 6637 LMNB1 LMN LMNs 49 0.0 the neurodegenerative changes in SOD1-G93A transgenics are not confined to LMNs 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105604 16737688 136286 21920 11646 TCFL5 CHA Cha 45 0.0 while deleterious metabolic changes were shown in the hippocampus ( Cha et al. 2000 the red nucleus ( Chung et al. 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105605 16737688 136286 21920 11646 TCFL5 CHA Cha 62 0.0 red nucleus ( Chung et al. 2003b the cerebellum ( Cha et al. 2000 Chung et al. 2003b and Chung et 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105606 16737688 136288 20996 11179 SOD1 ALS ALS 12 3.2 latter issue would provide insights in the ongoing debate if ALS is due to anterograde (_amp_#x201c;dying-forward_amp_#x201d;) _amp_#x201c dying-forward_amp_#x201d or retrograde (_amp_#x201c;dying-back_amp_#x201d;) 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105607 16737688 136289 20996 11179 SOD1 ALS ALS 32 3.2 might be crucial for the progression of cell death in ALS ( Allan and Rothwell 2003 Czlonkowska et al. 2001 McGeer 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105608 16737688 136290 20996 11179 SOD1 ALS ALS 2 3.2 In fact ALS patients exhibit severe inflammatory reactions in the spinal cord ( 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105609 16737688 136292 20996 11179 SOD1 ALS ALS 38 3.2 and inflammatory changes in the CNS of the SOD1-G93A transgenic ALS model 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105610 16737688 136293 20996 11179 SOD1 ALS ALS 28 3.2 for the development of more effective even curative therapies for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105611 16737688 136299 20996 11179 SOD1 SOD1 SOD1 16 4.2 copies ( Gurney et al. 1994 of the human mutant SOD1 gene (Cu/Zn-SOD) Cu Zn-SOD containing the Gly 93 _amp_#xa0 _amp_#x2192 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105612 16737688 136300 20996 11179 SOD1 SOD1 SOD1 17 4.2 (PCR) PCR of tail DNA with primers specific for human SOD1 gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105613 16737688 136303 20996 11179 SOD1 SOD1 SOD1 0 4.2 SOD1 transgenics died between 5 and 6_amp_#xa0 months of age 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105614 16737688 136326 20996 11179 SOD1 SOD1 SOD1- 7 3.2 FluoroJade and silver staining as well as SOD1- and tyrosine hydroxylase-IHC (see see below were used to identify 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105615 16737688 136340 20996 11179 SOD1 SOD1 SOD1 9 4.2 Primary antibodies were used to further evaluate neurodegenerative alterations (SOD1 SOD1 and tyrosine hydroxylase to identify the molecular changes associated with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105616 16737688 136341 10734 6152 ITGAX CD11c CD11c 36 1.9 acidic protein T-cells (T-cell-receptor T-cell-receptor CD3 and dendritic cells (CD11c) CD11c 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105617 16737688 136345 10734 6152 ITGAX CD11c CD11c 8 1.9 Immunohistochemical stainings (IHC) IHC were performed either on cryostate (CD11c; CD11c Casp3act or on paraffin sections after deparaffinization and antigen retrieval 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105618 16737688 136345 20996 11179 SOD1 SOD1 SOD1 30 4.2 in 0.01_amp_#xa0 M citrate buffer pH 6.0 for CD3 PT66 SOD1 TH 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105619 16737688 136355 18175 9954 REL REL Rel 20 0.0 to a computer equipped with an image program (KS100 KS100 Rel 3.0 2 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 1 nf 105620 16737688 136357 20996 11179 SOD1 SOD1 SOD1- 8 3.2 Morphological signs of degeneration were semi-quantitatively evaluated in SOD1- or TH (for for catecholaminergic neurons -immunostained and in Gallyas-stained 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105621 16737688 136358 20996 11179 SOD1 SOD1 SOD1 0 4.2 SOD1 and TH immunoreactivities were observed throughout cellular somata and processes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105622 16737688 136359 8254 4235 GFAP GFAP GFAP- 8 2.5 For analysis of gliosis the staining intensity in GFAP- and PT66-immunostained sections and the number of CD3- CD11c- and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105623 16737688 136359 10734 6152 ITGAX CD11c CD11c- 17 1.9 in GFAP- and PT66-immunostained sections and the number of CD3- CD11c- and TB/Pin-positive TB Pin-positive cells were evaluated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105624 16737688 136362 20996 11179 SOD1 SOD1 SOD1- 4 3.2 The morphological changes in SOD1- or TH-stained sections the amount of Gallyas-positive structures and the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105625 16737688 136367 20996 11179 SOD1 SOD1 SOD1 6 4.2 Fig 2._amp_#xa0 Gallyas (A, A B D_amp_#x2013 K and SOD1 staining (C) C in transgenics at the age of 2_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105626 16737688 136373 20996 11179 SOD1 SOD1 SOD1 31 4.2 F H either silver-stained (A, A B or immunostained for SOD1 (C, C D GFAP (E, E F and PT66 (G, 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105627 16737688 136373 8254 4235 GFAP GFAP GFAP 34 2.5 (A, A B or immunostained for SOD1 (C, C D GFAP (E, E F and PT66 (G, G H 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105628 16737688 136374 20996 11179 SOD1 SOD1 SOD1 0 4.2 SOD1 immunostaining reveals vacuolar changes already in 3-month-old transgenics (arrows) arrows 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105629 16737688 136376 8254 4235 GFAP GFAP GFAP 2 2.5 Immunostainings for GFAP and PT66 show abundant reactive astrocytes and microglial cells at 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105630 16737688 136379 8254 4235 GFAP GFAP GFAP 33 2.5 (A_amp_#x2013;C) A_amp_#x2013 C or immunostained for TH (D_amp_#x2013;F), D_amp_#x2013 F GFAP (G_amp_#x2013;I) G_amp_#x2013 I and PT66 (J_amp_#x2013;L) J_amp_#x2013 L 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105631 16737688 136385 20996 11179 SOD1 SOD1 SOD1 28 4.2 F H either silver-stained (A, A B or immunostained for SOD1 (C, C D GFAP (E, E F and PT66 (G, 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105632 16737688 136385 8254 4235 GFAP GFAP GFAP 31 2.5 (A, A B or immunostained for SOD1 (C, C D GFAP (E, E F and PT66 (G, G H 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105633 16737688 136386 20996 11179 SOD1 SOD1 SOD1 12 4.2 arrows in panel C are visible at 4_amp_#xa0 months after SOD1 immunostaining (C), C while Gallyas staining is negative (A) A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105634 16737688 136388 8254 4235 GFAP GFAP GFAP 11 2.5 astrogliosis and microgliosis appear in this region as visualized by GFAP and PT66 immunostaining 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105635 16737688 136391 10734 6152 ITGAX CD11c CD11c-positive 7 1.9 Fig 6._amp_#xa0 Localization of CD3-positive T-cells (A) A and CD11c-positive dendritic cells (B_amp_#x2013;D) B_amp_#x2013 D in the locus coeruleus (A), 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105636 16737688 136398 20996 11179 SOD1 SOD1 SOD1 1 4.2 The SOD1 transgenics showed first signs of hindlimb paresis at 3.5_amp_#x2013 5_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105637 16737688 136399 20996 11179 SOD1 SOD1 SOD1 15 4.2 motor activity progressively decreased and at 3.5_amp_#xa0 months of age SOD1 transgenics were significantly ( P _amp_#xa0 _amp_#x2264 _amp_#xa0 0.05 less 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105638 16737688 136409 20996 11179 SOD1 SOD1 SOD1 3 4.2 Most of the SOD1 immunoreactivity was observed in the cytoplasm although less intense staining 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105639 16737688 136411 20996 11179 SOD1 SOD1 SOD1- 1 3.2 Both SOD1- and TH-ip cells appeared morphologically unaltered in non-transgenic animals 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105640 16737688 136415 20996 11179 SOD1 SOD1 SOD1 15 4.2 describe chronologically the degenerative changes and inflammatory reactions in the SOD1 transgenics while the figures and tables illustrate the pathological changes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105641 16737688 136418 20996 11179 SOD1 SOD1 SOD1 2 4.2 In the SOD1 transgenics the first morphological signs of degeneration were notable by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105642 16737688 136423 20996 11179 SOD1 SOD1 SOD1- 5 3.2 At the age of 3_amp_#xa0 months SOD1- and TH-IHC revealed pathological alterations of the neuropil in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105643 16737688 136427 20996 11179 SOD1 SOD1 SOD1- 2 3.2 In addition SOD1-/TH-IHC SOD1- TH-IHC pointed out lesions in the neuropil of the ventral 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105644 16737688 136437 8254 4235 GFAP GFAP GFAP 4 2.5 Immunostainings with the antibodies GFAP and PT66 revealed an increase in glial cell number and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105645 16737688 136440 8254 4235 GFAP GFAP GFAP 6 2.5 Surprisingly no differences in PT66 and GFAP staining patterns between transgenics and littermates were found in the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105646 16737688 136445 10734 6152 ITGAX CD11c CD11c-positive 1 1.9 Likewise CD11c-positive cells emerged first in the spinal cord ( Fig 6 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 105647 16737688 136450 20996 11179 SOD1 ALS ALS 24 3.2 reactions in the brain of a transgenic animal model of ALS the SOD1-G93A mouse 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105648 16737688 136470 20996 11179 SOD1 ALS ALS 50 3.2 Gurney 1994 and strikingly similar to those seen in human ALS ( Okamoto et al. 1990 and Takahashi et al. 1997 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105649 16737688 136479 20996 11179 SOD1 ALS ALS 14 3.2 animal model substantial degenerative changes in the cerebral cortex of ALS patients are well known ( Kiernan and Hudson 1991 Lloyd 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105650 16737688 136480 20996 11179 SOD1 SOD1 SOD1 9 4.2 Despite the close similarities between the histopathology of transgenic SOD1 mice and ALS the experimental model departs from the human 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105651 16737688 136480 20996 11179 SOD1 ALS ALS 12 3.2 close similarities between the histopathology of transgenic SOD1 mice and ALS the experimental model departs from the human disease in an 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105652 16737688 136484 20996 11179 SOD1 ALS ALS 27 3.2 (_amp_#x201c;dying-back_amp_#x201d;) _amp_#x201c dying-back_amp_#x201d degeneration ( Eisen and Weber 2001 in ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105653 16737688 136491 20996 11179 SOD1 ALS ALS-affected 20 3.2 and astrocyte activation in the brain as described for the ALS-affected spinal cord ( Alexianu et al. 2001 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105654 16737688 136495 10734 6152 ITGAX CD11c CD11c 13 1.9 our study was the infiltration of single T-lymphocytes and CD11c(+) CD11c cells in brain regions that were most heavily degenerated like 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 105655 16737688 136496 10734 6152 ITGAX CD11c CD11c 5 1.9 The integrin alpha X subunit (CD11c) CD11c is a known marker for dendritic cells (DC) DC ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105656 16737688 136497 10734 6152 ITGAX CD11c CD11c 4 1.9 However recent publications reported CD11c expression on a subset of cytotoxic T-cells in the intestine 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105657 16737688 136498 10734 6152 ITGAX CD11c CD11c 2 1.9 Since the CD11c(+) CD11c cells that appeared in late-stage SOD1-G93A transgenics (i) i were 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 105658 16737688 136501 20996 11179 SOD1 ALS ALS 6 3.2 (2004) 2004 in the spinal cord of ALS patients and that of Henkel et al 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105659 16737688 136506 20996 11179 SOD1 ALS ALS 38 3.2 and Reichmann 2001 and Serafini et al. 2000 in the ALS transgenics we found some dendritic cells and single T-lymphocytes after 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105660 16737688 136509 20996 11179 SOD1 ALS ALS 15 3.2 specify the role of inflammatory reactions in the neurodegeneration in ALS the strong immune activation in the brain suggests that inflammatory 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105661 16737688 136509 20996 11179 SOD1 ALS ALS 40 3.2 an important role in spinal cord but also in brain ALS pathology 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00069434132908573<>ScoreDetail__5468|IGFALS|0.000360161352285824__11179|SOD1|0.00069434132908573__ 0 0 0 0 0 105850 16753239 137022 17031 9232 PPARA PPAR PPARs 3 1.9 Peroxisome proliferator-activated receptors (PPARs) PPARs play key roles in lipid metabolism and inflammation 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105851 16753239 137023 17031 9232 PPARA PPAR PPARs 4 1.9 Recent studies indicated that PPARs are also capable of modulating immune responses 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105852 16753239 137026 20996 11179 SOD1 ALS ALS 34 0.9 (AD), AD Parkinson's disease (PD), PD amyotrophic lateral sclerosis (ALS), ALS and stroke 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000580796516805404<>ScoreDetail__5468|IGFALS|0.000384737206593143__11179|SOD1|0.000580796516805404__ 0 0 0 0 0 105853 16753239 137027 17031 9232 PPARA PPAR PPAR 6 1.9 A review of the role of PPAR agonists in modulating glial cell activation is presented 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105854 16753239 137028 17031 9232 PPARA PPAR PPAR 12 1.9 a discussion of the molecular mechanisms of action of these PPAR agonists and the potential utility of these agents for the 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105855 16753239 137031 17031 9232 PPARA PPAR PPARs 3 1.9 Peroxisome proliferator-activated receptors (PPARs) PPARs are members of a superfamily of proteins termed nuclear receptors 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105856 16753239 137033 17031 9232 PPARA PPAR PPARs 3 1.9 The role of PPARs in regulating the transcription of genes involved in glucose and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105857 16753239 137035 17031 9232 PPARA PPAR PPAR 4 1.9 Three major subtypes of PPAR exist which are designated PPAR-_amp_#x3b1 -_amp_#x3b2;/_amp_#x3b4;, -_amp_#x3b2 _amp_#x3b4 and -_amp_#x3b3 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105858 16753239 137035 17031 9232 PPARA PPAR PPAR-A 9 1.9 Three major subtypes of PPAR exist which are designated PPAR-_amp_#x3b1 -_amp_#x3b2;/_amp_#x3b4;, -_amp_#x3b2 _amp_#x3b4 and -_amp_#x3b3 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105859 16753239 137037 17034 9236 PPARG PPAR PPAR-G 14 1.9 commonly prescribed for the treatment of type II diabetes are PPAR-_amp_#x3b3 ligands 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105860 16753239 137038 17034 9236 PPARG PPAR PPAR-G 2 1.9 Naturally occurring PPAR-_amp_#x3b3 ligands include eicosanoids polyunsaturated fatty acids and the cyclopentenone prostaglandin 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105861 16753239 137039 17034 9236 PPARG PPAR PPAR-G 14 1.9 NSAID including indomethacin which are used to treat inflammation are PPAR-_amp_#x3b3 ligands 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105862 16753239 137041 17031 9232 PPARA PPAR PPAR 8 1.9 These observations stimulated studies investigating the role of PPAR in modulating inflammation 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105863 16753239 137042 17034 9236 PPARG PPAR PPAR-G 8 1.9 Critical early studies in this field demonstrated that PPAR-_amp_#x3b3 agonists are capable of suppressing immune activation of monocyte/macrophages monocyte 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105864 16753239 137043 17031 9232 PPARA PPAR PPAR-A 0 1.9 PPAR-_amp_#x3b1 ligands include fibrates that are commonly used for the treatment 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105865 16753239 137045 17031 9232 PPARA PPAR PPAR-A 15 1.9 acid eicosapentanoic acid and linoleic acid are endogenous ligands for PPAR-_amp_#x3b1 while WY 14 643 and GW7647 are synthetic agonists of 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105866 16753239 137046 17033 9235 PPARD PPAR PPAR-B 0 1.9 PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 agonists include various fatty acids including bromopalmitate the prostacyclin 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105867 16753239 137047 17031 9232 PPARA PPAR PPARs 0 1.9 PPARs are capable of regulating gene expression through multiple mechanisms 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105868 16753239 137048 17031 9232 PPARA PPAR PPARs 0 1.9 PPARs generally function as heterodimers in association with retinoid-X-receptors (RXRs) RXRs 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105869 16753239 137051 17031 9232 PPARA PPAR PPARs 8 1.9 In addition through a mechanism termed receptor-dependent transrepression PPARs are also capable of regulating gene expression independent of binding 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105870 16753239 137053 17031 9232 PPARA PPAR PPAR 2 1.9 In addition PPAR interaction with transcriptional co-activator/co-repressor co-activator co-repressor molecules that are in 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105871 16753239 137055 17034 9236 PPARG PPAR PPAR-G 0 1.9 PPAR-_amp_#x3b3 agonists are believed to suppress immune responses principally through transrepression 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105872 16753239 137056 7683 3796 FOS AP-1 AP-1 9 1.0 For example these agonists inhibit transcription factors including NF-_amp_#x3ba B AP-1 and STAT-1 from activating gene expression in this manner 1 JUMiner_v2.2 1 0 0 2 6204 TotalCon:5<>3796|FOS|2353|Complete__3797|FOSB|2354|Complete__6204|JUN|3725|Complete__6205|JUNB|3726|Complete__6206|JUND|3727|Complete__<>AvaiableGeneRif=5<>BEST:6204|JUN|0.000801660044919879<>ScoreDetail__3796|FOS|0.000707726384015202__3797|FOSB|0.000561083548373237__6205|JUNB|0.000698883615753056__6204|JUN|0.000801660044919879__6206|JUND|0.000662022335145468__ 0 0 0 0 0 105873 16753239 137056 21414 11362 STAT1 STAT1 STAT-1 11 0.5 these agonists inhibit transcription factors including NF-_amp_#x3ba B AP-1 and STAT-1 from activating gene expression in this manner 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105874 16753239 137057 17034 9236 PPARG PPAR PPAR-G 1 1.9 The PPAR-_amp_#x3b3 agonist 15d-PGJ 2 can regulate gene expression through receptor-independent mechanisms 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105875 16753239 137059 17031 9232 PPARA PPAR PPAR-A 0 1.9 PPAR-_amp_#x3b1 agonists also inhibit NF-_amp_#x3ba B activity by inducing the expression 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105876 16753239 137072 17031 9232 PPARA PPAR PPARs 2 1.9 Effects of PPARs on glial cell activation 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105877 16753239 137074 17034 9236 PPARG PPAR PPAR-G 0 1.9 PPAR-_amp_#x3b3 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105878 16753239 137075 17034 9236 PPARG PPAR PPAR-G 1 1.9 The PPAR-_amp_#x3b3 agonist 15d-PGJ 2 was demonstrated to inhibit NO IL-1_amp_#x3b2 and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105879 16753239 137075 22551 11892 TNF TNF TNF-A 12 0.0 agonist 15d-PGJ 2 was demonstrated to inhibit NO IL-1_amp_#x3b2 and TNF-_amp_#x3b1 production by the BV-2 mouse microglial cell line ( Koppal 11 JUMiner_v2.2 1 1 tnf; 0 0 0 0 0 0 0 0 105880 16753239 137076 17034 9236 PPARG PPAR PPAR-G 1 1.9 The PPAR-_amp_#x3b3 agonist troglitazone did not suppress the expression of these pro-inflammatory 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105881 16753239 137076 17034 9236 PPARG PPAR PPAR-G 23 1.9 by BV-2 cells suggesting that 15d-PGJ 2 may act through PPAR-_amp_#x3b3 -independent mechanisms ( Petrova et al. 1999 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105882 16753239 137078 9353 4931 HLA-A MHC MHC 14 0.3 al. 2000 demonstrated that 15d-PGJ 2 suppressed TNF-_amp_#x3b1 NO and MHC class II expression by primary rat microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105883 16753239 137078 22551 11892 TNF TNF TNF-A 11 0.0 ( Bernardo et al. 2000 demonstrated that 15d-PGJ 2 suppressed TNF-_amp_#x3b1 NO and MHC class II expression by primary rat microglia 11 JUMiner_v2.2 1 1 tnf; 0 0 0 0 0 0 0 0 105884 16753239 137079 17034 9236 PPARG PPAR PPAR-G 3 1.9 However since the PPAR-_amp_#x3b3 agonist ciglitazone suppressed the production of these pro-inflammatory molecules in 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105885 16753239 137079 17034 9236 PPARG PPAR PPAR-G 25 1.9 similar manner 15d-PGJ 2 was interpreted to act through a PPAR-_amp_#x3b3 dependent mechanism 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105886 16753239 137082 17034 9236 PPARG PPAR PPAR-G 6 1.9 In these studies HCT1026 activated the PPAR-_amp_#x3b3 receptor in microglia and the PPAR-_amp_#x3b3 antagonist GW9662 blocked receptor 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105887 16753239 137082 17034 9236 PPARG PPAR PPAR-G 12 1.9 studies HCT1026 activated the PPAR-_amp_#x3b3 receptor in microglia and the PPAR-_amp_#x3b3 antagonist GW9662 blocked receptor activation ( Bernardo et al. 2005 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105888 16753239 137083 17034 9236 PPARG PPAR PPAR-G 10 1.9 The basis for the discrepancy between these studies concerning whether PPAR-_amp_#x3b3 agonists influence microglial cell function through PPAR-_amp_#x3b3 -dependent or -independent 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105889 16753239 137083 17034 9236 PPARG PPAR PPAR-G 17 1.9 studies concerning whether PPAR-_amp_#x3b3 agonists influence microglial cell function through PPAR-_amp_#x3b3 -dependent or -independent mechanisms may be explained by the fact 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105890 16753239 137084 17034 9236 PPARG PPAR PPAR-G 17 1.9 conducted with BV-2 microglial cells which express little or no PPAR-_amp_#x3b3 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105891 16753239 137085 10463 6018 IL6 IL-6 IL-6 28 1.0 15d-PGJ 2 inhibited NO as well as the cytokines IL-1_amp_#x3b2 IL-6 and TNF-_amp_#x3b1 and the chemokine MCP-1 by both primary mouse 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105892 16753239 137085 3758 10618 CCL2 MCP-1 MCP-1 34 1.3 as the cytokines IL-1_amp_#x3b2 IL-6 and TNF-_amp_#x3b1 and the chemokine MCP-1 by both primary mouse microglia and astrocytes ( Storer et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105893 16753239 137085 22551 11892 TNF TNF TNF-A 30 0.1 inhibited NO as well as the cytokines IL-1_amp_#x3b2 IL-6 and TNF-_amp_#x3b1 and the chemokine MCP-1 by both primary mouse microglia and 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105894 16753239 137086 17034 9236 PPARG PPAR PPAR-G 24 1.9 molecules in spite of the fact that this agonist binds PPAR-_amp_#x3b3 with lower affinity than thiazolidinediones 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105895 16753239 137088 17034 9236 PPARG PPAR PPAR-G 17 1.9 RA may inhibit cell activation through the formation of PPAR-_amp_#x3b3;/RXR PPAR-_amp_#x3b3 RXR heterodimers 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105896 16753239 137089 17034 9236 PPARG PPAR PPAR-G 3 1.9 The expression of PPAR-_amp_#x3b3 increases in microglia and astrocytes during EAE supporting a role 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105897 16753239 137090 16440 8884 PGA PGA PGA 1 0.3 Interestingly PGA 2 which like 15d-PGJ 2 is a cyclopentenone prostaglandin but 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 105898 16753239 137090 17034 9236 PPARG PPAR PPAR-G 18 1.9 is a cyclopentenone prostaglandin but is not believed to bind PPAR-_amp_#x3b3 is a potent inhibitor of the activation of primary mouse 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105899 16753239 137091 17034 9236 PPARG PPAR PPAR-G 13 1.9 suggest that 15d-PGJ 2 likely inhibits glial cell activation by PPAR-_amp_#x3b3 -dependent as well as PPAR-_amp_#x3b3 -independent mechanisms 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105900 16753239 137091 17034 9236 PPARG PPAR PPAR-G 17 1.9 inhibits glial cell activation by PPAR-_amp_#x3b3 -dependent as well as PPAR-_amp_#x3b3 -independent mechanisms 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105901 16753239 137092 17034 9236 PPARG PPAR PPAR-G 0 1.9 PPAR-_amp_#x3b3 agonists are capable of inhibiting inflammatory responses in glia through 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105902 16753239 137094 17034 9236 PPARG PPAR PPAR-G 4 1.9 (2004) 2004 demonstrated that the PPAR-_amp_#x3b3 agonist 15d-PGJ 2 inhibited LPS induction of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105903 16753239 137094 10463 6018 IL6 IL-6 IL-6 16 1.0 15d-PGJ 2 inhibited LPS induction of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IL-6 in primary astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105904 16753239 137094 24053 12728 VWS LPS LPS 9 0.0 (2004) 2004 demonstrated that the PPAR-_amp_#x3b3 agonist 15d-PGJ 2 inhibited LPS induction of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IL-6 in primary astrocytes 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 105905 16753239 137094 22551 11892 TNF TNF TNF-A 13 0.0 the PPAR-_amp_#x3b3 agonist 15d-PGJ 2 inhibited LPS induction of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IL-6 in primary astrocytes 11 JUMiner_v2.2 1 1 tnf; 0 0 0 0 0 0 0 0 105906 16753239 137095 17034 9236 PPARG PPAR PPAR-G 8 1.9 Over expression of wild-type and dominant-negative constructs of PPAR-_amp_#x3b3 or the PPAR-_amp_#x3b3 antagonist GW9662 did not alter NO and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105907 16753239 137095 17034 9236 PPARG PPAR PPAR-G 11 1.9 expression of wild-type and dominant-negative constructs of PPAR-_amp_#x3b3 or the PPAR-_amp_#x3b3 antagonist GW9662 did not alter NO and iNOS expression in 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105908 16753239 137095 14535 7873 NOS2A iNOS iNOS 19 1.5 or the PPAR-_amp_#x3b3 antagonist GW9662 did not alter NO and iNOS expression in these cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105909 16753239 137099 17034 9236 PPARG PPAR PPAR-G 4 1.9 (2003) 2003 demonstrated that the PPAR-_amp_#x3b3 agonists 15d-PGJ 2 and rosiglitazone inhibit the phosphorylation of STAT1 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105910 16753239 137099 21414 11362 STAT1 STAT1 STAT1 14 0.5 PPAR-_amp_#x3b3 agonists 15d-PGJ 2 and rosiglitazone inhibit the phosphorylation of STAT1 STAT3 JAK1 and JAK2 in microglia and astrocytes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105911 16753239 137099 10781 6190 JAK1 JAK1 JAK1 16 0.3 15d-PGJ 2 and rosiglitazone inhibit the phosphorylation of STAT1 STAT3 JAK1 and JAK2 in microglia and astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105912 16753239 137099 10782 6192 JAK2 JAK2 JAK2 16 0.3 15d-PGJ 2 and rosiglitazone inhibit the phosphorylation of STAT1 STAT3 JAK1 and JAK2 in microglia and astrocytes 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105913 16753239 137099 10782 6192 JAK2 JAK2 JAK2 18 0.3 and rosiglitazone inhibit the phosphorylation of STAT1 STAT3 JAK1 and JAK2 in microglia and astrocytes 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105914 16753239 137099 21416 11364 STAT3 STAT3 STAT3 15 0.4 agonists 15d-PGJ 2 and rosiglitazone inhibit the phosphorylation of STAT1 STAT3 JAK1 and JAK2 in microglia and astrocytes 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105915 16753239 137100 4413 1984 CISH SOCS SOCS 15 1.6 agonists induce the expression of suppressor of cytokine signaling (SOCS) SOCS 1 and 3 which alters JAK/STAT JAK STAT phosphorylation and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105916 16753239 137100 21414 11362 STAT1 STAT STAT 21 0.5 signaling (SOCS) SOCS 1 and 3 which alters JAK/STAT JAK STAT phosphorylation and JAK/STAT JAK STAT mediated signaling 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105917 16753239 137100 21414 11362 STAT1 STAT STAT 24 0.5 3 which alters JAK/STAT JAK STAT phosphorylation and JAK/STAT JAK STAT mediated signaling 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105918 16753239 137101 17034 9236 PPARG PPAR PPAR-G 0 1.9 PPAR-_amp_#x3b3 agonist suppression of glial activation can have profound effects on 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105919 16753239 137103 926 620 APP amyloid amyloid 6 1.0 (2000) 2000 demonstrated that conditioned media from _amp_#x3b2 -amyloid treated primary mouse microglia was toxic to mouse cortical neurons 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 105920 16753239 137104 926 620 APP amyloid amyloid 6 1.0 However troglitazone treatment of microglia suppressed _amp_#x3b2 -amyloid mediated neuron cell death 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 105921 16753239 137105 17034 9236 PPARG PPAR PPAR-G 8 1.9 These studies further demonstrated that a variety of PPAR-_amp_#x3b3 agonists including TZDs 15d-PGJ 2 and NSAIDS blocked _amp_#x3b2 -amyloid 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105922 16753239 137105 926 620 APP amyloid amyloid 18 1.0 PPAR-_amp_#x3b3 agonists including TZDs 15d-PGJ 2 and NSAIDS blocked _amp_#x3b2 -amyloid induction of neurotoxic molecules by monocytes 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 105923 16753239 137106 17034 9236 PPARG PPAR PPAR-G 3 1.9 For example these PPAR-_amp_#x3b3 agonists blocked TNF-_amp_#x3b1 and IL-6 expression by monocytes 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105924 16753239 137106 10463 6018 IL6 IL-6 IL-6 8 1.0 For example these PPAR-_amp_#x3b3 agonists blocked TNF-_amp_#x3b1 and IL-6 expression by monocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105925 16753239 137106 22551 11892 TNF TNF TNF-A 6 0.1 For example these PPAR-_amp_#x3b3 agonists blocked TNF-_amp_#x3b1 and IL-6 expression by monocytes 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105926 16753239 137107 17034 9236 PPARG PPAR PPAR-G 5 1.9 Collectively this study demonstrated that PPAR-_amp_#x3b3 agonists suppress the production by monocyte/microglial monocyte microglial cells of 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105927 16753239 137108 17034 9236 PPARG PPAR PPAR-G 14 1.9 by studies utilizing rat cortical neuron-glial co-cultures that indicated that PPAR-_amp_#x3b3 agonists including TZDs and 15d-PGJ 2 suppressed LPS induction of 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105928 16753239 137108 24053 12728 VWS LPS LPS 22 0.0 indicated that PPAR-_amp_#x3b3 agonists including TZDs and 15d-PGJ 2 suppressed LPS induction of neuronal cell death ( Kim et al. 2002 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 105929 16753239 137109 17031 9232 PPARA PPAR PPAR-A 2 1.9 Interestingly the PPAR-_amp_#x3b1 agonists clofibrate and WY14 643 did not protect neurons in 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105930 16753239 137110 14535 7873 NOS2A iNOS iNOS 9 1.5 Recent studies demonstrated that TZDs block the production of iNOS TNF-_amp_#x3b1 IL-6 and COX-2 by primary rat microglia and astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105931 16753239 137110 10463 6018 IL6 IL-6 IL-6 11 1.0 studies demonstrated that TZDs block the production of iNOS TNF-_amp_#x3b1 IL-6 and COX-2 by primary rat microglia and astrocytes and protected 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105932 16753239 137110 17610 9605 PTGS2 COX-2 COX-2 13 1.0 that TZDs block the production of iNOS TNF-_amp_#x3b1 IL-6 and COX-2 by primary rat microglia and astrocytes and protected cortical neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105933 16753239 137110 22551 11892 TNF TNF TNF-A 10 0.4 Recent studies demonstrated that TZDs block the production of iNOS TNF-_amp_#x3b1 IL-6 and COX-2 by primary rat microglia and astrocytes and 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105934 16753239 137111 17034 9236 PPARG PPAR PPAR-G 1 1.9 A PPAR-_amp_#x3b3 antagonist blocked TZD protection of cortical neurons in these studies 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105935 16753239 137112 17031 9232 PPARA PPAR PPARs 1 1.9 Interestingly PPARs including PPAR-_amp_#x3b3 can be expressed by neurons ( Cimini et 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105936 16753239 137112 17034 9236 PPARG PPAR PPAR-G 3 1.9 Interestingly PPARs including PPAR-_amp_#x3b3 can be expressed by neurons ( Cimini et al. 2005 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105937 16753239 137113 17031 9232 PPARA PPAR PPAR 6 1.9 Furthermore it has been suggested that PPAR activation in neurons may directly influence neuron cell viability and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105938 16753239 137114 17034 9236 PPARG PPAR PPAR-G 12 1.9 are required to more definitively determine the mechanisms by which PPAR-_amp_#x3b3 agonists modulate inflammatory responses in the CNS 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105939 16753239 137115 17034 9236 PPARG PPAR PPAR-G 17 1.9 or receptor-independent mechanisms are complicated by the paucity of specific PPAR-_amp_#x3b3 agonists and the fact that PPAR-_amp_#x3b3 -deficient mice die soon 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105940 16753239 137115 17034 9236 PPARG PPAR PPAR-G 23 1.9 the paucity of specific PPAR-_amp_#x3b3 agonists and the fact that PPAR-_amp_#x3b3 -deficient mice die soon after birth 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105941 16753239 137116 17034 9236 PPARG PPAR PPAR-G 2 1.9 In addition PPAR-_amp_#x3b3 agonists have been demonstrated in some studies to function through 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105942 16753239 137116 17031 9232 PPARA PPAR PPARs 28 1.9 but receptor-independent mechanisms at higher concentrations perhaps by activating other PPARs ( Welch et al. 2003 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105943 16753239 137117 17034 9236 PPARG PPAR PPAR-G 5 1.9 The development of highly selective PPAR-_amp_#x3b3 antagonists and conditional PPAR-_amp_#x3b3 deficient mouse strains will be essential 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105944 16753239 137117 17034 9236 PPARG PPAR PPAR-G 9 1.9 The development of highly selective PPAR-_amp_#x3b3 antagonists and conditional PPAR-_amp_#x3b3 deficient mouse strains will be essential in determining the mechanisms 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105945 16753239 137117 17034 9236 PPARG PPAR PPAR-G 22 1.9 strains will be essential in determining the mechanisms by which PPAR-_amp_#x3b3 agonists control CNS inflammation 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105946 16753239 137119 17031 9232 PPARA PPAR PPAR-A 0 1.9 PPAR-_amp_#x3b1 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105947 16753239 137120 17031 9232 PPARA PPAR PPAR-A 8 1.9 Relatively few studies have investigated the effects of PPAR-_amp_#x3b1 agonists on glial cell activation 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105948 16753239 137122 17031 9232 PPARA PPAR PPAR-A 4 1.9 (2002) 2002 demonstrated that the PPAR-_amp_#x3b1 agonist gemfibrozil inhibited cytokine induction of NO and iNOS by 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105949 16753239 137122 14535 7873 NOS2A iNOS iNOS 13 1.5 the PPAR-_amp_#x3b1 agonist gemfibrozil inhibited cytokine induction of NO and iNOS by human astroglial and primary astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105950 16753239 137123 17031 9232 PPARA PPAR PPAR-A 7 1.9 Gemfibrozil was suggested to function in a PPAR-_amp_#x3b1 independent manner in these studies since a dominant negative PPAR-_amp_#x3b1 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105951 16753239 137123 17031 9232 PPARA PPAR PPAR-A 17 1.9 PPAR-_amp_#x3b1 independent manner in these studies since a dominant negative PPAR-_amp_#x3b1 mutant did not overcome gemfibrozil mediated inhibition of iNOS gene 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105952 16753239 137123 14535 7873 NOS2A iNOS iNOS 26 1.5 negative PPAR-_amp_#x3b1 mutant did not overcome gemfibrozil mediated inhibition of iNOS gene expression following transient transfection of astroglial cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105953 16753239 137124 7683 3796 FOS AP-1 AP-1 11 1.0 studies indicated that gemfibrozil suppressed cytokine induction of NF-_amp_#x3ba B AP-1 and C/EBP-_amp_#x3b2;-dependent C EBP-_amp_#x3b2 -dependent luciferase activity following transfection into 1 JUMiner_v2.2 1 0 0 2 6204 TotalCon:5<>3796|FOS|2353|Complete__3797|FOSB|2354|Complete__6204|JUN|3725|Complete__6205|JUNB|3726|Complete__6206|JUND|3727|Complete__<>AvaiableGeneRif=5<>BEST:6204|JUN|0.000801660044919879<>ScoreDetail__3796|FOS|0.000707726384015202__3797|FOSB|0.000561083548373237__6205|JUNB|0.000698883615753056__6204|JUN|0.000801660044919879__6206|JUND|0.000662022335145468__ 0 0 0 0 0 105954 16753239 137124 6328 3133 EBP EBP EBP-_amp_#x3b2 13 0.3 suppressed cytokine induction of NF-_amp_#x3ba B AP-1 and C/EBP-_amp_#x3b2;-dependent C EBP-_amp_#x3b2 -dependent luciferase activity following transfection into glial cells 11 JUMiner_v2.2 1 0 0 2 4298 TotalCon:3<>3133|EBP|10682|Complete__4298|GLB1|2720|Complete__30418|SH3D19|152503|Complete__<>AvaiableGeneRif=3<>BEST:4298|GLB1|0.000492277518999755<>ScoreDetail__3133|EBP|0.000324668870881178__4298|GLB1|0.000492277518999755__30418|SH3D19|0.000265587970907902__ 0 0 0 0 0 105955 16753239 137125 17031 9232 PPARA PPAR PPAR-A 7 1.9 We recently demonstrated that a variety of PPAR-_amp_#x3b1 agonists inhibit the production of NO as well as the 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105956 16753239 137125 10463 6018 IL6 IL-6 IL-6 22 1.0 of NO as well as the pro-inflammatory cytokines TNF-_amp_#x3b1 IL-1_amp_#x3b2 IL-6 IL-12 p40 and the chemokine MCP-1 by primary mouse microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105957 16753239 137125 6327 15531 EBNA1BP2 p40 p40 24 0.3 as well as the pro-inflammatory cytokines TNF-_amp_#x3b1 IL-1_amp_#x3b2 IL-6 IL-12 p40 and the chemokine MCP-1 by primary mouse microglia 1 JUMiner_v2.2 1 0 0 2 682 TotalCon:9<>682|ARHGEF2|9181|Complete__15531|EBNA1BP2|10969|Complete__9565|PSMD7|5713|Complete__6029|IL9|3578|Complete__6508|LANCL1|10314|No_GeneRif__6502|RPSA|3921|Complete__6871|MAPK1|5594|Complete__16896|RABEPK|10244|Complete__15979|TP63|8626|Complete__<>AvaiableGeneRif=8<>BEST:682|ARHGEF2|0.0010304951778643<>ScoreDetail__15979|TP63|0.000629059589589131__16896|RABEPK|0.000576121598430988__6502|RPSA|0.000530315737861447__15531|EBNA1BP2|0.000653755005311759__682|ARHGEF2|0.0010304951778643__9565|PSMD7|0.00016343875132794__6029|IL9|0.00071221120104219__6871|MAPK1|0.000977108762759342__ 0 0 0 0 0 105958 16753239 137125 3758 10618 CCL2 MCP-1 MCP-1 28 1.3 pro-inflammatory cytokines TNF-_amp_#x3b1 IL-1_amp_#x3b2 IL-6 IL-12 p40 and the chemokine MCP-1 by primary mouse microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105959 16753239 137125 22551 11892 TNF TNF TNF-A 20 0.1 the production of NO as well as the pro-inflammatory cytokines TNF-_amp_#x3b1 IL-1_amp_#x3b2 IL-6 IL-12 p40 and the chemokine MCP-1 by primary 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105960 16753239 137126 17031 9232 PPARA PPAR PPAR-A 2 1.9 Interestingly the PPAR-_amp_#x3b1 agonist fenofibrate in combination with the retinoid X receptor agonist 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105961 16753239 137126 10463 6018 IL6 IL-6 IL-6 25 1.0 retinoic acid suppressed microglial production of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IL-6 in an additive manner ( Xu et al. 2005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105962 16753239 137126 22551 11892 TNF TNF TNF-A 22 0.0 receptor agonist 9-cis retinoic acid suppressed microglial production of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 and IL-6 in an additive manner ( Xu et 11 JUMiner_v2.2 1 1 tnf; 0 0 0 0 0 0 0 0 105963 16753239 137127 10463 6018 IL6 IL-6 IL-6 19 1.0 additive manner in inhibiting LPS induction of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 IL-6 and MCP-1 expression in primary astrocytes (unpublished unpublished data 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105964 16753239 137127 3758 10618 CCL2 MCP-1 MCP-1 21 1.3 in inhibiting LPS induction of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 IL-6 and MCP-1 expression in primary astrocytes (unpublished unpublished data 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105965 16753239 137127 24053 12728 VWS LPS LPS 13 0.0 and 9-cis RA acted in an additive manner in inhibiting LPS induction of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 IL-6 and MCP-1 expression in 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 105966 16753239 137127 22551 11892 TNF TNF TNF-A 17 0.1 in an additive manner in inhibiting LPS induction of NO TNF-_amp_#x3b1 IL-1_amp_#x3b2 IL-6 and MCP-1 expression in primary astrocytes (unpublished unpublished 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105967 16753239 137128 17031 9232 PPARA PPAR PPAR-A 5 1.9 Finally our studies suggest that PPAR-_amp_#x3b1 agonists inhibit glial activation at least in part by suppressing 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105968 16753239 137129 17031 9232 PPARA PPAR PPAR-A 5 1.9 In summary we demonstrate that PPAR-_amp_#x3b1 agonists attenuate microglia and astrocyte activation in vitro 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105969 16753239 137130 17031 9232 PPARA PPAR PPAR-A 6 1.9 These results raise the possibility that PPAR-_amp_#x3b1 agonists might have benefit as a therapy in a variety 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105970 16753239 137132 17033 9235 PPARD PPAR PPAR-B 0 1.9 PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105971 16753239 137133 17033 9235 PPARD PPAR PPAR-B 3 1.9 The effects of PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 agonists on glial cell activation have not been examined 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105972 16753239 137134 17033 9235 PPARD PPAR PPAR-B 6 1.9 However a recent study demonstrated the PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 agonist GW0742 modestly inhibited LPS induction of NO production 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105973 16753239 137134 24053 12728 VWS LPS LPS 11 0.0 study demonstrated the PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 agonist GW0742 modestly inhibited LPS induction of NO production in both primary rat microglia and 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 105974 16753239 137135 17034 9236 PPARG PPAR PPAR-G 4 1.9 This suggests that like PPAR-_amp_#x3b3 and PPAR-_amp_#x3b1 agonists PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 agonists may suppress chronic 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105975 16753239 137135 17031 9232 PPARA PPAR PPAR-A 6 1.9 This suggests that like PPAR-_amp_#x3b3 and PPAR-_amp_#x3b1 agonists PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 agonists may suppress chronic glial activation 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105976 16753239 137135 17033 9235 PPARD PPAR PPAR-B 8 1.9 This suggests that like PPAR-_amp_#x3b3 and PPAR-_amp_#x3b1 agonists PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 agonists may suppress chronic glial activation which could protect 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105977 16753239 137137 17031 9232 PPARA PPAR PPARs 2 1.9 Effects of PPARs on neuroinflammatory and neurodegenerative disorders 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105978 16753239 137140 17034 9236 PPARG PPAR PPAR-G 0 1.9 PPAR-_amp_#x3b3 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105979 16753239 137143 17034 9236 PPARG PPAR PPAR-G 5 1.9 (2001) 2001 first demonstrated that the PPAR-_amp_#x3b3 agonist troglitazone inhibited the development of EAE 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105980 16753239 137145 17034 9236 PPARG PPAR PPAR-G 4 1.9 (2002) 2002 showed that the PPAR-_amp_#x3b3 agonist 15d-PGJ 2 inhibited T cell proliferation 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105981 16753239 137146 10480 5962 IL10 IL-10 IL-10 5 1.0 Additionally this agonist suppressed IFN-_amp_#x3b3 IL-10 and IL-4 production by activated lymphocytes ( Diab et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105982 16753239 137146 10458 6014 IL4 IL-4 IL-4 7 1.0 Additionally this agonist suppressed IFN-_amp_#x3b3 IL-10 and IL-4 production by activated lymphocytes ( Diab et al. 2002 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105983 16753239 137146 9905 5438 IFNG IFN IFN-G 4 0.2 Additionally this agonist suppressed IFN-_amp_#x3b3 IL-10 and IL-4 production by activated lymphocytes ( Diab et 5 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000745162298178483<>ScoreDetail__5438|IFNG|0.000616077457010915__5417|IFNA1|0.000745162298178483__ 0 0 0 0 0 105984 16753239 137152 17034 9236 PPARG PPAR PPAR-G 7 1.9 Natarajan and Bright (2002) 2002 demonstrated that the PPAR-_amp_#x3b3 agonists 15d-PGJ 2 and ciglitazone decreased the severity of both 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105985 16753239 137152 22088 15934 TH1L TH1 Th1 29 0.0 and passive EAE presumably by suppressing IL-12 expression and associated Th1 cell differentiation 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105986 16753239 137154 17034 9236 PPARG PPAR PPAR-G 4 1.9 (2003) 2003 also demonstrated that PPAR-_amp_#x3b3 deficient heterozygous mice exhibit more severe EAE than wild-type mice 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105987 16753239 137155 17034 9236 PPARG PPAR PPAR-G 6 1.9 These studies cannot be performed in PPAR-_amp_#x3b3 homozygous knockout mice which die en utero suggesting that PPAR-_amp_#x3b3 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105988 16753239 137155 17034 9236 PPARG PPAR PPAR-G 16 1.9 PPAR-_amp_#x3b3 homozygous knockout mice which die en utero suggesting that PPAR-_amp_#x3b3 plays a critical role in development which cannot be compensated 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105989 16753239 137156 17034 9236 PPARG PPAR PPAR-G 8 1.9 Future studies utilizing inducible promoters to knock out PPAR-_amp_#x3b3 in adult mice are needed to confirm the role of 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105990 16753239 137158 17034 9236 PPARG PPAR PPAR-G 3 1.9 (2005) 2005 demonstrated that PPAR-_amp_#x3b3 antagonists exacerbate EAE 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105991 16753239 137159 17034 9236 PPARG PPAR PPAR-G 5 1.9 Collectively these studies suggest that PPAR-_amp_#x3b3 plays an important role in modulating the development of EAE 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105992 16753239 137162 17034 9236 PPARG PPAR PPAR-G 4 1.9 Interestingly this suggests that PPAR-_amp_#x3b3 and RXR ligands could act cooperatively in the treatment of 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105993 16753239 137162 17034 9236 PPARG PPAR PPAR-G 24 1.9 of MS A small clinical study supports the idea that PPAR-_amp_#x3b3 agonists may be effective in the treatment of MS ( 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105994 16753239 137163 17034 9236 PPARG PPAR PPAR-G 12 1.9 clinical trials are needed to assess the therapeutic potential of PPAR-_amp_#x3b3 agonists for the treatment of MS 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105995 16753239 137165 22088 15934 TH1L TH1 Th1 27 0.0 differentiation of T lymphocytes toward the T helper 1 (Th1) Th1 phenotype 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105996 16753239 137167 6327 15531 EBNA1BP2 p40 p40 23 0.3 EAE and MS We demonstrated that 15d-PGJ 2 suppresses IL-12 p40 production in both the mouse N9 microglial cell line and 1 JUMiner_v2.2 1 0 0 2 682 TotalCon:9<>682|ARHGEF2|9181|Complete__15531|EBNA1BP2|10969|Complete__9565|PSMD7|5713|Complete__6029|IL9|3578|Complete__6508|LANCL1|10314|No_GeneRif__6502|RPSA|3921|Complete__6871|MAPK1|5594|Complete__16896|RABEPK|10244|Complete__15979|TP63|8626|Complete__<>AvaiableGeneRif=8<>BEST:682|ARHGEF2|0.0010304951778643<>ScoreDetail__15979|TP63|0.000629059589589131__16896|RABEPK|0.000576121598430988__6502|RPSA|0.000530315737861447__15531|EBNA1BP2|0.000653755005311759__682|ARHGEF2|0.0010304951778643__9565|PSMD7|0.00016343875132794__6029|IL9|0.00071221120104219__6871|MAPK1|0.000977108762759342__ 0 0 0 0 0 105997 16753239 137168 22088 15934 TH1L TH1 Th1 19 0.0 progression by inhibiting IL-12 production by microglia which may inhibit Th1 cell differentiation 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105998 16753239 137169 3889 11919 CD40 CD40 CD40 13 0.6 cells (APCs) APCs including microglia can produce co-stimulatory molecules including CD40 CD80 and CD86 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 105999 16753239 137169 3908 1700 CD80 CD80 CD80 14 0.3 (APCs) APCs including microglia can produce co-stimulatory molecules including CD40 CD80 and CD86 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106000 16753239 137169 3914 1705 CD86 CD86 CD86 14 0.3 (APCs) APCs including microglia can produce co-stimulatory molecules including CD40 CD80 and CD86 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106001 16753239 137169 3914 1705 CD86 CD86 CD86 16 0.3 including microglia can produce co-stimulatory molecules including CD40 CD80 and CD86 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106002 16753239 137169 872 583 APC APC APCs 5 0.0 In addition antigen presenting cells (APCs) APCs including microglia can produce co-stimulatory molecules including CD40 CD80 and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106003 16753239 137170 3865 1678 CD4 CD4 CD4 18 0.3 cognate receptors plays a critical role in the differentiation of CD4 T cells which influence the development of EAE and MS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106004 16753239 137170 17034 9236 PPARG PPAR PPAR-G 34 1.9 the development of EAE and MS We demonstrated that the PPAR-_amp_#x3b3 agonist 15d-PGJ 2 selectively inhibits microglial expression of CD40 but 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106005 16753239 137170 3889 11919 CD40 CD40 CD40 43 0.6 the PPAR-_amp_#x3b3 agonist 15d-PGJ 2 selectively inhibits microglial expression of CD40 but not CD80 and CD86 co-stimulatory molecules 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106006 16753239 137170 3908 1700 CD80 CD80 CD80 46 0.3 15d-PGJ 2 selectively inhibits microglial expression of CD40 but not CD80 and CD86 co-stimulatory molecules 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106007 16753239 137170 3914 1705 CD86 CD86 CD86 46 0.3 15d-PGJ 2 selectively inhibits microglial expression of CD40 but not CD80 and CD86 co-stimulatory molecules 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106008 16753239 137170 3914 1705 CD86 CD86 CD86 48 0.3 selectively inhibits microglial expression of CD40 but not CD80 and CD86 co-stimulatory molecules 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106009 16753239 137170 872 583 APC APC APCs 5 0.0 Interaction of co-stimulatory molecules on APCs with their cognate receptors plays a critical role in the 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106010 16753239 137171 17034 9236 PPARG PPAR PPAR-G 3 1.9 This suggests that PPAR-_amp_#x3b3 agonists may modulate EAE in part by affecting microglia-T cell 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106011 16753239 137172 17034 9236 PPARG PPAR PPAR-G 6 1.9 The studies outlined above suggest that PPAR-_amp_#x3b3 agonists may inhibit EAE at least in part by blocking 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106012 16753239 137173 17034 9236 PPARG PPAR PPAR-G 26 1.9 an important role in initiating EAE and MS In fact PPAR-_amp_#x3b3 agonists likely modulate the development of these disorders by a 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106013 16753239 137175 17031 9232 PPARA PPAR PPAR-A 0 1.9 PPAR-_amp_#x3b1 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106014 16753239 137176 17031 9232 PPARA PPAR PPAR-A 3 1.9 The role of PPAR-_amp_#x3b1 agonists in MS has not been thoroughly investigated 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106015 16753239 137177 17031 9232 PPARA PPAR PPAR-A 4 1.9 We demonstrated that the PPAR-_amp_#x3b1 agonists gemfibrozil and fenofibrate inhibit the clinical signs of EAE 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106016 16753239 137178 17031 9232 PPARA PPAR PPAR-A 2 1.9 In fact PPAR-_amp_#x3b1 agonists in combination with the RXR agonist 9-cis RA act 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106017 16753239 137180 17033 9235 PPARD PPAR PPAR-B 0 1.9 PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106018 16753239 137182 17033 9235 PPARD PPAR PPAR-B 4 1.9 (2005) 2005 demonstrated that the PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 agonist GW0742 suppressed the development of EAE 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106019 16753239 137186 17031 9232 PPARA PPAR PPAR 6 1.9 In addition to effects on EAE PPAR agonists have been demonstrated to be effective in the treatment 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106020 16753239 137187 17034 9236 PPARG PPAR PPAR-G 2 1.9 For example PPAR-_amp_#x3b3 agonists were demonstrated to improve clinical outcomes in animal models 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106021 16753239 137187 16343 17468 PDLIM5 LIM Lim 21 0.3 in animal models of AD ( Heneka et al. 2005 Lim et al. 2000 and Yan et al. 2003 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 106022 16753239 137188 16343 17468 PDLIM5 LIM Lim 0 0.3 Lim et al 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 106023 16753239 137189 17034 9236 PPARG PPAR PPAR-G 7 1.9 (2000) 2000 demonstrated that Tg2576 mice fed the PPAR-_amp_#x3b3 agonist ibuprofen for 6 months beginning at an age of 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106024 16753239 137189 926 620 APP amyloid amyloid 21 1.0 6 months beginning at an age of 10 months when amyloid plaques first develop exhibited decreased glial activation amyloid deposition and 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 106025 16753239 137189 926 620 APP amyloid amyloid 29 1.0 months when amyloid plaques first develop exhibited decreased glial activation amyloid deposition and dystrophic neuritis relative to untreated animals 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 106026 16753239 137190 16343 17468 PDLIM5 LIM Lim 15 0.3 animal model of AD corroborated the in vivo observations of Lim et al 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 106027 16753239 137192 926 620 APP APP APP 8 0.3 In addition these studies demonstrated that ibuprofen altered APP processing resulting in decreased production of A_amp_#x3b2 42 in vitro 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106028 16753239 137193 17034 9236 PPARG PPAR PPAR-G 3 1.9 The role of PPAR-_amp_#x3b3 agonists in modulating the development of AD was further supported 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106029 16753239 137194 17034 9236 PPARG PPAR PPAR-G 5 1.9 Collectively these studies suggest that PPAR-_amp_#x3b3 agonists may be effective in the treatment of AD 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106030 16753239 137200 17034 9236 PPARG PPAR PPAR-G 11 1.9 dramatically inhibited glial activation in these studies suggesting that this PPAR-_amp_#x3b3 agonist may protect tyrosine hydroxylase positive neurons by controlling glial 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106031 16753239 137204 20996 11179 SOD1 ALS ALS 0 0.9 ALS is a fatal neurodegenerative disorder characterized by loss of motor 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000580796516805404<>ScoreDetail__5468|IGFALS|0.000384737206593143__11179|SOD1|0.000580796516805404__ 0 0 0 0 0 106032 16753239 137206 17034 9236 PPARG PPAR PPAR-G 5 1.9 Recent reports demonstrate that the PPAR-_amp_#x3b3 agonist pioglitazone protected motor neurons improved motor performance and extended 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106033 16753239 137206 20996 11179 SOD1 ALS ALS 28 0.9 of superoxide dismutase-1 G93A transgenic mice an animal model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000580796516805404<>ScoreDetail__5468|IGFALS|0.000384737206593143__11179|SOD1|0.000580796516805404__ 0 0 0 0 0 106034 16753239 137211 17031 9232 PPARA PPAR PPAR 3 1.9 The effects of PPAR agonists on stroke have recently been investigated 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106035 16753239 137212 17034 9236 PPARG PPAR PPAR-G 1 1.9 The PPAR-_amp_#x3b3 agonists troglitazone and pioglitazone reduced infarct volume and improved neurological 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106036 16753239 137213 17034 9236 PPARG PPAR PPAR-G 15 1.9 infarct volume was reduced and neurological function was improved by PPAR-_amp_#x3b3 agonist treatment when measured 22 days after the ischemic event 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106037 16753239 137216 17034 9236 PPARG PPAR PPAR-G 3 1.9 This suggests that PPAR-_amp_#x3b3 agonists may be therapeutic in humans following stroke 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106038 16753239 137218 17034 9236 PPARG PPAR PPAR-G 3 1.9 This suggests that PPAR-_amp_#x3b3 agonists may modulate events that occur following reperfusion 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106039 16753239 137219 17034 9236 PPARG PPAR PPAR-G 0 1.9 PPAR-_amp_#x3b3 agonists reduced CNS inflammation including macrophage/microglial macrophage microglial activation following 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106040 16753239 137221 17031 9232 PPARA PPAR PPAR-A 1 1.9 The PPAR-_amp_#x3b1 agonist fenofibrate reduced the susceptibility of apolipoprotein-E deficient mice to 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106041 16753239 137223 17031 9232 PPARA PPAR PPAR-A 1 1.9 Interestingly PPAR-_amp_#x3b1 knockout mice were not protected by fenofibrate supporting a role 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106042 16753239 137223 17031 9232 PPARA PPAR PPAR-A 13 1.9 mice were not protected by fenofibrate supporting a role for PPAR-_amp_#x3b1 in modulating pathologic events following ischemia 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106043 16753239 137225 17033 9235 PPARD PPAR PPAR-B 4 1.9 Finally the effects of PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 in modulating ischemia have recently been studied ( Arsenijevic 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106044 16753239 137226 17033 9235 PPARD PPAR PPAR-B 3 1.9 In these studies PPAR-_amp_#x3b2;/_amp_#x3b4; PPAR-_amp_#x3b2 _amp_#x3b4 knockout mice demonstrated increased infarct size and increased CNS 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106045 16753239 137231 17031 9232 PPARA PPAR PPAR 0 1.9 PPAR agonists inhibit glial cell activation which may protect neuronal cells 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106046 16753239 137232 20996 11179 SOD1 ALS ALS 26 0.9 neuroinflammatory and neurodegenerative disorders including MS Alzheimer's disease Parkinson's disease ALS and stroke 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000580796516805404<>ScoreDetail__5468|IGFALS|0.000384737206593143__11179|SOD1|0.000580796516805404__ 0 0 0 0 0 106047 16753239 137233 17034 9236 PPARG PPAR PPAR-G 0 1.9 PPAR-_amp_#x3b3 agonists of the thiazolidinedione class are currently prescribed for the 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106048 16753239 137233 17031 9232 PPARA PPAR PPAR-A 17 1.9 currently prescribed for the treatment of type II diabetes while PPAR-_amp_#x3b1 agonists including fibrates are commonly prescribed for hypertriglyceridemia 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106049 16753239 137234 17031 9232 PPARA PPAR PPAR 11 1.9 should facilitate future clinical trials evaluating the efficacy of these PPAR agonists in the treatment of these human disorders of the 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106050 16753239 137235 17031 9232 PPARA PPAR PPAR 7 1.9 Finally understanding the molecular mechanisms by which PPAR agonists regulate CNS inflammation will also be critical in developing 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106631 16766086 138231 9947 5468 IGFALS ALS ALS 34 0.3 stroke multiple sclerosis Parkinson's disease and amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131806371756415<>ScoreDetail__5468|IGFALS|0.000444303395747382__11179|SOD1|0.00131806371756415__ 0 0 0 0 0 106632 16766086 138237 17031 9232 PPARA PPAR PPARs 10 2.5 subfamily of nuclear receptors are the peroxisome proliferator-activated receptors (PPARs) PPARs which is comprised of three receptors PPAR_amp_#x3b1 _amp_#x3b2;/_amp_#x3b4; _amp_#x3b2 _amp_#x3b4 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106633 16766086 138246 9130 14065 HDAC9 HDAC HDACs 19 1.3 complexed with the nuclear corepressors and associated histone deacetylases (HDACs) HDACs ( Fig 1 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106634 16766086 138247 9130 14065 HDAC9 HDAC HDAC 14 1.3 keep the receptor in a repressed inactive state while the HDAC maintains the surrounding chromatin in a condensed state through histone 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106635 16766086 138251 4918 2348 CREBBP CBP CBP 3 0.6 Coactivator proteins like CBP and p300 act to positively regulate gene expression due to 1 JUMiner_v2.2 1 0 0 2 2348 TotalCon:4<>9936|OPN1LW|5956|Complete__2348|CREBBP|1387|Complete__30043|PAG1|55824|Complete__3287|EIF4E|1977|Complete__<>AvaiableGeneRif=4<>BEST:2348|CREBBP|0.000561799994523723<>ScoreDetail__9936|OPN1LW|0.000294521892794031__30043|PAG1|0.000382361755557163__3287|EIF4E|0.00043977505007703__2348|CREBBP|0.000561799994523723__ 0 0 0 0 0 106636 16766086 138251 6670 3373 EP300 p300 p300 5 1.3 Coactivator proteins like CBP and p300 act to positively regulate gene expression due to their intrinsic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106637 16766086 138256 7683 3796 FOS AP-1 AP-1 15 1.3 the transcriptional level through antagonizing the actions of NF_amp_#x3ba B AP-1 and STAT1 transcription factors ( Daynes and Jones 2002 1 JUMiner_v2.2 1 0 0 2 6204 TotalCon:5<>3796|FOS|2353|Complete__3797|FOSB|2354|Complete__6204|JUN|3725|Complete__6205|JUNB|3726|Complete__6206|JUND|3727|Complete__<>AvaiableGeneRif=5<>BEST:6204|JUN|0.000603361659933914<>ScoreDetail__3796|FOS|0.000600766049977874__3797|FOSB|0.000516172389432838__6205|JUNB|0.000602231333026601__6204|JUN|0.000603361659933914__6206|JUND|0.000574527790871884__ 0 0 0 0 0 106638 16766086 138256 21414 11362 STAT1 STAT1 STAT1 17 0.1 level through antagonizing the actions of NF_amp_#x3ba B AP-1 and STAT1 transcription factors ( Daynes and Jones 2002 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106639 16766086 138260 8569 16769 GORASP1 p65 p65 10 0.0 PPAR_amp_#x3b3 has also been shown to physically interact with the p65 subunit of NF_amp_#x3ba B blocking its ability to interact with 1 JUMiner_v2.2 1 0 0 2 16769 TotalCon:2<>16769|GORASP1|64689|Complete__11509|SYT1|6857|Complete__<>AvaiableGeneRif=2<>BEST:16769|GORASP1|0.000319481375234203<>ScoreDetail__16769|GORASP1|0.000319481375234203__11509|SYT1|0.000190114660956994__ 0 0 0 0 0 106640 16766086 138275 14535 7873 NOS2A iNOS iNOS 9 2.5 (1999) 1999 reported that PPAR_amp_#x3b3 agonists suppress cytokine evoked neuronal iNOS expression in vitro thereby preventing NO-mediated cell death of neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106641 16766086 138276 14535 7873 NOS2A iNOS iNOS 20 2.5 cerebellum resulted in induction of inducible nitric oxide synthase (iNOS) iNOS expression and subsequent neuronal death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106642 16766086 138277 14535 7873 NOS2A iNOS iNOS 22 2.5 it was argued to be due to the suppression of iNOS and other inflammatory gene expression ( Heneka et al. 2000 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106643 16766086 138280 14535 7873 NOS2A iNOS iNOS 9 2.5 However PPAR_amp_#x3b3 agonist treatment was shown to suppress neuronal iNOS expression ( Heneka et al. 1999 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106644 16766086 138285 926 620 APP amyloid amyloid 18 1.0 demonstrated in studies of hippocampal neurons challenged with neurotoxic beta amyloid (A_amp_#x3b2;) A_amp_#x3b2 peptides ( Inestrosa et al. 2005 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 106645 16766086 138297 17610 9605 PTGS2 COX-2 COX-2 7 1.0 These agents suppressed cytokine as well as COX-2 expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106646 16766086 138301 16343 17468 PDLIM5 LIM Lim 19 0.3 burden and reduce inflammation in animal models of AD ( Lim et al. 2000 and Lim et al. 2001 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 106647 16766086 138301 16343 17468 PDLIM5 LIM Lim 24 0.3 animal models of AD ( Lim et al. 2000 and Lim et al. 2001 2 JUMiner_v2.2 1 2 34 0 0 0 0 0 0 0 0 106648 16766086 138304 926 620 APP APP APP 10 0.3 1997 treated 1-year-old Tg2576 mice bearing a mutant form of APP (KM670/671NL) KM670 671NL for 4 months with oral pioglitazone or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106649 16766086 138311 926 620 APP APP hAPP 3 0.3 Mice overexpressing the hAPP V717I mutation were treated for 7 days with a higher 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106650 16766086 138322 926 620 APP APP APP 18 0.3 ability of inflammatory cyokines to stimulate the expression of the APP processing enzyme BACE1 ( Sastre et al. 2003 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106651 16766086 138322 1490 933 BACE1 BACE1 BACE1 21 0.5 cyokines to stimulate the expression of the APP processing enzyme BACE1 ( Sastre et al. 2003 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106652 16766086 138323 1490 933 BACE1 BACE1 BACE1 24 0.5 to the ability of this nuclear receptor to repress the BACE1 gene ( Sastre et al. 2006 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106653 16766086 138324 926 620 APP APP APP 14 0.3 reported that PPAR_amp_#x3b3 activation can lead to suppression of cellular APP levels through the stimulation of the ubiquitination and subsequent degradation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106654 16766086 138324 926 620 APP APP APP 26 0.3 through the stimulation of the ubiquitination and subsequent degradation of APP ( d_amp_#x2019 Abramo et al. 2005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106655 16766086 138329 926 620 APP APP APP 20 0.3 reduced A_amp_#x3b2 peptide levels and plaque burden observed in pioglitazone-treated APP overexpressing transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106656 16766086 138346 912 613 APOE APOE ApoE 9 0.0 Importantly the efficacy of drug treatment was related to ApoE genotype 14 JUMiner_v2.2 1 1 apoe; 0 0 0 0 0 0 0 0 106657 16766086 138359 14535 7873 NOS2A iNOS iNOS 6 2.5 Expression of inflammatory genes such as iNOS cyclooxygenase-2 (COX-2), COX-2 proinflammatory cytokines and intercellular adhesion molecule are 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106658 16766086 138359 17610 9605 PTGS2 COX-2 COX-2 8 1.0 Expression of inflammatory genes such as iNOS cyclooxygenase-2 (COX-2), COX-2 proinflammatory cytokines and intercellular adhesion molecule are upregulated following stroke 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106659 16766086 138367 14535 7873 NOS2A iNOS iNOS 21 2.5 is associated with reduced expression of inflammatory mediators such as iNOS COX-2 and IL-1_amp_#x3b2 ( Fig 5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106660 16766086 138367 17610 9605 PTGS2 COX-2 COX-2 22 1.0 associated with reduced expression of inflammatory mediators such as iNOS COX-2 and IL-1_amp_#x3b2 ( Fig 5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106661 16766086 138384 14535 7873 NOS2A iNOS iNOS 13 2.5 level troglitazone inhibited pro-inflammatory cytokine expression including IL1_amp_#x3b2 TNF_amp_#x3b1 and iNOS in the spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106662 16766086 138415 9947 5468 IGFALS ALS ALS 3 0.3 Amyotrophic lateral sclerosis (ALS) ALS is a fatal late onset and progressive neurodegenerative disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131806371756415<>ScoreDetail__5468|IGFALS|0.000444303395747382__11179|SOD1|0.00131806371756415__ 0 0 0 0 0 106663 16766086 138418 9947 5468 IGFALS ALS ALS 3 0.3 Animal models of ALS recapitulate the neuronal loss and glial activation that are central 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131806371756415<>ScoreDetail__5468|IGFALS|0.000444303395747382__11179|SOD1|0.00131806371756415__ 0 0 0 0 0 106664 16766086 138419 9947 5468 IGFALS ALS ALS 18 0.3 the PPAR_amp_#x3b3 agonist pioglitazone in two different murine models of ALS ( Kiaei et al. 2005 and Schutz et al. 2005 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131806371756415<>ScoreDetail__5468|IGFALS|0.000444303395747382__11179|SOD1|0.00131806371756415__ 0 0 0 0 0 106665 16766086 138421 9947 5468 IGFALS ALS ALS 6 0.3 Oral administration of pioglitazone to transgenic ALS mice resulted in a significant delay in loss of motor 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00131806371756415<>ScoreDetail__5468|IGFALS|0.000444303395747382__11179|SOD1|0.00131806371756415__ 0 0 0 0 0 106666 16766086 138455 14535 7873 NOS2A iNOS iNOS 14 2.5 vehicle treated rats mRNA was reduced by approximately 25% for iNOS 30% for COX-2 and 50% for IL-1_amp_#x3b2 ( n = 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 106667 16766086 138455 17610 9605 PTGS2 COX-2 COX-2 17 1.0 mRNA was reduced by approximately 25% for iNOS 30% for COX-2 and 50% for IL-1_amp_#x3b2 ( n = 4 for each 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107876 16781706 139905 20996 11179 SOD1 ALS ALS 6 2.4 Effective treatment for amyotrophic lateral sclerosis (ALS) ALS remains elusive 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107877 16781706 139906 20996 11179 SOD1 ALS ALS 8 2.4 Motor neuron degeneration is the primary pathology in ALS however non-neuronal cells contribute to the disease process 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107878 16781706 139909 20996 11179 SOD1 ALS ALS 23 2.4 disease progression when administered after onset of signs in an ALS mouse model (hSOD1 hSOD1 G93A transgenic mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107879 16781706 139909 20996 11179 SOD1 SOD1 hSOD1 26 2.7 after onset of signs in an ALS mouse model (hSOD1 hSOD1 G93A transgenic mice 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107880 16781706 139911 20996 11179 SOD1 ALS ALS 3 2.4 Three conditions of ALS the loss of motor function paralysis scoring and weight loss 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107881 16781706 139916 20996 11179 SOD1 ALS ALS 25 2.4 the basis for developing new drugs for the treatment of ALS and other chronic neurodegenerative diseases 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107882 16781706 139919 20996 11179 SOD1 ALS ALS 3 2.4 Amyotrophic lateral sclerosis (ALS) ALS is the third most common neurodegenerative cause of adult death 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107883 16781706 139920 20996 11179 SOD1 ALS ALS 0 2.4 ALS results in the degeneration of motor neurons in the cortex 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107884 16781706 139921 20996 11179 SOD1 ALS ALS 3 2.4 Most causes of ALS are presently unknown and several mechanisms of insult to motor 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107885 16781706 139923 6111 19199 DPPA3 Stella Stella 27 1.3 and neuroinflammation ( Carter and Rosen 2001 Pertwee 1999 and Stella 2004 ( Panikashvili et al. 2001 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 107886 16781706 139924 20996 11179 SOD1 ALS ALS 43 2.4 _amp_#x394 9 -THC slows progression and improves survival in the ALS mouse model ( hSOD1 G93A transgenic mice even when administered 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107887 16781706 139924 20996 11179 SOD1 SOD1 hSOD1 47 2.7 progression and improves survival in the ALS mouse model ( hSOD1 G93A transgenic mice even when administered after the onset of 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107888 16781706 139924 24058 12731 WAS THC THC 9 0.0 We have previously shown that the cannabinoid _amp_#x394 9 -THC (delta-9-tetrahydrocannabinol, delta-9-tetrahydrocannabinol which acts on cannabinoid CB 1 and CB 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107889 16781706 139924 24058 12731 WAS THC THC 35 0.0 oxidative damage in spinal cord cultures and that _amp_#x394 9 -THC slows progression and improves survival in the ALS mouse model 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107890 16781706 139926 926 620 APP amyloid amyloid 30 1.0 al. 2003 and cannabinoid CB 2 receptor activation blocks _amp_#x3b2 -amyloid induced microglial activation ( Ramirez et al. 2005 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 107891 16781706 139928 20996 11179 SOD1 SOD1 SOD1 5 2.9 Mutations in Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 are the primary cause of up to 20% of familial 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107892 16781706 139928 20996 11179 SOD1 ALS ALS 16 2.4 are the primary cause of up to 20% of familial ALS cases ( Rosen et al. 1993 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107893 16781706 139929 20996 11179 SOD1 SOD1 SOD1 4 2.9 Transgenic mice expressing human SOD1 mutations have been generated 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107894 16781706 139930 20996 11179 SOD1 SOD1 hSOD1 1 2.7 These hSOD1 mutant transgenic mice exhibit pathologic and cytological neuromuscular degeneration similar 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107895 16781706 139930 20996 11179 SOD1 ALS ALS 21 2.4 similar to patients with familial and some forms of sporadic ALS ( Bruijn et al. 1997 Gurney et al. 1994 and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107896 16781706 139931 20996 11179 SOD1 SOD1 hSOD1 1 2.7 The hSOD1 G93A mice are used for preclinical testing of compounds for 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107897 16781706 139931 20996 11179 SOD1 ALS ALS 13 2.4 mice are used for preclinical testing of compounds for treating ALS since the disease in these animals follows a consistent onset 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107898 16781706 139931 20996 11179 SOD1 ALS ALS 30 2.4 follows a consistent onset progression and outcome that mimics human ALS ( Gurney et al. 1996 Klivenyi et al. 1999 and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107899 16781706 139932 20996 11179 SOD1 SOD1 hSOD1 9 2.7 Here we report that AM1241 slows disease progression in hSOD1 G93A mice when administered after onset of disease signs 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107900 16781706 139937 20996 11179 SOD1 SOD1 SOD1 6 2.9 Male transgenic mice expressing the human SOD1 G93A (B6SJL-TgN[SOD1-G93A]1Gur) B6SJL-TgN SOD1-G93A 1Gur ( hSOD1 G93A mice were 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107901 16781706 139937 20996 11179 SOD1 SOD1 hSOD1 10 2.7 expressing the human SOD1 G93A (B6SJL-TgN[SOD1-G93A]1Gur) B6SJL-TgN SOD1-G93A 1Gur ( hSOD1 G93A mice were bred with background matched B6SJL wild type 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107902 16781706 139939 20996 11179 SOD1 SOD1 SOD1 13 2.9 genotyped using primers specific to exon 4 of the human SOD1 gene within the transgenic construct and segregated and used for 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107903 16781706 139945 20996 11179 SOD1 SOD1 hSOD1 0 2.7 hSOD1 G93A mice were injected intraperitoneally with vehicle (18:1:1 18 1 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107904 16781706 139972 12428 6923 MBNL1 EXP exp 0 0.0 Time=7(1+exp((Age_amp_#x2212; Time=7 1 exp Age_amp_#x2212 A )/ B _amp_#x2212 1 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107905 16781706 139990 20996 11179 SOD1 SOD1 hSOD1 13 2.7 here indicate that AM1241 delays progression of disease in male hSOD1 G93A mice when administered after onset of signs 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107906 16781706 139997 20996 11179 SOD1 SOD1 hSOD1 12 2.7 phytoestrogen delayed disease onset and mortality when given to male hSOD1 G93A mice reversing the sexual dimorphism normally seen in this 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107907 16781706 139997 20996 11179 SOD1 ALS ALS 25 2.4 reversing the sexual dimorphism normally seen in this strain of ALS mice ( Trieu and Uckun 1999 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00123539212442415<>ScoreDetail__5468|IGFALS|0.000334317713266841__11179|SOD1|0.00123539212442415__ 0 0 0 0 0 107908 16781706 139999 20996 11179 SOD1 SOD1 hSOD1 14 2.7 found to slow disease progression without ultimately affecting survival of hSOD1 G93A mice including cannabinol another cannabinoid compound ( Weydt et 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107909 16781706 140000 24058 12731 WAS THC THC 19 0.0 AM1241 may extend survival as was observed with _amp_#x394 9 -THC treatment where treatment with 5_amp_#xa0;mg/kg 5_amp_#xa0 mg kg did not 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107910 16781706 140004 20996 11179 SOD1 SOD1 hSOD1 2 2.7 Microglia from hSOD1 G93A mice possess increased cytotoxic potential ( Weydt et al. 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 107911 16781706 140005 926 620 APP amyloid amyloid 6 1.0 Cannabinoid CB 2 receptor activation blocks _amp_#x3b2 -amyloid induced microglial activation ( Ramirez et al. 2005 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 108709 16793728 140884 13686 7321 MSC MSC MSC 7 0.3 On the other hand mesenchymal stem cells (MSC) MSC from adult BM implanted in injured areas recover the morphology 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>7321|MSC|9242|Complete__29786|SLC25A37|51312|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 108710 16793728 140885 13686 7321 MSC MSC MSC 20 0.3 is a direct relationship between anti-nervous tissue T cells and MSC reparatory properties 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>7321|MSC|9242|Complete__29786|SLC25A37|51312|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 108711 16793728 140887 13686 7321 MSC MSC MSC 6 0.3 These cells were cocultured with autologous MSC for 2-15 days 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>7321|MSC|9242|Complete__29786|SLC25A37|51312|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 108712 16793728 140889 13686 7321 MSC MSC MSC 6 0.3 RESULTS After 48 h of coculture MSC adopted a spindle shape with polarization of the cytoplasm that 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>7321|MSC|9242|Complete__29786|SLC25A37|51312|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 108713 16793728 140893 8254 4235 GFAP GFAP GFAP 8 2.5 The differentiated cells reacted positively to tubuline III GFAP and nestin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 108714 16793728 140895 13686 7321 MSC MSC MSC 11 0.3 We observed that autoreactive cells may induce the transdifferentiation of MSC to neural stem cells 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>7321|MSC|9242|Complete__29786|SLC25A37|51312|No_GeneRif__<>AvaiableGeneRif=1<> 1 1 0 0 0 100182 16877542 128957 20996 11179 SOD1 ALS ALS 1 2.2 Abstract ALS is a fatal paralytic disorder characterized by a progressive loss 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100183 16877542 128958 20996 11179 SOD1 ALS ALS 20 2.2 species-producing enzyme during inflammation is activated in spinal cords of ALS patients and in spinal cords in a genetic animal model 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100184 16877542 128959 20996 11179 SOD1 ALS ALS 8 2.2 We demonstrate that inactivation of NADPH oxidase in ALS mice delays neurodegeneration and extends survival 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100185 16877542 128960 9939 5464 IGF1 IGF1 IGF1 16 2.0 products damage proteins such as insulin-like growth factor 1 (IGF1) IGF1 receptors which are located on motor neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100186 16877542 128961 9939 5464 IGF1 IGF1 IGF1 15 2.0 data indicate that such an oxidative modification hinders the IGF1/Akt IGF1 Akt survival pathway in motor neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100187 16877542 128961 543 391 AKT1 AKT Akt 15 0.3 indicate that such an oxidative modification hinders the IGF1/Akt IGF1 Akt survival pathway in motor neurons 4 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100188 16877542 128962 20996 11179 SOD1 ALS ALS 23 2.2 death and contribute to the selective motor neuronal degeneration in ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100189 16877542 128963 20996 11179 SOD1 ALS ALS 2 2.2 Keywords Akt ALS microglia oxidation non-cell autonomous 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100190 16877542 128963 543 391 AKT1 AKT Akt 1 0.2 Keywords Akt ALS microglia oxidation non-cell autonomous 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100191 16877542 128966 20996 11179 SOD1 SOD1 SOD1 1 2.2 Transgenic SOD1 G93A mice [C57BL/6J-TgN(SOD1-G93A)1Gur C57BL 6J-TgN SOD1-G93A 1Gur dl were crossed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100192 16877542 128969 20996 11179 SOD1 SOD1 SOD1 26 2.2 for details about the timeline of behavioral abnormalities in transgenic SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100193 16877542 128972 8118 4141 GAPDH GAPDH GAPDH 15 0.0 phox glial fibrillary acidic protein macrophage antigen complex 1 and GAPDH and PCR conditions are presented in Supporting Text 1 JUMiner_v2.2 1 1 gapdh; 0 0 0 0 0 0 0 0 100194 16877542 128986 18723 10261 ROS1 ROS ROS 4 0.0 In Situ Visualization of ROS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100195 16877542 128991 6327 15531 EBNA1BP2 P40 P-40 9 0.3 Supernatants of mouse spinal cord tissue homogenized in Nonidet P-40 buffer containing 50 mM DTT were collected and incubated (at 11 JUMiner_v2.2 1 2 nonidet 0 2 6871 TotalCon:9<>682|ARHGEF2|9181|Complete__15531|EBNA1BP2|10969|Complete__9565|PSMD7|5713|Complete__6029|IL9|3578|Complete__6508|LANCL1|10314|No_GeneRif__6502|RPSA|3921|Complete__6871|MAPK1|5594|Complete__16896|RABEPK|10244|Complete__15979|TP63|8626|Complete__<>AvaiableGeneRif=8<>BEST:6871|MAPK1|0.000752624094504684<>ScoreDetail__15979|TP63|0.000496127774993406__16896|RABEPK|0.000101282916948008__6502|RPSA|0.000521222028738287__15531|EBNA1BP2|0.000738701616486897__682|ARHGEF2|0.000595108664553268__9565|PSMD7|0.000248157574288567__6029|IL9|0.000644004922037618__6871|MAPK1|0.000752624094504684__ 0 0 0 0 0 100196 16877542 128999 20996 11179 SOD1 ALS ALS 29 2.2 60.5 _amp_#x000b1 10.2 years and 8.0 _amp_#x000b1 2.6 h respectively ALS group ( n = 6 60.5 _amp_#x000b1 4.2 years and 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100197 16877542 129000 20996 11179 SOD1 ALS ALS 2 2.2 For the ALS patients the mean duration of disease was 19.3 _amp_#x000b1 2.6 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100198 16877542 129006 9939 5464 IGF1 IGF1 IGF1 9 2.0 Phosphorylation of Akt and cell viability in response to IGF1 recombinant and to H 2 O 2 or activated BV2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100199 16877542 129006 543 391 AKT1 AKT Akt 2 0.0 Phosphorylation of Akt and cell viability in response to IGF1 recombinant and to 2 JUMiner_v2.2 1 1 akt; 0 0 0 0 0 0 0 0 100200 16877542 129014 20996 11179 SOD1 ALS ALS 9 2.2 NADPH Oxidase Is Up-Regulated in Inflamed Spinal Cords of ALS Mice 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100201 16877542 129015 20996 11179 SOD1 SOD1 SOD1 28 2.2 stages of the disease in transgenic mice expressing mutant human SOD1 with a substitution of glycine to alanine in position 93 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100202 16877542 129015 20996 11179 SOD1 SOD1 SOD1 39 2.2 a substitution of glycine to alanine in position 93 (SOD1 SOD1 G93A the most widely studied model of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100203 16877542 129015 20996 11179 SOD1 ALS ALS 48 2.2 93 (SOD1 SOD1 G93A the most widely studied model of ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100204 16877542 129016 20996 11179 SOD1 ALS ALS 17 2.2 cord which carries the brunt of the pathology in this ALS model was determined by analyzing its catalytic subunit gp91 phox 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100205 16877542 129017 20996 11179 SOD1 SOD1 SOD1 18 2.2 whole-tissue extracts of spinal cord rose over time in transgenic SOD1 G93A mice ( Fig 1 A B D and E 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100206 16877542 129018 20996 11179 SOD1 SOD1 SOD1 32 2.2 in membrane fractions of spinal cord extracts from symptomatic transgenic SOD1 G93A mice ( Fig 1 C indicating that this cytosolic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100207 16877542 129018 3884 1659 CD33 p67 p67 4 0.0 The levels of the p67 phox subunit that contains the NADPH-binding site of the NADPH 1 JUMiner_v2.2 1 0 0 2 1659 TotalCon:2<>1659|CD33|945|Complete__16672|METAP2|10988|Complete__<>AvaiableGeneRif=2<>BEST:1659|CD33|0.000776415125613499<>ScoreDetail__1659|CD33|0.000776415125613499__16672|METAP2|0.000718318559914951__ 0 0 0 0 0 100208 16877542 129020 20996 11179 SOD1 SOD1 SOD1 9 2.2 Histological evaluation of the spinal cord of symptomatic transgenic SOD1 G93A mice showed numerous gp91 phox -positive cells primarily in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100209 16877542 129023 20996 11179 SOD1 SOD1 SOD1 7 2.2 NADPH Oxidase Causes Protein Oxidation in Transgenic SOD1 G93A Mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100210 16877542 129024 20996 11179 SOD1 SOD1 SOD1 12 2.2 characterized the status of spinal cord NADPH oxidase in transgenic SOD1 G93A mice by probing for formation of ROS and evidence 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100211 16877542 129024 18723 10261 ROS1 ROS ROS 20 0.0 in transgenic SOD1 G93A mice by probing for formation of ROS and evidence of protein oxidation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100212 16877542 129025 18723 10261 ROS1 ROS ROS 7 0.0 In nontransgenic mice spinal cord production of ROS evidenced by the fluorescence emitted by ethidium the oxidation product 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100213 16877542 129026 20996 11179 SOD1 SOD1 SOD1 5 2.2 In contrast in symptomatic transgenic SOD1 G93A mice carrying the wild-type gp91 phox allele (SOD SOD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100214 16877542 129026 20996 11179 SOD1 SOD SOD 14 2.2 SOD1 G93A mice carrying the wild-type gp91 phox allele (SOD SOD G93A /gp91 gp91 phox spinal cord ethidium fluorescence was intense 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100215 16877542 129027 20996 11179 SOD1 SOD1 SOD1 3 2.2 In symptomatic transgenic SOD1 G93A mice carrying the nonfunctional mutant allele (SOD SOD G93A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100216 16877542 129027 20996 11179 SOD1 SOD SOD 11 2.2 transgenic SOD1 G93A mice carrying the nonfunctional mutant allele (SOD SOD G93A /gp91 gp91 phox_amp_#x02212 ( 12 spinal cord ethidium fluorescence 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100217 16877542 129029 20996 11179 SOD1 SOD1 SOD1 2 2.2 Symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice but not age-matched SOD1 G93A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100218 16877542 129029 20996 11179 SOD1 SOD1 SOD1 10 2.2 transgenic SOD1 G93A /gp91 gp91 phox mice but not age-matched SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice had increased levels of spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100219 16877542 129030 20996 11179 SOD1 SOD1 SOD1 15 2.2 for protein carbonyl adducts occurred in spinal cord sections from SOD1 G93A /gp91 gp91 phox mice at the level of cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100220 16877542 129031 20996 11179 SOD1 ALS ALS 9 2.2 NADPH Oxidase Induction and Neuronal Protein Carbonylation in Sporadic ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100221 16877542 129032 20996 11179 SOD1 SOD1 SOD1 13 2.2 to determine whether the NADPH oxidase alterations identified in transgenic SOD1 G93A mice were also present in human sporadic ALS the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100222 16877542 129032 20996 11179 SOD1 ALS ALS 22 2.2 transgenic SOD1 G93A mice were also present in human sporadic ALS the most common form of the disease ( 1 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100223 16877542 129033 20996 11179 SOD1 ALS ALS 45 2.2 was _amp_#x02248 3-fold higher and its immunoreactivity robust in sporadic ALS spinal cords ( Fig 2 E 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100224 16877542 129034 3901 1693 CD68 CD68 CD68 12 0.3 latter gp91 phox -positive cells colocalized with the microglial-associated antigen CD68 ( Fig 2 F and were identified in all of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100225 16877542 129034 20996 11179 SOD1 ALS ALS 26 2.2 2 F and were identified in all of the typical ALS loci of neurodegeneration including the anterior horn and the lateral 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100226 16877542 129035 20996 11179 SOD1 ALS ALS 22 2.2 protein carbonyl adducts in postmortem spinal cord sections from sporadic ALS cases which seemed to be mainly associated with large motor 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100227 16877542 129036 20996 11179 SOD1 ALS ALS 20 2.2 for protein carbonyl adducts per lumbar spinal cord section in ALS patients whereas no such immunoreactive motor neurons were seen in 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100228 16877542 129038 20996 11179 SOD1 SOD1 SOD1 10 2.2 Deletion of gp91 phox Mitigates the Disease Phenotype in Transgenic SOD1 G93A Mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100229 16877542 129039 20996 11179 SOD1 SOD1 SOD1 15 2.2 of NADPH oxidase activation on the disease phenotype in the SOD1 G93A mouse model of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100230 16877542 129039 20996 11179 SOD1 ALS ALS 20 2.2 the disease phenotype in the SOD1 G93A mouse model of ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100231 16877542 129040 20996 11179 SOD1 SOD1 SOD1 1 2.2 Transgenic SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice reached end-stage paralysis (defined defined 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100232 16877542 129040 20996 11179 SOD1 SOD1 SOD1 21 2.2 a loss of the righting reflex later than their transgenic SOD1 G93A /gp91 gp91 phox counterparts ( Fig 3 A which 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100233 16877542 129040 20996 11179 SOD1 SOD1 SOD1 39 2.2 3 A which resulted in a longer lifespan of transgenic SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice (log-rank log-rank test = 15.3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100234 16877542 129042 20996 11179 SOD1 SOD1 SOD1 4 2.2 Compared with end-stage transgenic SOD1 G93A /gp91 gp91 phox mice age-matched transgenic SOD1 G93A /gp91 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100235 16877542 129042 20996 11179 SOD1 SOD1 SOD1 11 2.2 end-stage transgenic SOD1 G93A /gp91 gp91 phox mice age-matched transgenic SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice had _amp_#x02248 50% more anterior 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100236 16877542 129043 20996 11179 SOD1 SOD1 SOD1 23 2.2 the glial cytokine IL-1_amp_#x003b2 did not differ between age-matched transgenic SOD1 G93A /gp91 gp91 phox mice and SOD1 G93A /gp91 gp91 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100237 16877542 129043 20996 11179 SOD1 SOD1 SOD1 29 2.2 between age-matched transgenic SOD1 G93A /gp91 gp91 phox mice and SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice (Fig Fig 7 which is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100238 16877542 129044 20996 11179 SOD1 SOD1 SOD1 14 2.2 the deficit of gp91 phox were the levels of human SOD1 in transgenic SOD1 G93A mice (Fig Fig 7 or the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100239 16877542 129044 20996 11179 SOD1 SOD1 SOD1 17 2.2 gp91 phox were the levels of human SOD1 in transgenic SOD1 G93A mice (Fig Fig 7 or the size of muscle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100240 16877542 129045 13956 23212 MYH14 myosin myosin 13 2.2 are mainly composed of fast-twitch fibers and by immunostaining for myosin heavy chain we did not observe any obvious alteration in 1 JUMiner_v2.2 1 0 0 2 7605 TotalCon:8<>23212|MYH14|79784|Complete__7599|MYO1E|4643|Complete__7600|MYO1F|4542|No_GeneRif__7603|MYO5B|4645|Complete__7604|MYO5C|55930|No_GeneRif__7605|MYO6|4646|Complete__7608|MYO9A|4649|No_GeneRif__7609|MYO9B|4650|Complete__<>AvaiableGeneRif=5<>BEST:7605|MYO6|0.000485207943838029<>ScoreDetail__7599|MYO1E|0.000437642233725961__7609|MYO9B|0.000474981955342383__7603|MYO5B|0.000320296404023615__23212|MYH14|0.000153049741165879__7605|MYO6|0.000485207943838029__ 0 0 0 0 0 100241 16877542 129047 9939 5464 IGF1 IGF1 IGF1 8 2.0 NADPH Oxidase Impairs the Insulin-Like Growth Factor 1 (IGF1)/Akt IGF1 Akt Pathway in Transgenic SOD1 G93A Mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100242 16877542 129047 20996 11179 SOD1 SOD1 SOD1 12 2.2 Insulin-Like Growth Factor 1 (IGF1)/Akt IGF1 Akt Pathway in Transgenic SOD1 G93A Mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100243 16877542 129047 543 391 AKT1 AKT Akt 8 0.3 NADPH Oxidase Impairs the Insulin-Like Growth Factor 1 (IGF1)/Akt IGF1 Akt Pathway in Transgenic SOD1 G93A Mice 4 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100244 16877542 129048 20996 11179 SOD1 ALS ALS 12 2.2 explored whether NADPH oxidase-mediated protein modifications might promote neurodegeneration in ALS by damaging essential surviving pathways for motor neurons such as 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100245 16877542 129048 9939 5464 IGF1 IGF1 IGF1 23 2.0 by damaging essential surviving pathways for motor neurons such as IGF1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100246 16877542 129049 9939 5464 IGF1 IGF1 IGF1 1 2.0 After IGF1 was immunoprecipitated from spinal cord extracts it was probed for 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100247 16877542 129050 9939 5464 IGF1 IGF1 IGF1 7 2.0 This approach failed to reveal evidence of IGF1 oxidation in any of the studied mouse genotypes (data data 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100248 16877542 129051 9939 5464 IGF1 IGF1 IGF1 11 2.0 carbonyl adducts were evident in the _amp_#x003b1 -chain of the IGF1 tyrosine kinase cognate receptor in the spinal cord of symptomatic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100249 16877542 129051 20996 11179 SOD1 SOD1 SOD1 23 2.2 kinase cognate receptor in the spinal cord of symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice ( Fig 4 A and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100250 16877542 129051 9939 5464 IGF1 IGF1 IGF1 43 2.0 B similar results were obtained for the _amp_#x003b2 -chain of IGF1 receptor (data data not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100251 16877542 129052 9939 5464 IGF1 IGF1 IGF1 7 2.0 This finding might be quite significant because IGF1 receptors in mouse spinal cords were detected almost exclusively on 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100252 16877542 129053 9939 5464 IGF1 IGF1 IGF1 3 2.0 Contrasting with the IGF1 receptor findings oxidation indices in the intracellular serine/threonine serine threonine 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100253 16877542 129053 9939 5464 IGF1 IGF1 IGF1 16 2.0 in the intracellular serine/threonine serine threonine kinase Akt which transduces IGF1 receptor signaling ( 15 did not differ between symptomatic transgenic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100254 16877542 129053 20996 11179 SOD1 SOD1 SOD1 28 2.2 receptor signaling ( 15 did not differ between symptomatic transgenic SOD1 G93A mice and their nontransgenic littermates 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100255 16877542 129053 543 391 AKT1 AKT Akt 13 0.0 findings oxidation indices in the intracellular serine/threonine serine threonine kinase Akt which transduces IGF1 receptor signaling ( 15 did not differ 2 JUMiner_v2.2 1 1 akt; 0 0 0 0 0 0 0 0 100256 16877542 129054 9939 5464 IGF1 IGF1 IGF1 6 2.0 These results suggest that the entire IGF1 molecular pathway is not oxidatively modified by inflammation in this 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100257 16877542 129054 20996 11179 SOD1 ALS ALS 17 2.2 molecular pathway is not oxidatively modified by inflammation in this ALS model 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100258 16877542 129056 9939 5464 IGF1 IGF1 IGF1 4 2.0 Next we compared selected IGF1 transduction events among the different mouse groups 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100259 16877542 129057 20996 11179 SOD1 SOD1 SOD1 2 2.2 Although mutant SOD1 is expressed in all cells markers of IGF1 transduction such 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100260 16877542 129057 9939 5464 IGF1 IGF1 IGF1 10 2.0 Although mutant SOD1 is expressed in all cells markers of IGF1 transduction such as phospho-IGF1 receptor phospho-Akt (data data not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100261 16877542 129057 20996 11179 SOD1 SOD1 SOD1 52 2.2 smaller glia-like cells in spinal cord sections of symptomatic transgenic SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100262 16877542 129058 20996 11179 SOD1 SOD1 SOD1 14 2.2 phospho-IGF1 receptor-immunoreactive cells in spinal cord sections from symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice than from age-matched SOD1 G93A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100263 16877542 129058 20996 11179 SOD1 SOD1 SOD1 22 2.2 transgenic SOD1 G93A /gp91 gp91 phox mice than from age-matched SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice ( Fig 4 C _amp_#x02013 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100264 16877542 129059 1494 936 BAD BAD BAD 39 0.3 ( Fig 4 H _amp_#x02013 J and smaller phospho-BAD total BAD ratios ( Fig 4 K and L in symptomatic transgenic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100265 16877542 129059 20996 11179 SOD1 SOD1 SOD1 51 2.2 ratios ( Fig 4 K and L in symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice compared with their age-matched SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100266 16877542 129059 20996 11179 SOD1 SOD1 SOD1 60 2.2 SOD1 G93A /gp91 gp91 phox mice compared with their age-matched SOD1 G93A /gp91 gp91 phox_amp_#x02212 counterparts 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100267 16877542 129059 543 391 AKT1 AKT Akt 5 0.0 There were also smaller phospho-Akt total Akt ratios ( Fig 4 F and G as well as 2 JUMiner_v2.2 1 1 akt; 0 0 0 0 0 0 0 0 100268 16877542 129059 543 391 AKT1 AKT Akt 27 0.0 fewer cells that were immunoreactive for a downstream target of Akt phospho-BAD ( Fig 4 H _amp_#x02013 J and smaller phospho-BAD 2 JUMiner_v2.2 1 1 akt; 0 0 0 0 0 0 0 0 100269 16877542 129060 9939 5464 IGF1 IGF1 IGF1 10 2.0 These data further support the idea that oxidative modification of IGF1 receptor in symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100270 16877542 129060 20996 11179 SOD1 SOD1 SOD1 15 2.2 idea that oxidative modification of IGF1 receptor in symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice is associated with a range 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100271 16877542 129061 9939 5464 IGF1 IGF1 IGF1 4 2.0 Microglial-Derived ROS Recapitulate the IGF1/Akt IGF1 Akt Pathway Defect in Vitro 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100272 16877542 129061 18723 10261 ROS1 ROS ROS 1 0.0 Microglial-Derived ROS Recapitulate the IGF1/Akt IGF1 Akt Pathway Defect in Vitro 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100273 16877542 129061 543 391 AKT1 AKT Akt 4 0.3 Microglial-Derived ROS Recapitulate the IGF1/Akt IGF1 Akt Pathway Defect in Vitro 4 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100274 16877542 129062 9939 5464 IGF1 IGF1 IGF1 10 2.0 To test the idea that NADPH oxidase-derived ROS could impair IGF1 pathway function an in vitro cell system using the neuron-like 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100275 16877542 129062 18723 10261 ROS1 ROS ROS 7 0.0 To test the idea that NADPH oxidase-derived ROS could impair IGF1 pathway function an in vitro cell system 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100276 16877542 129063 9939 5464 IGF1 IGF1 IGF1 10 2.0 were briefly incubated with 0.1_amp_#x02013 100 _amp_#x003bc M human recombinant IGF1 in the presence of overnight-preconditioned serum-free medium supplemented with or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100277 16877542 129063 9939 5464 IGF1 IGF1 IGF1 37 2.0 to provide a constant flux of H 2 O 2 IGF1 pathway responsiveness was monitored by Akt phosphorylation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100278 16877542 129063 543 391 AKT1 AKT Akt 43 0.0 H 2 O 2 IGF1 pathway responsiveness was monitored by Akt phosphorylation 2 JUMiner_v2.2 1 1 akt; 0 0 0 0 0 0 0 0 100279 16877542 129064 9939 5464 IGF1 IGF1 IGF1 2 2.0 Exposure to IGF1 caused a dose-dependent phosphorylation of Akt in SH-SY5Y cells ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100280 16877542 129064 543 391 AKT1 AKT Akt 8 0.0 Exposure to IGF1 caused a dose-dependent phosphorylation of Akt in SH-SY5Y cells ( Fig 5 A and B and 2 JUMiner_v2.2 1 1 akt; 0 0 0 0 0 0 0 0 100281 16877542 129065 9939 5464 IGF1 IGF1 IGF1 1 2.0 Conversely IGF1 barely increased Akt phosphorylation in the neuroblastoma cell lines that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100282 16877542 129065 543 391 AKT1 AKT Akt 4 0.0 Conversely IGF1 barely increased Akt phosphorylation in the neuroblastoma cell lines that were exposed to 2 JUMiner_v2.2 1 1 akt; 0 0 0 0 0 0 0 0 100283 16877542 129066 24053 12728 VWS LPS LPS-activated 11 0.0 SH-SY5Y cells were incubated with or without conditioned medium from LPS-activated BV2 microglial cells 11 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 100284 16877542 129067 9939 5464 IGF1 IGF1 IGF1-mediated 27 1.5 of H 2 O 2 ( Fig 5 E attenuated IGF1-mediated Akt phosphorylation in the neuroblastoma cell line ( Fig 5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100285 16877542 129067 24053 12728 VWS LPS LPS-activated 9 0.0 Akin to the glucose oxidase experiments brief exposure to LPS-activated microglial-conditioned medium which contained increased levels of H 2 O 11 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 100286 16877542 129067 543 391 AKT1 AKT Akt 28 0.2 H 2 O 2 ( Fig 5 E attenuated IGF1-mediated Akt phosphorylation in the neuroblastoma cell line ( Fig 5 C 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100287 16877542 129068 9939 5464 IGF1 IGF1 IGF1 13 2.0 to LPS-activated microglial-conditioned medium the Akt phosphorylation response to the IGF1 recombinant remained depressed and at 72 h a reduction of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100288 16877542 129068 9939 5464 IGF1 IGF1 IGF1 31 2.0 a reduction of cell viability indistinguishable from the condition without IGF1 was observed ( Fig 5 F 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100289 16877542 129068 24053 12728 VWS LPS LPS-activated 4 0.0 Upon longer exposure to LPS-activated microglial-conditioned medium the Akt phosphorylation response to the IGF1 recombinant 11 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 100290 16877542 129068 543 391 AKT1 AKT Akt 8 0.0 Upon longer exposure to LPS-activated microglial-conditioned medium the Akt phosphorylation response to the IGF1 recombinant remained depressed and at 2 JUMiner_v2.2 1 1 akt; 0 0 0 0 0 0 0 0 100291 16877542 129069 9939 5464 IGF1 IGF1 IGF1-mediated 5 1.5 However both the alteration of IGF1-mediated Akt phosphorylation and the loss of cell viability mediated by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100292 16877542 129069 543 391 AKT1 AKT Akt 6 0.2 However both the alteration of IGF1-mediated Akt phosphorylation and the loss of cell viability mediated by LPS-activated 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100293 16877542 129069 24053 12728 VWS LPS LPS-activated 16 0.0 Akt phosphorylation and the loss of cell viability mediated by LPS-activated microglia were counteracted by the specific NADPH oxidase inhibitor apocynin 11 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 100294 16877542 129072 20996 11179 SOD1 ALS ALS 6 2.2 Experimental evidence supports a model for ALS neurodegeneration in which nonneuronal cells such as microglia contribute to 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100295 16877542 129074 18723 10261 ROS1 ROS ROS 40 0.0 morphology of resting microglia and did not seem to produce ROS ( Figs 1 and 6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100296 16877542 129075 20996 11179 SOD1 SOD1 SOD1 3 2.2 Conversely in transgenic SOD1 G93A mice paralleling the worsening of the ALS phenotype there 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100297 16877542 129075 20996 11179 SOD1 ALS ALS 11 2.2 in transgenic SOD1 G93A mice paralleling the worsening of the ALS phenotype there was an intensification of spinal cord microgliosis accompanied 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100298 16877542 129076 20996 11179 SOD1 ALS ALS 30 2.2 of oxidatively damaging nearby macromolecules and cells homed within inflamed ALS tissues 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100299 16877542 129077 20996 11179 SOD1 SOD1 SOD1 20 2.2 were markedly elevated in spinal cord extracts of symptomatic transgenic SOD1 G93A mice for the most part in a NADPH oxidase-dependent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100300 16877542 129078 20996 11179 SOD1 ALS ALS 19 2.2 was also found in postmortem spinal cords from human sporadic ALS cases ( Fig 2 supporting the conclusion that the occurrence 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100301 16877542 129078 20996 11179 SOD1 ALS ALS 40 2.2 occurrence of inflammation-mediated oxidative damage is not restricted to familial ALS caused by SOD1 mutations but is also a pathological hallmark 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100302 16877542 129078 20996 11179 SOD1 SOD1 SOD1 43 2.2 oxidative damage is not restricted to familial ALS caused by SOD1 mutations but is also a pathological hallmark of the prevalent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100303 16877542 129078 20996 11179 SOD1 ALS ALS 58 2.2 a pathological hallmark of the prevalent nonfamilial sporadic form of ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100304 16877542 129079 20996 11179 SOD1 SOD1 SOD1 16 2.2 of the gp91 phox subunit of NADPH oxidase in transgenic SOD1 G93A mice eliminates the production of microglial-derived ROS ( Fig 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100305 16877542 129079 20996 11179 SOD1 ALS ALS 39 2.2 M and importantly prolongs survival and retards neurodegeneration in this ALS model ( Fig 3 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100306 16877542 129079 18723 10261 ROS1 ROS ROS 24 0.0 in transgenic SOD1 G93A mice eliminates the production of microglial-derived ROS ( Fig 1 M and importantly prolongs survival and retards 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100307 16877542 129080 20996 11179 SOD1 SOD1 SOD1 6 2.2 Deletion of gp91 phox in transgenic SOD1 G93A mice did not alter the spinal cord microglial response 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100308 16877542 129080 20996 11179 SOD1 SOD1 SOD1 22 2.2 the spinal cord microglial response or the expression of human SOD1 in transgenic SOD1 G93A mice (Fig Fig 7 which is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100309 16877542 129080 20996 11179 SOD1 SOD1 SOD1 25 2.2 microglial response or the expression of human SOD1 in transgenic SOD1 G93A mice (Fig Fig 7 which is a known determinant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100310 16877542 129080 20996 11179 SOD1 ALS ALS 40 2.2 which is a known determinant of disease severity in this ALS model ( 18 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100311 16877542 129081 20996 11179 SOD1 SOD1 SOD1 7 2.2 Consequently the attenuated phenotype seen in transgenic SOD1 G93A /gp91 gp91 phox_amp_#x02212 mice is attributable to the lack 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100312 16877542 129081 20996 11179 SOD1 SOD1 SOD1 34 2.2 either an impaired microglial response or expression of the human SOD1 G93A transgene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100313 16877542 129082 20996 11179 SOD1 ALS ALS 16 2.2 NADPH oxidase contributes to the degeneration of motor neurons in ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100314 16877542 129083 20996 11179 SOD1 ALS ALS 19 2.2 in the pathogenesis of chronic noninfectious pathological conditions such as ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100315 16877542 129084 20996 11179 SOD1 SOD1 SOD1 12 2.2 magnitude of benefit afforded by gp91 phox deletion in transgenic SOD1 G93A mice argues that targeting neuroinflammation by inhibiting just one 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100316 16877542 129084 20996 11179 SOD1 ALS ALS 41 2.2 not be sufficient to produce robust and lasting neuroprotection in ALS patients 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100317 16877542 129085 18723 10261 ROS1 ROS ROS 28 0.0 their plasma membrane proteins and lipids damaged by NADPH oxidase-derived ROS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100318 16877542 129086 20996 11179 SOD1 ALS ALS 5 2.2 However the chronic nature of ALS suggests that neuroinflammation is likely protracted and not as strong 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100319 16877542 129087 20996 11179 SOD1 ALS ALS 29 2.2 oxidative stress with the selective demise of motor neurons in ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100320 16877542 129088 20996 11179 SOD1 ALS ALS 30 2.2 of those already compromised as motor neurons probably are in ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100321 16877542 129088 18723 10261 ROS1 ROS ROS 6 0.0 First at that lower level of ROS production oxidative stress may not kill cells but instead may 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100322 16877542 129090 9939 5464 IGF1 IGF1 IGF1 9 2.0 Relevant to the latter scenario are our results for IGF1 a trophic factor that is known to promote motor neuron 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100323 16877542 129091 9939 5464 IGF1 IGF1 IGF1 9 2.0 In this study we indeed found that receptors for IGF1 were primarily expressed on motor neurons in mouse spinal cords 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100324 16877542 129091 9939 5464 IGF1 IGF1 IGF1 25 2.0 in mouse spinal cords (Fig Fig 8 and that the IGF1 signaling pathway was impaired by a NADPH oxidase-dependent mechanism in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100325 16877542 129091 20996 11179 SOD1 SOD1 SOD1 38 2.2 was impaired by a NADPH oxidase-dependent mechanism in symptomatic transgenic SOD1 G93A mice ( Fig 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100326 16877542 129092 9939 5464 IGF1 IGF1 IGF1 1 2.0 Although IGF1 per se did not seem to be damaged by inflammation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100327 16877542 129092 9939 5464 IGF1 IGF1 IGF1 20 2.0 by inflammation NADPH oxidase did stimulate the oxidative modification of IGF1 receptors ( Fig 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100328 16877542 129093 9939 5464 IGF1 IGF1 IGF1 5 2.0 The ligand-dependent kinase activation of IGF1 receptor relies on its arrangement into a heterotetrameric 2_amp_#x003b1;/2_amp_#x003b2;-chain 2_amp_#x003b1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100329 16877542 129094 9939 5464 IGF1 IGF1 IGF1 9 2.0 It may thus be predicted that oxidation of the IGF1 receptor main extracellular domains (i.e., i.e. the _amp_#x003b1 -chains could 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100330 16877542 129095 9939 5464 IGF1 IGF1 IGF1 28 2.0 molecular events that are normally elicited by ligation of the IGF1 receptor including autophosphorylation and Akt phosphorylation were indeed abated by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100331 16877542 129095 543 391 AKT1 AKT Akt 33 0.0 elicited by ligation of the IGF1 receptor including autophosphorylation and Akt phosphorylation were indeed abated by ROS in a microglial NADPH 2 JUMiner_v2.2 1 1 akt; 0 0 0 0 0 0 0 0 100332 16877542 129095 18723 10261 ROS1 ROS ROS 39 0.0 receptor including autophosphorylation and Akt phosphorylation were indeed abated by ROS in a microglial NADPH oxidase-dependent manner 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100333 16877542 129096 9939 5464 IGF1 IGF1 IGF1 11 2.0 data also show that microglial NADPH oxidase by impairing the IGF1 signaling pathway renders SH-SY5Y cells in our in vitro system 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100334 16877542 129096 24053 12728 VWS LPS LPS-activated 37 0.0 exposure to a hostile environment such as that emulated by LPS-activated microglial-conditioned medium ( Fig 5 11 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 100335 16877542 129097 20996 11179 SOD1 SOD1 SOD1 33 2.2 to withstand the toxicity of etiologic agents such as mutant SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100336 16877542 129098 9939 5464 IGF1 IGF1 IGF1 3 2.0 Muscle-specific expression of IGF1 stabilizes neuromuscular junctions reduces inflammation in the spinal cord and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100337 16877542 129098 20996 11179 SOD1 SOD1 SOD1 20 2.2 the spinal cord and enhances motor neuronal survival in transgenic SOD1 G93A mice ( 23 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100338 16877542 129099 9939 5464 IGF1 IGF1 IGF1 15 2.0 did not find any evidence that the rescue of the IGF1 pathway by abrogating NADPH oxidase was associated with muscle hypertrophy 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100339 16877542 129100 20996 11179 SOD1 SOD1 SOD1 3 2.2 Nevertheless whether transgenic SOD1 G93A mice carrying the gp91 phox null mutation reach end-stage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100340 16877542 129101 20996 11179 SOD1 SOD1 SOD1 3 2.2 Injection of transgenic SOD1 G93A mice with an adeno-associated virus carrying an IGF1 gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100341 16877542 129101 9939 5464 IGF1 IGF1 IGF1 12 2.0 transgenic SOD1 G93A mice with an adeno-associated virus carrying an IGF1 gene prolongs survival in these animals ( 20 24 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100342 16877542 129102 9939 5464 IGF1 IGF1 IGF1 23 2.0 but instead may blunt the motor neuron survival response to IGF1 in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100343 16877542 129102 20996 11179 SOD1 ALS ALS 25 2.2 may blunt the motor neuron survival response to IGF1 in ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100344 16877542 129103 20996 11179 SOD1 ALS ALS 5 2.2 Perhaps the modest change in ALS progression that is seen in patients treated with human recombinant 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100345 16877542 129103 9939 5464 IGF1 IGF1 IGF1 16 2.0 progression that is seen in patients treated with human recombinant IGF1 ( 25 may be related to the issue raised above 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100346 16877542 129104 9939 5464 IGF1 IGF1 IGF1 10 2.0 It may thus be argued that optimal therapeutic response to IGF1 in diseases such as ALS may rely on a concomitant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100347 16877542 129104 20996 11179 SOD1 ALS ALS 15 2.2 that optimal therapeutic response to IGF1 in diseases such as ALS may rely on a concomitant administration of this trophic factor 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100348 16877542 129114 20996 11179 SOD1 SOD1 SOD1 12 2.2 oxidase stimulates carbonylation of spinal cord motor neurons in transgenic SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100349 16877542 129115 20996 11179 SOD1 SOD1 SOD1 29 2.2 E in 1-month-old (asymptomatic) asymptomatic to 4-month-old (end-stage) end-stage transgenic SOD1 (more more ... 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100350 16877542 129117 20996 11179 SOD1 ALS ALS 16 2.2 with motor neuron carbonylation in the spinal cord of sporadic ALS patients 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100351 16877542 129118 20996 11179 SOD1 ALS ALS 23 2.2 spinal cord extracts from six normal controls and six age-matched ALS patients 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100352 16877542 129121 20996 11179 SOD1 SOD1 SOD1 11 2.2 of gp91 phox increases lifespan and lessens neurodegeneration in transgenic SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100353 16877542 129122 20996 11179 SOD1 SOD1 SOD1 7 2.2 ( A Survival comparison of transgenic SOD1 G93A /gp91 gp91 phox mice (red) red (122.0 122.0 _amp_#x000b1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100354 16877542 129122 20996 11179 SOD1 SOD1 SOD1 22 2.2 (122.0 122.0 _amp_#x000b1 1.7 days n = 19 and transgenic SOD1 G93A /gp91 gp91 phox_amp_#x02212 littermates (more more ... 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100355 16877542 129124 9939 5464 IGF1 IGF1 IGF1 3 2.0 Modulation of the IGF1/Akt IGF1 Akt pathway by NADPH oxidase-derived ROS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100356 16877542 129124 543 391 AKT1 AKT Akt 3 0.3 Modulation of the IGF1/Akt IGF1 Akt pathway by NADPH oxidase-derived ROS 4 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100357 16877542 129124 18723 10261 ROS1 ROS ROS 8 0.0 Modulation of the IGF1/Akt IGF1 Akt pathway by NADPH oxidase-derived ROS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100358 16877542 129125 9939 5464 IGF1 IGF1 IGF1 5 2.0 ( A Immunoprecipitation of IGF1 receptor _amp_#x003b1 -chain followed by OxyBlot (upper upper blot and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100359 16877542 129125 9939 5464 IGF1 IGF1 IGF1 18 2.0 by OxyBlot (upper upper blot and immunoblot for spinal cord IGF1 receptor _amp_#x003b1 -chain (lower lower blot 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100360 16877542 129128 9939 5464 IGF1 IGF1 IGF1 7 2.0 Glucose oxidase- and microglial-derived ROS impair the IGF1 Akt pathway in vitro 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100361 16877542 129128 18723 10261 ROS1 ROS ROS 4 0.0 Glucose oxidase- and microglial-derived ROS impair the IGF1 Akt pathway in vitro 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100362 16877542 129128 543 391 AKT1 AKT Akt 8 0.2 Glucose oxidase- and microglial-derived ROS impair the IGF1 Akt pathway in vitro 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100363 16877542 129129 9939 5464 IGF1 IGF1 IGF1-treated 13 1.5 upper blot and total Akt (lower lower blot immunoblots of IGF1-treated SH-SY5Y cells exposed or not exposed to 75 _amp_#x003bc M 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100364 16877542 129129 543 391 AKT1 AKT Akt 8 0.0 ( A Phospho-Akt (upper upper blot and total Akt (lower lower blot immunoblots of IGF1-treated SH-SY5Y cells exposed or 2 JUMiner_v2.2 1 1 akt; 0 0 0 0 0 0 0 0 100365 16877542 129130 20996 11179 SOD1 SOD1 SOD1 4 2.2 ROS reactive oxygen species SOD1 superoxide dismutase 1 IGF1 insulin-like growth factor 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100366 16877542 129130 9939 5464 IGF1 IGF1 IGF1 8 2.0 ROS reactive oxygen species SOD1 superoxide dismutase 1 IGF1 insulin-like growth factor 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100367 16877542 129130 18723 10261 ROS1 ROS ROS 0 0.0 ROS reactive oxygen species SOD1 superoxide dismutase 1 IGF1 insulin-like growth 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100368 16877542 129131 20996 11179 SOD1 ALS ALS 0 2.2 ALS is the most common adult-onset paralytic disease and is characterized 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100369 16877542 129133 20996 11179 SOD1 SOD1 SOD1 18 2.2 dominant mutations in the gene for superoxide dismutase 1 (SOD1) SOD1 cause familial ALS ( 2 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100370 16877542 129133 20996 11179 SOD1 ALS ALS 21 2.2 the gene for superoxide dismutase 1 (SOD1) SOD1 cause familial ALS ( 2 3 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100371 16877542 129134 20996 11179 SOD1 SOD1 SOD1 2 2.2 Overexpression of SOD1 mutants in rodents emulate clinical and pathological hallmarks of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100372 16877542 129134 20996 11179 SOD1 ALS ALS 12 2.2 SOD1 mutants in rodents emulate clinical and pathological hallmarks of ALS through a toxic gain of function ( 4 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100373 16877542 129135 20996 11179 SOD1 SOD1 SOD1 18 2.2 mixture of neuronal and nonneuronal cells expressing wild-type or mutant SOD1 ( 5 investigation of these animals suggested that nonneuronal cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100374 16877542 129136 20996 11179 SOD1 SOD1 SOD1 10 2.2 Corroborating this hypothesis is the demonstration that reduction of mutant SOD1 selectively in microglia extended survival in transgenic SOD1 G37R mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100375 16877542 129136 20996 11179 SOD1 SOD1 SOD1 18 2.2 of mutant SOD1 selectively in microglia extended survival in transgenic SOD1 G37R mice ( 6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100376 16877542 129138 18723 10261 ROS1 ROS ROS 12 0.0 mediators that could promote neurodegeneration are reactive oxygen species (ROS) ROS produced by the enzyme NADPH oxidase complex ( 7 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100377 16877542 129139 18723 10261 ROS1 ROS ROS-generating 2 0.0 Although this ROS-generating multimeric oxidase is indispensable for protecting the host against invading 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 100378 16877542 129141 20996 11179 SOD1 ALS ALS 15 2.2 we undertook the study of NADPH oxidase in both human ALS and one of its genetic models 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100379 16877542 129142 20996 11179 SOD1 ALS ALS 15 2.2 and mouse postmortem tissues indicate that spinal cord microgliosis in ALS is accompanied with an up-regulation of NADPH oxidase 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00136196081569571<>ScoreDetail__5468|IGFALS|0.000485776832861226__11179|SOD1|0.00136196081569571__ 0 0 0 0 0 100380 16877542 129143 18723 10261 ROS1 ROS ROS-generating 29 0.0 provide compelling evidence that supports the concept that this microglial ROS-generating enzymatic complex promotes spinal cord motor neuron degeneration by a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 101191 16883679 129641 9947 5468 IGFALS ALS ALS 3 0.3 Amyotrophic lateral sclerosis (ALS) ALS and asthma are inflammatory diseases 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000996190392783641<>ScoreDetail__5468|IGFALS|0.000133523233042549__11179|SOD1|0.000996190392783641__ 0 0 0 0 0 101192 16883679 129642 9947 5468 IGFALS ALS ALS 0 0.3 ALS is a fatal progressive neurodegenerative disease with inflammation around the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000996190392783641<>ScoreDetail__5468|IGFALS|0.000133523233042549__11179|SOD1|0.000996190392783641__ 0 0 0 0 0 101193 16883679 129645 9947 5468 IGFALS ALS ALS 6 0.3 While there is no cure for ALS asthma is managed according to its symptoms and severity to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000996190392783641<>ScoreDetail__5468|IGFALS|0.000133523233042549__11179|SOD1|0.000996190392783641__ 0 0 0 0 0 101194 16883679 129646 9947 5468 IGFALS ALS ALS 14 0.3 asthma may provide insights into how to clinically deal with ALS the authors examined the etiologies of ALS and asthma and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000996190392783641<>ScoreDetail__5468|IGFALS|0.000133523233042549__11179|SOD1|0.000996190392783641__ 0 0 0 0 0 101195 16883679 129646 9947 5468 IGFALS ALS ALS 21 0.3 clinically deal with ALS the authors examined the etiologies of ALS and asthma and the factors that exacerbate the symptoms 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000996190392783641<>ScoreDetail__5468|IGFALS|0.000133523233042549__11179|SOD1|0.000996190392783641__ 0 0 0 0 0 101425 16892030 129922 20996 11179 SOD1 ALS ALS 0 1.2 ALS life and death in a bad neighborhood 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000320595024365222<>ScoreDetail__5468|IGFALS|0__11179|SOD1|0.000320595024365222__ 0 0 0 0 0 101965 16909005 130926 20996 11179 SOD1 SOD1 SOD1 21 1.7 to the pathogenesis of motor neuron degeneration in the G93A SOD1 transgenic mouse model of amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 101966 16909005 130926 20996 11179 SOD1 ALS ALS 29 1.7 G93A SOD1 transgenic mouse model of amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00156629799558186<>ScoreDetail__5468|IGFALS|0.000360457781382356__11179|SOD1|0.00156629799558186__ 0 0 0 0 0 101967 16909005 130928 9691 5232 HSPA1A HSP70 HSP70 12 1.2 acts potently to increase expression of heat shock proteins including HSP70 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 101968 16909005 130929 20996 11179 SOD1 SOD1 SOD1 8 1.7 We administered it in the diet to G93A SOD1 mice starting at 30 days of age 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 101969 16909005 130930 20996 11179 SOD1 ALS ALS 13 1.7 improved weight loss motor performance and delayed the onset of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00156629799558186<>ScoreDetail__5468|IGFALS|0.000360457781382356__11179|SOD1|0.00156629799558186__ 0 0 0 0 0 101970 16909005 130933 22551 11892 TNF TNF-alpha TNF-alpha 3 2.7 Celastrol treatment reduced TNF-alpha iNOS CD40 and GFAP immunoreactivity in the lumbar spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 101971 16909005 130933 14535 7873 NOS2A iNOS iNOS 4 1.0 Celastrol treatment reduced TNF-alpha iNOS CD40 and GFAP immunoreactivity in the lumbar spinal cord sections 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 101972 16909005 130933 3889 11919 CD40 CD40 CD40 5 0.6 Celastrol treatment reduced TNF-alpha iNOS CD40 and GFAP immunoreactivity in the lumbar spinal cord sections of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 101973 16909005 130933 8254 4235 GFAP GFAP GFAP 7 2.5 Celastrol treatment reduced TNF-alpha iNOS CD40 and GFAP immunoreactivity in the lumbar spinal cord sections of celastrol-treated G93A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 101974 16909005 130934 22551 11892 TNF TNF-alpha TNF-alpha 0 2.7 TNF-alpha immunoreactivity co-localized with SMI-32 (neuronal neuronal marker and GFAP (astrocyte 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 101975 16909005 130934 8254 4235 GFAP GFAP GFAP 8 2.5 TNF-alpha immunoreactivity co-localized with SMI-32 (neuronal neuronal marker and GFAP (astrocyte astrocyte marker 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 101976 16909005 130935 9691 5232 HSPA1A HSP70 HSP70 0 1.2 HSP70 immunoreactivity was increased in lumbar spinal cord neurons of celastrol-treated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 101977 16909005 130936 20996 11179 SOD1 ALS ALS 28 1.7 be a promising therapeutic candidate for the treatment of human ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00156629799558186<>ScoreDetail__5468|IGFALS|0.000360457781382356__11179|SOD1|0.00156629799558186__ 0 0 0 0 0 102045 16909020 130991 9947 5468 IGFALS ALS ALS 21 0.3 of selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) ALS remains unsolved 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000907283918953578<>ScoreDetail__5468|IGFALS|0__11179|SOD1|0.000907283918953578__ 0 0 0 0 0 102046 16909020 130994 9947 5468 IGFALS ALS ALS 7 0.3 This multitude of contributing factors indicates that ALS is a complex disease and also suggests that ALS is 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000907283918953578<>ScoreDetail__5468|IGFALS|0__11179|SOD1|0.000907283918953578__ 0 0 0 0 0 102047 16909020 130994 9947 5468 IGFALS ALS ALS 16 0.3 that ALS is a complex disease and also suggests that ALS is a multifactorial disorder 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000907283918953578<>ScoreDetail__5468|IGFALS|0__11179|SOD1|0.000907283918953578__ 0 0 0 0 0 102048 16909020 130995 9947 5468 IGFALS ALS ALS 11 0.3 is not the newest and most spectacular hypothesis in the ALS field but it is undoubtedly one of the most robust 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000907283918953578<>ScoreDetail__5468|IGFALS|0__11179|SOD1|0.000907283918953578__ 0 0 0 0 0 102049 16909020 130996 9947 5468 IGFALS ALS ALS 15 0.3 riluzole the only drug proven to slow disease progression in ALS is most likely related to its anti-excitotoxic properties 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000907283918953578<>ScoreDetail__5468|IGFALS|0__11179|SOD1|0.000907283918953578__ 0 0 0 0 0 102050 16909020 130997 9947 5468 IGFALS ALS ALS 19 0.3 the arguments in favor of the involvement of excitotoxicity in ALS and of the possible mechanisms leading to motor neuron death 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000907283918953578<>ScoreDetail__5468|IGFALS|0__11179|SOD1|0.000907283918953578__ 0 0 0 0 0 102051 16909020 130998 9947 5468 IGFALS ALS ALS 28 0.3 and could explain the selective vulnerability of motor neurons in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000907283918953578<>ScoreDetail__5468|IGFALS|0__11179|SOD1|0.000907283918953578__ 0 0 0 0 0 102064 16909022 131018 20996 11179 SOD1 ALS ALS 4 1.2 In amyotrophic lateral sclerosis (ALS) ALS degeneration of motor neurons is associated with a chronic and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00121547330976728<>ScoreDetail__5468|IGFALS|0.000714059028879721__11179|SOD1|0.00121547330976728__ 0 0 0 0 0 102065 16909022 131019 20996 11179 SOD1 ALS ALS 10 1.2 There is emerging evidence that the KP is important in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00121547330976728<>ScoreDetail__5468|IGFALS|0.000714059028879721__11179|SOD1|0.00121547330976728__ 0 0 0 0 0 102066 16909022 131020 20996 11179 SOD1 ALS ALS 13 1.2 that QUIN is significantly increased in serum and CSF of ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00121547330976728<>ScoreDetail__5468|IGFALS|0.000714059028879721__11179|SOD1|0.00121547330976728__ 0 0 0 0 0 102067 16909022 131020 11629 6493 LAMC2 CSF CSF 11 0.1 we demonstrated that QUIN is significantly increased in serum and CSF of ALS patients 6 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 102068 16909022 131021 20996 11179 SOD1 ALS ALS 12 1.2 of the factors associated with QUIN toxicity are found in ALS implying that QUIN may play a substantial role in the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00121547330976728<>ScoreDetail__5468|IGFALS|0.000714059028879721__11179|SOD1|0.00121547330976728__ 0 0 0 0 0 102069 16909022 131021 20996 11179 SOD1 ALS ALS 25 1.2 QUIN may play a substantial role in the neuropathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00121547330976728<>ScoreDetail__5468|IGFALS|0.000714059028879721__11179|SOD1|0.00121547330976728__ 0 0 0 0 0 102070 16909022 131022 20996 11179 SOD1 ALS ALS 10 1.2 This review details the potential role the KP has in ALS and advances a testable hypothetical model 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00121547330976728<>ScoreDetail__5468|IGFALS|0.000714059028879721__11179|SOD1|0.00121547330976728__ 0 0 0 0 0 93459 16983747 120732 20996 11179 SOD1 ALS ALS 17 0.0 destruction Parkinson's disease (PD), PD one of dopaminergic neuron depletion ALS a disease of motor neuron death and Alzheimer's a disease 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000898762119587972<>ScoreDetail__5468|IGFALS|0.000187160771102377__11179|SOD1|0.000898762119587972__ 0 0 0 0 0 93460 16983747 120733 926 620 APP amyloid amyloid 23 1.0 inflammation genetic mutations inappropriate protein aggregates (e.g., e.g. Lewy bodies amyloid plaques and biochemical defects leading to apoptosis such as oxidative 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 94199 17008387 122179 14352 7794 NFKB1 NF-kappaB NF-kappaB 10 0.6 dithiocarbamate (PDTC), PDTC an inhibitor of nuclear transcription factor kappa-B NF-kappaB and an antioxidant has beneficial effects in animal models of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94200 17008387 122180 20996 11179 SOD1 ALS ALS 12 2.2 oxidative damage are also hallmarks of amyotrophic lateral sclerosis (ALS), ALS we studied the effect of oral PDTC treatment on G93A-superoxide 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94201 17008387 122180 20996 11179 SOD1 SOD1 SOD1 25 2.5 effect of oral PDTC treatment on G93A-superoxide dismutase 1 (SOD1) SOD1 transgenic (TG) TG rat model of human ALS and observed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94202 17008387 122180 20996 11179 SOD1 ALS ALS 32 2.2 1 (SOD1) SOD1 transgenic (TG) TG rat model of human ALS and observed that PDTC treatment significantly decreases the survival 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94203 17008387 122182 14352 7794 NFKB1 NF-kappaB NF-kappaB 5 0.6 The DNA binding activity of NF-kappaB was not altered in G93A-SOD1 TG rats by PDTC treatment 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94204 17008387 122183 20996 11179 SOD1 SOD1 SOD1 29 2.5 suggesting that increased copper may enhance the neurotoxicity of mutant SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94205 17008387 122187 20996 11179 SOD1 SOD1 SOD1 12 2.5 suggest that PDTC acts as an immunoproteasome inhibitor in mutant SOD1 rats and that immunoproteasome may help the nervous system to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94206 17008387 122188 14352 7794 NFKB1 NF-kappaB NF-kappaB 38 0.6 the treatment of AIDS (Reisinger Reisinger et al. 1990 kappa-B NF-kappaB that regulates the expression of several proinflammatory genes and some 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94207 17008387 122189 20996 11179 SOD1 ALS ALS 3 2.2 Amyotrophic lateral sclerosis (ALS) ALS is a late-onset motor neuron degenerative disease of the spinal 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94208 17008387 122190 20996 11179 SOD1 ALS ALS 3 2.2 The patients with ALS typically become progressively paralyzed and respiratory failure eventually leads to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94209 17008387 122190 20996 11179 SOD1 ALS ALS 31 2.2 et al. 1986 kappaB accompany motor neuron degeneration either in ALS or SOD1 mutant mice (Migheli Migheli et al. 1997 Tortarolo 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94210 17008387 122190 20996 11179 SOD1 SOD1 SOD1 33 2.5 1986 kappaB accompany motor neuron degeneration either in ALS or SOD1 mutant mice (Migheli Migheli et al. 1997 Tortarolo et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94211 17008387 122191 20996 11179 SOD1 ALS ALS 10 2.2 Moreover expression of several proinflammatory mediators is increased both in ALS and SOD1 mutant mice (Alexianu Alexianu et al. 2001 Elliott 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94212 17008387 122191 20996 11179 SOD1 SOD1 SOD1 12 2.5 of several proinflammatory mediators is increased both in ALS and SOD1 mutant mice (Alexianu Alexianu et al. 2001 Elliott 2001 Nguyen 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94213 17008387 122191 20996 11179 SOD1 SOD1 SOD1 36 2.5 al. 2001 and numerous anti-inflammatory compounds prolong survival of TG SOD1 mutant mice (Drachman Drachman et al. 2002 Kriz et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94214 17008387 122192 20996 11179 SOD1 SOD1 SOD1 7 2.5 In addition animal models that express mutant SOD1 exclusively either in motor neurons (Pramatarova Pramatarova et al. 2001 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94215 17008387 122192 20996 11179 SOD1 ALS ALS 51 2.2 interplay between glia and motor neurons is required for the ALS pathogenesis 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94216 17008387 122193 20996 11179 SOD1 ALS ALS 14 2.2 and even apoptosis play major roles in the pathology of ALS we decided to test the effect of PDTC treatment on 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94217 17008387 122195 20996 11179 SOD1 ALS ALS 25 2.2 of immunoproteasome suggesting that immunoproteasome is a beneficial response in ALS to cope with accumulating protein aggregates 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94218 17008387 122197 20996 11179 SOD1 ALS ALS 3 2.2 PDTC Treatment of ALS Rats 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94219 17008387 122224 19573 10691 SDS SDS SDS-polyacrylamide 8 0.0 Cytosolic proteins were separated by 10% or 12% SDS-polyacrylamide gel electrophoresis on Mini-Protean III electrophoresis device (Bio-Rad) Bio-Rad 11 JUMiner_v2.2 1 0 0 2 19440 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:19440|SBDS|0.000221988138576096<>ScoreDetail__10691|SDS|7.57747973024172e-05__19440|SBDS|0.000221988138576096__ 0 0 0 0 0 94220 17008387 122225 17499 9545 PSMB8 LMP7 LMP7 31 2.3 to manufacturer's instructions and immunostained using rabbit polyclonal anti-proteasome 20S LMP7 (dilution dilution 1 1000 Abcam Cambridge UK rabbit polyclonal anti-proteasome 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94221 17008387 122229 20996 11179 SOD1 ALS ALS 70 2.2 _amp_#177 4 days and vehicle-treated (11 11 _amp_#177 3 days ALS rats ( Fig 1 C and D 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94222 17008387 122234 14352 7794 NFKB1 NF-kappaB NF-kappaB 0 0.6 NF-kappaB activation may promote the expression of the genes that mediate 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94223 17008387 122235 14352 7794 NFKB1 NF-kappaB NF-kappaB 15 0.6 cord samples showed no differences in DNA binding activity of NF-kappaB between PDTC and untreated groups ( Fig 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94224 17008387 122236 14352 7794 NFKB1 NF-kappaB NF-kappaB 22 0.6 there was a trend toward increased DNA binding activity of NF-kappaB in G93A-SOD1 TG rats 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94225 17008387 122237 14352 7794 NFKB1 NF-kappaB NF-kappaB 26 0.6 peripheral disease models by inhibiting the activation of transcription factor NF-kappaB serving as a strong antioxidant or by activating Akt-GSK3 beta 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94226 17008387 122237 20996 11179 SOD1 SOD1 SOD1-mediated 63 2.2 beta (Drachman Drachman et al. 2002 beta pathway reduced mutant SOD1-mediated motor neuron cell death in vitro (Koh Koh et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94227 17008387 122238 20017 10940 SLC1A2 GLT-1 GLT-1 12 1.0 that PDTC treatment prevented the reduction of the glutamate transporter GLT-1 a potential therapeutic target verified in numerous animal studies of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94228 17008387 122238 20996 11179 SOD1 ALS ALS 23 2.2 a potential therapeutic target verified in numerous animal studies of ALS (Gurney Gurney et al. 1996 Howland et al. 2002 and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94229 17008387 122239 20996 11179 SOD1 ALS ALS 8 2.2 In agreement with the previous studies on mouse ALS models (Cheroni Cheroni et al. 2005 beta1 beta2 and beta5 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94230 17008387 122239 14317 7762 NEUROD1 BETA2 beta2 15 1.0 on mouse ALS models (Cheroni Cheroni et al. 2005 beta1 beta2 and beta5 have close homologs LMP2 MECL-1 and LMP7 that 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94231 17008387 122239 17500 9546 PSMB9 LMP2 LMP2 21 1.3 et al. 2005 beta1 beta2 and beta5 have close homologs LMP2 MECL-1 and LMP7 that are selectively induced under certain conditions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94232 17008387 122239 17501 9538 PSMB10 MECL1 MECL-1 22 0.3 al. 2005 beta1 beta2 and beta5 have close homologs LMP2 MECL-1 and LMP7 that are selectively induced under certain conditions such 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94233 17008387 122239 17499 9545 PSMB8 LMP7 LMP7 24 2.3 beta1 beta2 and beta5 have close homologs LMP2 MECL-1 and LMP7 that are selectively induced under certain conditions such as the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94234 17008387 122242 20996 11179 SOD1 ALS ALS 43 2.2 which have been reported to be neuroprotective in models of ALS by increasing expression of glutamate transporter GLT-1 (Rothstein Rothstein et 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94235 17008387 122242 20017 10940 SLC1A2 GLT-1 GLT-1 50 1.0 in models of ALS by increasing expression of glutamate transporter GLT-1 (Rothstein Rothstein et al. 2005 beta-lactams because it significantly increases 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94236 17008387 122242 20017 10940 SLC1A2 GLT-1 GLT-1 63 1.0 al. 2005 beta-lactams because it significantly increases the expression of GLT-1 and Cu concentration in the spinal cord We hypothesize that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94237 17008387 122242 20017 10940 SLC1A2 GLT-1 GLT-1 85 1.0 though beta-lactams and PDTC might both be able to modulate GLT-1 and Cu concentration only PDTC but not beta-lactams inhibits immunoproteasome 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94238 17008387 122242 20996 11179 SOD1 ALS ALS 107 2.2 induction of immunoproteasome may be a rather selective characteristic for ALS (models) models compared with models of ischemia trauma and amyloid-accumulating 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94239 17008387 122242 20996 11179 SOD1 ALS ALS 123 2.2 ischemia trauma and amyloid-accumulating diseases inhibition of immunoproteasome alone in ALS models could increase the accumulation of ubiquitinated proteins including ubiquitinated 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94240 17008387 122242 20996 11179 SOD1 SOD1 SOD1 134 2.5 models could increase the accumulation of ubiquitinated proteins including ubiquitinated SOD1 which has been suggested to gain neurotoxic functions such as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94241 17008387 122244 14352 7794 NFKB1 NF-kappaB NF-kappaB 4 0.6 Even though inhibition of NF-kappaB has frequently been associated with tissue and cellular protection inhibition 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94242 17008387 122244 14352 7794 NFKB1 NF-kappaB NF-kappaB 17 0.6 frequently been associated with tissue and cellular protection inhibition of NF-kappaB may also accelerate neurodegeneration because of the survivalsupporting role of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94243 17008387 122244 20996 11179 SOD1 SOD SOD 36 2.2 the survivalsupporting role of some NF-kappaB-regulated genes such as manganese SOD and Bcl-2 (Mattson Mattson and Camandola 2001 kappaB binding activity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94244 17008387 122244 1576 990 BCL2 Bcl-2 Bcl-2 38 1.0 role of some NF-kappaB-regulated genes such as manganese SOD and Bcl-2 (Mattson Mattson and Camandola 2001 kappaB binding activity in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94245 17008387 122244 20996 11179 SOD1 ALS ALS 80 2.2 It is possible that in a long-term disease such as ALS NF-kappaB activity even though being induced is not maintained at 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94246 17008387 122244 14352 7794 NFKB1 NF-kappaB NF-kappaB 81 0.6 is possible that in a long-term disease such as ALS NF-kappaB activity even though being induced is not maintained at so 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94247 17008387 122244 14352 7794 NFKB1 NF-kappaB NF-kappaB 124 0.6 does and thereby does not result in efficient inhibition of NF-kappaB In addition we cannot exclude the possibility that NF-kappaB binding 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94248 17008387 122244 14352 7794 NFKB1 NF-kappaB NF-kappaB 134 0.6 of NF-kappaB In addition we cannot exclude the possibility that NF-kappaB binding to DNA is increased at time points other than 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94249 17008387 122245 14352 7794 NFKB1 NF-kappaB NF-kappaB 12 0.6 experiments do not provide evidence for a central role of NF-kappaB in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94250 17008387 122245 20996 11179 SOD1 ALS ALS 15 2.2 not provide evidence for a central role of NF-kappaB in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94251 17008387 122246 14352 7794 NFKB1 NF-kappaB NF-kappaB 4 0.6 In a previous study NF-kappaB immunoreactivity was found to be increased in astrocytes surrounding degenerating 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94252 17008387 122246 20996 11179 SOD1 ALS ALS 35 2.2 be at least directly involved in neuronal survival in TG ALS models 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94253 17008387 122247 14352 7794 NFKB1 NF-kappaB NF-kappaB 17 0.6 multipotent drug providing protection in various animal models by inhibiting NF-kappaB acting as an antioxidant and activating Akt-GSK3 beta pathway also 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94254 17008387 122247 20017 10940 SLC1A2 GLT-1 GLT-1 30 1.0 as an antioxidant and activating Akt-GSK3 beta pathway also induces GLT-1 a potential drug target in brain diseases 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94255 17008387 122248 20996 11179 SOD1 SOD1 SOD1-containing 38 2.7 in non-neuronal cells and thereby accelerating the formation of toxic SOD1-containing protein aggregates 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94256 17008387 122250 20996 11179 SOD1 ALS ALS 38 2.2 mg kg is not beneficial in a TG model of ALS (L L van den Bosch T Ahtoniemi J Kolstinaho unpublished 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94257 17008387 122251 20996 11179 SOD1 SOD1 SOD1 12 2.5 be important for coping with the toxic consequences of mutant SOD1 in tissues affected by ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94258 17008387 122251 20996 11179 SOD1 ALS ALS 17 2.2 the toxic consequences of mutant SOD1 in tissues affected by ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94259 17008387 122253 20996 11179 SOD1 ALS ALS 3 2.2 PDTC treatment of ALS rats resulted in decreased survival 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94260 17008387 122260 14352 7794 NFKB1 NF-kappaB NF-kappaB 16 0.6 showed no statistically significant differences in DNA binding activity of NF-kappaB between PDTC and untreated groups n = 5 results shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94261 17008387 122264 17499 9545 PSMB8 LMP7 LMP7 4 2.3 The levels of immunoproteasome (LMP7) LMP7 increased along with the disease progression in the spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94262 17008387 122265 17499 9545 PSMB8 LMP7 LMP7 8 2.3 In G93A-SOD1 TG rats the levels of 20S LMP7 protein in the spinal cord was increased 6-fold between 8 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94263 17008387 122268 20017 10940 SLC1A2 GLT-1 GLT-1 8 1.0 PDTC led to decreased immunoproteasome levels and increased GLT-1 levels in TG rats at the end stage whereas PDTC 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94264 17008387 122268 20017 10940 SLC1A2 GLT-1 GLT-1 30 1.0 no effect on the levels of constitutive proteasome immunoproteasome or GLT-1 in WT rats 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94265 17008387 122269 17499 9545 PSMB8 LMP7 LMP7 8 2.3 PDTC treatment completely prevented the induction of 20S LMP7 at the end stage of G93A-SOD1 TG rats (A A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94266 17008387 122270 17499 9545 PSMB8 LMP7 LMP7 9 2.3 A it is noteworthy that in WT animals 20S LMP7 was barely detectable or undetectable in the cytosolic fraction and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94267 17008387 122271 20017 10940 SLC1A2 GLT-1 GLT-1 13 1.0 effect on the levels of astrocyte specific glutamate transporter (GLT-1) GLT-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94268 17008387 122272 20017 10940 SLC1A2 GLT-1 GLT-1 14 1.0 the spinal cords of untreated TG rats the levels of GLT-1 were decreased whereas in PDTC-treated TG rats the levels of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94269 17008387 122272 20017 10940 SLC1A2 GLT-1 GLT-1 25 1.0 were decreased whereas in PDTC-treated TG rats the levels of GLT-1 were at the same levels as in WT rats p 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94270 17008387 122273 17499 9545 PSMB8 LMP7 LMP7 6 2.3 Fig 6 20S X and 20S LMP7 expression in lumbar spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94271 17008387 122275 17499 9545 PSMB8 LMP7 LMP7 2 2.3 B 20S LMP7 an inducible beta-subunit of immunoproteasome was expressed only in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94272 17008387 122279 3901 1693 CD68 CD68 CD68 23 0.3 neurons (stained stained with NeuN and microglia (stained stained with CD68 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94273 17008387 122280 17499 9545 PSMB8 LMP7 LMP7 3 2.3 B immunoproteasome 20S LMP7 was expressed mainly in astrocytes and microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94274 17008387 122286 17499 9545 PSMB8 LMP7 LMP7 23 2.3 cord were used for immunohistochemistry with rabbit polyclonal anti-proteasome 20S LMP7 (dilution dilution 1 500 Abcam or rabbit polyclonal anti-proteasome 20S 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94275 17008387 122286 3901 1693 CD68 CD68 CD68 58 0.3 CA monoclonal NeuN (dilution dilution 1 500 Chemicon or monoclonal CD68 (dilution dilution 1 500 Serotec Oxford UK antibodies 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94276 17008387 122293 20996 11179 SOD1 SOD1 SOD1 1 2.5 Because SOD1 is a major contributor to the cellular Cu concentration copper 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94277 17008387 122304 17499 9545 PSMB8 LMP7 LMP7 22 2.3 spinal cord we used immunoblotting for 20S X and 20S LMP7 markers of constitutive and inducible proteasome respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94278 17008387 122306 17499 9545 PSMB8 LMP7 LMP7 10 2.3 Instead the expression of immunoproteasome measured by immunoblotting for 20S LMP7 an inducible beta subunit was strongly increased in the spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94279 17008387 122307 17499 9545 PSMB8 LMP7 LMP7 3 2.3 The amount of LMP7 protein was increased 6-fold between 8 and 16 weeks of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94280 17008387 122308 17499 9545 PSMB8 LMP7 LMP7 8 2.3 PDTC treatment completely prevented the induction of 20S LMP7 at the end stage of G93A-SOD1 TG rats (1476 1476 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94281 17008387 122309 17499 9545 PSMB8 LMP7 LMP7 8 2.3 It is noteworthy that in WT animals 20S LMP7 was barely detectable or undetectable in the cytosolic fraction ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94282 17008387 122310 20017 10940 SLC1A2 GLT-1 GLT-1 27 1.0 PDTC also increased the levels of astrocyte-specific glutamate transporter (GLT-1) GLT-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94283 17008387 122311 20017 10940 SLC1A2 GLT-1 GLT-1 11 1.0 the spinal cords of untreated TG rats the levels of GLT-1 were decreased whereas in PDTC-treated TG rats the levels of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94284 17008387 122311 20017 10940 SLC1A2 GLT-1 GLT-1 22 1.0 were decreased whereas in PDTC-treated TG rats the levels of GLT-1 were at the same levels as in WT rats ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94285 17008387 122316 17499 9545 PSMB8 LMP7 LMP7 10 2.3 Double-labeling immunohistochemistry with confocal imaging showed that the immunoproteasome 20S LMP7 was expressed in astrocytes and microglia ( Fig 7B whereas 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94286 17008387 122318 20996 11179 SOD1 ALS ALS 4 2.2 ABBREVIATIONS PDTC pyrrolidine dithiocarbamate ALS amyotrophic lateral sclerosis EMSA electrophoretic mobility shift assay NF-kappaB nuclear 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00109824346808189<>ScoreDetail__5468|IGFALS|0.000396780834737039__11179|SOD1|0.00109824346808189__ 0 0 0 0 0 94287 17008387 122318 14352 7794 NFKB1 NF-kappaB NF-kappaB 13 0.6 dithiocarbamate ALS amyotrophic lateral sclerosis EMSA electrophoretic mobility shift assay NF-kappaB nuclear factor kappaB SOD superoxide dismutase WT wild type TG 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 94288 17008387 122318 20996 11179 SOD1 SOD SOD 18 2.2 sclerosis EMSA electrophoretic mobility shift assay NF-kappaB nuclear factor kappaB SOD superoxide dismutase WT wild type TG transgenic GLT glutamate transporter 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81744 17015226 105755 20996 11179 SOD1 ALS ALS 32 4.8 the progressive late-onset motor neuron disease Amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81745 17015226 105758 20996 11179 SOD1 ALS ALS 29 4.8 4_amp_#x2013 6 per 100 000 respectively understates the impact of ALS with the lifetime risk at about 1 in 1000 ( 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81746 17015226 105759 20996 11179 SOD1 ALS ALS 4 4.8 Most incidences (90%) 90% of ALS are sporadic that is without an obvious genetic component 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81747 17015226 105760 20996 11179 SOD1 ALS ALS 13 4.8 in a dominant manner (and and referred to as familial ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81748 17015226 105761 20996 11179 SOD1 ALS ALS 3 4.8 Sporadic and familial ALS produce similar pathological hallmarks including progressive muscle weakness atrophy and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81749 17015226 105765 20996 11179 SOD1 ALS ALS 2 4.8 Genetics of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81750 17015226 105766 20996 11179 SOD1 ALS ALS 3 4.8 Most incidences of ALS are sporadic but 10% of patients have a familial history 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81751 17015226 105767 20996 11179 SOD1 ALS ALS-like 9 4.2 The identified chromosomal loci containing the mutations leading to ALS-like human motor neuron diseases ( Table 1 have been defined 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81752 17015226 105767 20996 11179 SOD1 ALS1 ALS1 22 4.5 motor neuron diseases ( Table 1 have been defined as ALS1 through ALS8 as well as ALS with frontotemporal dementia (ALS-FTD) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81753 17015226 105767 23868 12649 VAPB ALS8 ALS8 24 3.6 diseases ( Table 1 have been defined as ALS1 through ALS8 as well as ALS with frontotemporal dementia (ALS-FTD) ALS-FTD and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81754 17015226 105767 20996 11179 SOD1 ALS ALS 28 4.8 have been defined as ALS1 through ALS8 as well as ALS with frontotemporal dementia (ALS-FTD) ALS-FTD and ALS-FTD coupled with Parkinson's 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81755 17015226 105768 694 483 ANG ANG ANG 6 0.6 Mutations in genes encoding angiogenin ( ANG and VEGF and sequence variants in neurofilament genes have also 1 JUMiner_v2.2 1 0 0 2 483 TotalCon:2<>483|ANG|283|Complete__333|AGT|183|Complete__<>AvaiableGeneRif=2<>BEST:483|ANG|0.00143498588159052<>ScoreDetail__333|AGT|0.000160367500232792__483|ANG|0.00143498588159052__ 0 0 0 0 0 81756 17015226 105768 23910 12680 VEGFA VEGF VEGF 9 4.3 Mutations in genes encoding angiogenin ( ANG and VEGF and sequence variants in neurofilament genes have also been reported 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81757 17015226 105769 20996 11179 SOD1 ALS1 ALS1 16 4.5 that affects motor neurons the nomenclature is misleading since only ALS1 ALS3 ALS6 ALS7 mutations in angiogenin and VEGF and a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81758 17015226 105769 632 444 ALS3 ALS3 ALS3 17 3.0 affects motor neurons the nomenclature is misleading since only ALS1 ALS3 ALS6 ALS7 mutations in angiogenin and VEGF and a small 1 JUMiner_v2.2 1 0 1 0 0 0 0 0 0 0 81759 17015226 105769 632 444 ALS3 ALS6 ALS6 18 3.0 motor neurons the nomenclature is misleading since only ALS1 ALS3 ALS6 ALS7 mutations in angiogenin and VEGF and a small proportion 1 JUMiner_v2.2 1 0 1 0 0 0 0 0 0 0 81760 17015226 105769 23910 12680 VEGFA VEGF VEGF 24 4.3 since only ALS1 ALS3 ALS6 ALS7 mutations in angiogenin and VEGF and a small proportion of incidences of ALS8 represent the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81761 17015226 105769 23868 12649 VAPB ALS8 ALS8 33 3.6 angiogenin and VEGF and a small proportion of incidences of ALS8 represent the classic late-onset neurodegenerative disease with selective killing of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81762 17015226 105770 20996 11179 SOD1 ALS ALS 10 4.8 ALS-FTD and ALS-FTDP are likely appropriately classified as bona fide ALS but patients have additional disease features including dementia and dystonia 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81763 17015226 105771 20996 11179 SOD1 ALS1 ALS1 11 4.5 all of these disease incidences only the genes responsible for ALS1 ALS8 and ALS-FTDP have been identified 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81764 17015226 105771 23868 12649 VAPB ALS8 ALS8 12 3.6 of these disease incidences only the genes responsible for ALS1 ALS8 and ALS-FTDP have been identified 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81765 17015226 105772 20996 11179 SOD1 SOD1 SOD1 2 7.8 ALS1_amp_#x2014 Mutation in SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81766 17015226 105773 20996 11179 SOD1 ALS1 ALS1 8 4.5 The lion's share of work has focused on ALS1 caused by_amp_#xa0 mutations in Cu/Zn Cu Zn superoxide dismutase (SOD1) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81767 17015226 105773 20996 11179 SOD1 SOD1 SOD1 15 7.8 caused by_amp_#xa0 mutations in Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81768 17015226 105774 20996 11179 SOD1 SOD1 SOD1 3 7.8 Mutations in the SOD1 gene are the most common form of inherited ALS accounting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81769 17015226 105774 20996 11179 SOD1 ALS ALS 12 4.8 the SOD1 gene are the most common form of inherited ALS accounting for 20% of all the familial ALS forms and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81770 17015226 105774 20996 11179 SOD1 ALS ALS 20 4.8 of inherited ALS accounting for 20% of all the familial ALS forms and corresponding to 1%_amp_#x2013 2% of all ALS cases 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81771 17015226 105774 20996 11179 SOD1 ALS ALS 28 4.8 familial ALS forms and corresponding to 1%_amp_#x2013 2% of all ALS cases 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81772 17015226 105775 20996 11179 SOD1 SOD1 SOD1 3 7.8 Since the first SOD1 missense mutations were reported in 1993 ( Rosen et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81773 17015226 105777 20996 11179 SOD1 SOD1 SOD1 8 7.8 With the exception of a few instances all SOD1 mutations are dominant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81774 17015226 105778 20996 11179 SOD1 SOD1 SOD1 2 7.8 Sporadic and SOD1 mutant-mediated familial ALS are clinically indistinguishable and affect the same 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81775 17015226 105778 20996 11179 SOD1 ALS ALS 5 4.8 Sporadic and SOD1 mutant-mediated familial ALS are clinically indistinguishable and affect the same neurons but even 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81776 17015226 105779 20996 11179 SOD1 SOD1 SOD1 7 7.8 The alanine-to-valine substitution at position 4 of SOD1 (SOD1 SOD1 A4V is the most prominent mutation in North 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81777 17015226 105779 20996 11179 SOD1 SOD1 SOD1 8 7.8 The alanine-to-valine substitution at position 4 of SOD1 (SOD1 SOD1 A4V is the most prominent mutation in North America responsible 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81778 17015226 105780 20996 11179 SOD1 SOD1 SOD1 10 7.8 Mice and rats expressing mutant forms of human or mouse SOD1 develop progressive motor neuron degeneration ( Bruijn et_amp_#xa0 al. 1997 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81779 17015226 105780 20996 11179 SOD1 ALS ALS 65 4.8 of our knowledge on mechanisms of motor neuron pathology in ALS is from studies using these models (see see below 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81780 17015226 105781 23910 12680 VEGFA VEGF VEGF 4 4.3 Vascular Endothelial Growth Factor (VEGF) VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81781 17015226 105782 23910 12680 VEGFA VEGF VEGF 4 4.3 Vascular endothelial growth factor (VEGF), VEGF an established regulator of developmental hypoxia-induced and tumor-induced angiogenesis gained 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81782 17015226 105782 20996 11179 SOD1 ALS ALS 20 4.8 hypoxia-induced and tumor-induced angiogenesis gained interest as a contributor to ALS when deletion of the hypoxia response element (HRE) HRE in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81783 17015226 105782 23910 12680 VEGFA VEGF VEGF 32 4.3 of the hypoxia response element (HRE) HRE in the murine VEGF promoter resulted in ALS-like disease in mice ( Oosthuyse et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81784 17015226 105782 20996 11179 SOD1 ALS ALS-like 36 4.2 element (HRE) HRE in the murine VEGF promoter resulted in ALS-like disease in mice ( Oosthuyse et_amp_#xa0 al. 2001 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81785 17015226 105783 23910 12680 VEGFA VEGF VEGF 0 4.3 VEGF is widely expressed throughout the central nervous system (CNS) CNS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81786 17015226 105784 20996 11179 SOD1 ALS ALS 2 4.8 Screening of ALS patient DNAs in promoter regions of the VEGF gene including 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81787 17015226 105784 23910 12680 VEGFA VEGF VEGF 10 4.3 Screening of ALS patient DNAs in promoter regions of the VEGF gene including the HRE and regions known to correlate with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81788 17015226 105784 23910 12680 VEGFA VEGF VEGF 23 4.3 the HRE and regions known to correlate with downregulation of VEGF synthesis found no link between HRE variants and disease ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81789 17015226 105785 20996 11179 SOD1 ALS ALS 15 4.8 of the promoter however showed an increased risk of developing ALS in a Belgian Swedish and a British/Birmingham British Birmingham population 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81790 17015226 105786 694 483 ANG ANG ANG 2 0.6 Angiogenin ( ANG 1 JUMiner_v2.2 1 0 0 2 483 TotalCon:2<>483|ANG|283|Complete__333|AGT|183|Complete__<>AvaiableGeneRif=2<>BEST:483|ANG|0.00143498588159052<>ScoreDetail__333|AGT|0.000160367500232792__483|ANG|0.00143498588159052__ 0 0 0 0 0 81791 17015226 105787 694 483 ANG ANG ANG 2 0.6 Mutations in ANG have also been linked to ALS emphasizing a potential link 1 JUMiner_v2.2 1 0 0 2 483 TotalCon:2<>483|ANG|283|Complete__333|AGT|183|Complete__<>AvaiableGeneRif=2<>BEST:483|ANG|0.00143498588159052<>ScoreDetail__333|AGT|0.000160367500232792__483|ANG|0.00143498588159052__ 0 0 0 0 0 81792 17015226 105787 20996 11179 SOD1 ALS ALS 8 4.8 Mutations in ANG have also been linked to ALS emphasizing a potential link between altered angiogenesis and motor neuron 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81793 17015226 105788 20996 11179 SOD1 ALS ALS 10 4.8 Seven missense mutations were identified in 15 patients with familial ALS and 11 apparently sporadic ALS patients ( Greenway et_amp_#xa0 al. 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81794 17015226 105788 20996 11179 SOD1 ALS ALS 15 4.8 in 15 patients with familial ALS and 11 apparently sporadic ALS patients ( Greenway et_amp_#xa0 al. 2006 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81795 17015226 105789 20996 11179 SOD1 ALS ALS-linked 26 4.2 English Swedish and North American populations and therefore suggest that ALS-linked ANG mutations are rare 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81796 17015226 105789 694 483 ANG ANG ANG 27 0.6 Swedish and North American populations and therefore suggest that ALS-linked ANG mutations are rare 1 JUMiner_v2.2 1 0 0 2 483 TotalCon:2<>483|ANG|283|Complete__333|AGT|183|Complete__<>AvaiableGeneRif=2<>BEST:483|ANG|0.00143498588159052<>ScoreDetail__333|AGT|0.000160367500232792__483|ANG|0.00143498588159052__ 0 0 0 0 0 81797 17015226 105792 20996 11179 SOD1 ALS ALS 8 4.8 Interestingly the majority of the mutations found in ALS patients are located within the catalytic core and one of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81798 17015226 105793 23910 12680 VEGFA VEGF VEGF 8 4.3 Whether angiogenin is endowed with neurotrophic properties like VEGF in addition to its angiogenic activity is not yet established 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81799 17015226 105794 23868 12649 VAPB VAPB VAPB 3 4.2 ALS8_amp_#x2014 VAMP-Associated Protein B (VAPB) VAPB 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81800 17015226 105795 20996 11179 SOD1 ALS ALS 29 4.8 disease course with most instances of disease representing an atypical ALS that is accompanied by an unusual tremor ( Nishimura et_amp_#xa0 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81801 17015226 105796 20996 11179 SOD1 ALS ALS 25 4.8 and a small proportion of patients develop symptoms of classic ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81802 17015226 105797 23868 12649 VAPB VAPB VAPB 21 4.2 gene encoding v esicle-a ssociated membrane p rotein B ( VAPB also known as synaptobrevin-associated protein B VAPB has been implicated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81803 17015226 105797 23868 12649 VAPB VAPB VAPB 29 4.2 rotein B ( VAPB also known as synaptobrevin-associated protein B VAPB has been implicated in endoplasmic reticulum to Golgi transport albeit 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81804 17015226 105798 23868 12649 VAPB VAPB VAPB 19 4.2 position 56 affects the functional properties of the ubiquitously expressed VAPB 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81805 17015226 105800 20996 11179 SOD1 ALS ALS 14 4.8 three neurofilament subunits have long been suspected as causative for ALS because of their link with motor neuron pathology in mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81806 17015226 105801 20996 11179 SOD1 ALS ALS 21 4.8 accumulations are a pathological hallmark of both familial and sporadic ALS ( Hirano 1991 Hirano et_amp_#xa0 al. 1984a and Hirano et_amp_#xa0 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81807 17015226 105801 20996 11179 SOD1 ALS ALS 39 4.8 and Hirano et_amp_#xa0 al. 1984b and are also seen in ALS mice expressing mutant SOD1 ( Bruijn et_amp_#xa0 al. 1997 and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81808 17015226 105801 20996 11179 SOD1 SOD1 SOD1 43 7.8 1984b and are also seen in ALS mice expressing mutant SOD1 ( Bruijn et_amp_#xa0 al. 1997 and Dal Canto and Gurney 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81809 17015226 105802 14280 7737 NEFH NFH NF-H 8 0.9 In addition mice with increased levels of wild-type NF-H or NF-L subunits develop age-dependent motor neuron pathology ( Cote 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81810 17015226 105802 14282 7739 NEFL NF-L NF-L 10 2.4 In addition mice with increased levels of wild-type NF-H or NF-L subunits develop age-dependent motor neuron pathology ( Cote et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81811 17015226 105802 14282 7739 NEFL NF-L NF-L 33 2.4 et_amp_#xa0 al. 1993 while expression of a point mutation in NF-L at levels corresponding to that expected for dominantly inherited disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81812 17015226 105803 20996 11179 SOD1 ALS ALS 24 4.8 failed to yield conclusive linkage to either sporadic or familial ALS patients ( Garcia et_amp_#xa0 al. 2006 although dominant point mutations 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81813 17015226 105803 14282 7739 NEFL NF-L NF-L 36 2.4 ( Garcia et_amp_#xa0 al. 2006 although dominant point mutations in NF-L have been linked to a milder motor neuron disease Charcot-Marie-Tooth 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81814 17015226 105804 14280 7737 NEFH NFH NF-H 21 0.9 or 45 KSP repeats in the tail domain of the NF-H subunit have been reported in 1% of sporadic ALS patients 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81815 17015226 105804 20996 11179 SOD1 ALS ALS 30 4.8 the NF-H subunit have been reported in 1% of sporadic ALS patients ( Al-Chalabi et_amp_#xa0 al. 1999 Figlewicz et_amp_#xa0 al. 1994 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81816 17015226 105805 20996 11179 SOD1 ALS ALS 12 4.8 is likely that these neurofilament variants are risk factors for ALS and/or and or a primary event with low penetrance 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81817 17015226 105806 20996 11179 SOD1 ALS ALS 7 4.8 A final potential contribution of neurofilaments to ALS comes from errors in the expression of an additional intermediate 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81818 17015226 105807 20996 11179 SOD1 ALS ALS 10 4.8 An assembly-disrupting frameshift mutation has been reported in one sporadic ALS case ( Gros-Louis et_amp_#xa0 al. 2004 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81819 17015226 105808 20996 11179 SOD1 ALS ALS-causing 53 4.2 has no affect on disease course in mice having an ALS-causing SOD1 mutation ( Lariviere et_amp_#xa0 al. 2003 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81820 17015226 105808 20996 11179 SOD1 SOD1 SOD1 54 7.8 no affect on disease course in mice having an ALS-causing SOD1 mutation ( Lariviere et_amp_#xa0 al. 2003 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81821 17015226 105809 20996 11179 SOD1 SOD1 SOD1 7 7.8 Motor Neuron Death from Toxicity of Mutant SOD1 Not Loss of Dismutase Activity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81822 17015226 105810 20996 11179 SOD1 SOD1 SOD1 0 7.8 SOD1 is an abundant ubiquitously expressed cytosolic enzyme 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81823 17015226 105811 20996 11179 SOD1 SOD1 SOD1 5 7.8 Since the known activity of SOD1 is to dismutate (or or convert superoxide a natural byproduct 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81824 17015226 105812 20996 11179 SOD1 SOD1 hSOD1 5 4.2 However animals expressing dismutase active (hSOD1 hSOD1 G37R Wong et_amp_#xa0 al. 1995 and hSOD1 G93A Gurney et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81825 17015226 105812 20996 11179 SOD1 SOD1 hSOD1 13 4.2 dismutase active (hSOD1 hSOD1 G37R Wong et_amp_#xa0 al. 1995 and hSOD1 G93A Gurney et_amp_#xa0 al. 1994 and Howland et_amp_#xa0 al. 2002 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81826 17015226 105812 20996 11179 SOD1 SOD1 hSOD1 28 4.2 and Howland et_amp_#xa0 al. 2002 as well as inactive (hSOD1 hSOD1 G85R Bruijn et_amp_#xa0 al. 1997 mSOD1 G86R Ripps et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81827 17015226 105812 20996 11179 SOD1 SOD1 mSOD1 35 4.2 well as inactive (hSOD1 hSOD1 G85R Bruijn et_amp_#xa0 al. 1997 mSOD1 G86R Ripps et_amp_#xa0 al. 1995 hSOD1 G127X Jonsson et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81828 17015226 105812 20996 11179 SOD1 SOD1 hSOD1 42 4.2 Bruijn et_amp_#xa0 al. 1997 mSOD1 G86R Ripps et_amp_#xa0 al. 1995 hSOD1 G127X Jonsson et_amp_#xa0 al. 2004 hSOD1 Quad Wang et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81829 17015226 105812 20996 11179 SOD1 SOD1 hSOD1 49 4.2 Ripps et_amp_#xa0 al. 1995 hSOD1 G127X Jonsson et_amp_#xa0 al. 2004 hSOD1 Quad Wang et_amp_#xa0 al. 2003 hSOD1 H46R Nagai et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81830 17015226 105812 20996 11179 SOD1 SOD1 hSOD1 56 4.2 Jonsson et_amp_#xa0 al. 2004 hSOD1 Quad Wang et_amp_#xa0 al. 2003 hSOD1 H46R Nagai et_amp_#xa0 al. 2001 forms of the enzyme develop 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81831 17015226 105813 20996 11179 SOD1 SOD1 SOD1 1 7.8 Furthermore SOD1 gene deletion in mice does not lead to motor neuron 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81832 17015226 105814 20996 11179 SOD1 SOD1 SOD1 7 7.8 In addition deletion of the endogenous mouse SOD1 in mice expressing dismutase inactive hSOD1 G85R does not affect 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81833 17015226 105814 20996 11179 SOD1 SOD1 hSOD1 13 4.2 of the endogenous mouse SOD1 in mice expressing dismutase inactive hSOD1 G85R does not affect disease course ( Bruijn et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81834 17015226 105815 20996 11179 SOD1 SOD1 SOD1 7 7.8 Mice expressing high levels of wild-type human SOD1 (hSOD1 hSOD1 WT transgene are healthy ( Gurney et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81835 17015226 105815 20996 11179 SOD1 SOD1 hSOD1 8 4.2 Mice expressing high levels of wild-type human SOD1 (hSOD1 hSOD1 WT transgene are healthy ( Gurney et_amp_#xa0 al. 1994 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81836 17015226 105816 20996 11179 SOD1 SOD1 hSOD1 2 4.2 Indeed increased hSOD1 WT accompanied by chronic elevation of dismutase activity has either 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81837 17015226 105818 20996 11179 SOD1 SOD1 SOD1 0 7.8 SOD1 activity is dependent on a catalytic copper 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81838 17015226 105819 20996 11179 SOD1 SOD1 SOD1 13 7.8 is highly reactive and toxic it must be loaded onto SOD1 by a copper chaperone for SOD1 (CCS; CCS Corson et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81839 17015226 105819 20996 11179 SOD1 SOD1 SOD1 19 7.8 must be loaded onto SOD1 by a copper chaperone for SOD1 (CCS; CCS Corson et_amp_#xa0 al. 1998 and Wong et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81840 17015226 105819 3838 1613 CCS CCS CCS 20 1.7 loaded onto SOD1 by a copper chaperone for SOD1 (CCS; CCS Corson et_amp_#xa0 al. 1998 and Wong et_amp_#xa0 al. 2000b and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81841 17015226 105819 3838 1613 CCS CCS CCS 44 1.7 by a conserved disulfide bond whose formation is catalyzed by CCS ( Furukawa et_amp_#xa0 al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81842 17015226 105820 3838 1613 CCS CCS CCS 1 1.7 Since CCS is abundantly expressed in motor neurons ( Rothstein et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81843 17015226 105820 3838 1613 CCS CCS CCS 17 1.7 neurons ( Rothstein et_amp_#xa0 al. 1999 and motor neurons of CCS -deleted mice have an increased sensitivity to axotomy-induced death ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81844 17015226 105820 20996 11179 SOD1 SOD1 SOD1 41 7.8 2002 it was postulated that inefficient incorporation of copper into SOD1 and/or and or a decreased shielding of copper (due due 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81845 17015226 105820 20996 11179 SOD1 SOD1 SOD1 52 7.8 a decreased shielding of copper (due due to changes in SOD1 structure as a result of mutation could provide an opportunity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81846 17015226 105821 20996 11179 SOD1 SOD1 SOD1 14 7.8 using mice in which the incorporation of copper into mutant SOD1 was significantly reduced by disruption of the CCS gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81847 17015226 105821 3838 1613 CCS CCS CCS 22 1.7 into mutant SOD1 was significantly reduced by disruption of the CCS gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81848 17015226 105823 20996 11179 SOD1 SOD1 hSOD1 11 4.2 in which all four copper-binding histidines have been eliminated (hSOD1 hSOD1 Quad resulting in dismutase inactive SOD1 still develop typical ALS-like 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81849 17015226 105823 20996 11179 SOD1 SOD1 SOD1 18 7.8 have been eliminated (hSOD1 hSOD1 Quad resulting in dismutase inactive SOD1 still develop typical ALS-like motor neuron disease ( Wang et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81850 17015226 105823 20996 11179 SOD1 ALS ALS-like 22 4.2 hSOD1 Quad resulting in dismutase inactive SOD1 still develop typical ALS-like motor neuron disease ( Wang et_amp_#xa0 al. 2003 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81851 17015226 105824 20996 11179 SOD1 SOD1 SOD1 16 7.8 toxic property (or or properties acquired as a result of SOD1 mutation (1) 1 are independent of dismutase and CCS activities 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81852 17015226 105824 3838 1613 CCS CCS CCS 24 1.7 of SOD1 mutation (1) 1 are independent of dismutase and CCS activities and (2) 2 can be generated without catalysis by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81853 17015226 105825 20996 11179 SOD1 SOD1 SOD1 1 7.8 Misfolded SOD1 as a Common Feature of ALS-Causing Mutations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81854 17015226 105825 20996 11179 SOD1 ALS ALS-Causing 7 4.2 Misfolded SOD1 as a Common Feature of ALS-Causing Mutations 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81855 17015226 105826 20996 11179 SOD1 ALS ALS 17 4.8 different neurodegenerative disorders including Alzheimer's Parkinson's and Huntington's diseases and ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81856 17015226 105827 20996 11179 SOD1 ALS ALS 10 4.8 Cytoplasmic protein aggregates are observed in both sporadic and familial ALS cases as well as in mutant SOD1 transgenic mice ( 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81857 17015226 105827 20996 11179 SOD1 SOD1 SOD1 17 7.8 sporadic and familial ALS cases as well as in mutant SOD1 transgenic mice ( Bruijn et_amp_#xa0 al. 1997 Bruijn et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81858 17015226 105830 20996 11179 SOD1 SOD1 SOD1 14 7.8 used to define accumulations of detergent-insoluble forms of proteins including SOD1 that are detected by immunoblotting of filter-trappable material as well 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81859 17015226 105830 20996 11179 SOD1 SOD1 SOD1- 27 4.5 detected by immunoblotting of filter-trappable material as well as small SOD1- or ubiquitin-positive fibrillar inclusions in spinal cord sections ( Deng 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81860 17015226 105831 20996 11179 SOD1 SOD1 SOD1 10 7.8 Detergent-insoluble species are detectable only in affected tissues of mutant SOD1 mice and are most prominent at symptomatic stages ( Furukawa 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81861 17015226 105832 20996 11179 SOD1 SOD1 SOD1 9 7.8 A propensity to form aggregates following synthesis of mutant SOD1 in primary cells is selective to motor neurons as aggregates 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81862 17015226 105833 20996 11179 SOD1 SOD1 SOD1 4 7.8 The most misfolded unstable SOD1 mutants (with with the shortest in vivo half-lives are most 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81863 17015226 105834 20996 11179 SOD1 SOD1 hSOD1 14 4.2 unexplained aspect of disease is that the very unstable mutant hSOD1 A4V ( Sato et_amp_#xa0 al. 2005 which provokes a very 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81864 17015226 105834 20996 11179 SOD1 ALS ALS-like 34 4.2 very aggressive disease course in humans neither induces aggregates nor ALS-like disease in mice except in the context of high levels 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81865 17015226 105834 20996 11179 SOD1 SOD1 hSOD1 46 4.2 in mice except in the context of high levels of hSOD1 WT ( Deng et_amp_#xa0 al. 2006 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81866 17015226 105835 20996 11179 SOD1 SOD1 hSOD1 2 4.2 Similarly increased hSOD1 WT accelerated disease from a second unstable mutant hSOD1 L126Z 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81867 17015226 105835 20996 11179 SOD1 SOD1 hSOD1 11 4.2 increased hSOD1 WT accelerated disease from a second unstable mutant hSOD1 L126Z 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81868 17015226 105836 20996 11179 SOD1 SOD1 hSOD1 14 4.2 be mediated by_amp_#xa0 stabilization of the mutant via heterodimerization with_amp_#xa0 hSOD1 WT protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81869 17015226 105837 20996 11179 SOD1 SOD1 hSOD1 6 4.2 Indeed in both cases increased levels_amp_#xa0 of hSOD1 WT generated detergent-insoluble forms of SOD1 that were not seen 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81870 17015226 105837 20996 11179 SOD1 SOD1 SOD1 12 7.8 cases increased levels_amp_#xa0 of hSOD1 WT generated detergent-insoluble forms of SOD1 that were not seen in spinal cord extracts of hSOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81871 17015226 105837 20996 11179 SOD1 SOD1 hSOD1 22 4.2 SOD1 that were not seen in spinal cord extracts of hSOD1 A4V or hSOD1 L126Z mice alone 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81872 17015226 105837 20996 11179 SOD1 SOD1 hSOD1 25 4.2 not seen in spinal cord extracts of hSOD1 A4V or hSOD1 L126Z mice alone 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81873 17015226 105838 20996 11179 SOD1 SOD1 SOD1 1 7.8 Are SOD1 Aggregates Toxic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81874 17015226 105842 20996 11179 SOD1 ALS ALS 3 4.8 Aggregates found in ALS patients as well as mouse models contain ubiquitin ( Ince 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81875 17015226 105844 20996 11179 SOD1 SOD1 SOD1 4 7.8 Indeed the degradation of SOD1 itself and aggregates of SOD1 is proteasome mediated ( Basso 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81876 17015226 105844 20996 11179 SOD1 SOD1 SOD1 9 7.8 Indeed the degradation of SOD1 itself and aggregates of SOD1 is proteasome mediated ( Basso et_amp_#xa0 al. 2006 Niwa et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81877 17015226 105847 20996 11179 SOD1 SOD1 hSOD1 1 4.2 In hSOD1 G93A mice which accumulate mutant protein to high levels proteasome 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81878 17015226 105849 9691 5232 HSPA1A HSP HSPs 13 0.6 examined the protein folding chaperone machinery the heat-shock proteins (HSPs), HSPs in the context of disease 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81879 17015226 105850 20996 11179 SOD1 ALS ALS 6 4.8 In spinal cord extracts of presymptomatic ALS mice an overall decrease of chaperone activity has been reported 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81880 17015226 105850 20996 11179 SOD1 SOD1 SOD1 25 7.8 been reported which persists throughout disease course and multiple recombinant SOD1 mutants inhibit chaperone function in vitro ( Bruening et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81881 17015226 105851 9691 5232 HSPA1A HSP HSPs 2 0.6 Paradoxically some HSPs such as _amp_#x3b1 B-crystallin and Hsp27 are elevated in the 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81882 17015226 105851 9707 5246 HSPB1 HSP27 Hsp27 7 3.4 Paradoxically some HSPs such as _amp_#x3b1 B-crystallin and Hsp27 are elevated in the spinal cords of hSOD1 G37R and 2 JUMiner_v2.2 1 0 0 2 5246 TotalCon:2<>5246|HSPB1|3315|Complete__5247|HSPB2|3316|Complete__<>AvaiableGeneRif=2<>BEST:5246|HSPB1|0.000499946228238831<>ScoreDetail__5246|HSPB1|0.000499946228238831__5247|HSPB2|0.000423484630829349__ 0 0 0 0 0 81883 17015226 105851 20996 11179 SOD1 SOD1 hSOD1 15 4.2 B-crystallin and Hsp27 are elevated in the spinal cords of hSOD1 G37R and hSOD1 G93A mice but Hsp27 is predominantly present 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81884 17015226 105851 20996 11179 SOD1 SOD1 hSOD1 18 4.2 are elevated in the spinal cords of hSOD1 G37R and hSOD1 G93A mice but Hsp27 is predominantly present in glial cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81885 17015226 105851 9707 5246 HSPB1 HSP27 Hsp27 22 3.4 spinal cords of hSOD1 G37R and hSOD1 G93A mice but Hsp27 is predominantly present in glial cells in late disease stages 2 JUMiner_v2.2 1 0 0 2 5246 TotalCon:2<>5246|HSPB1|3315|Complete__5247|HSPB2|3316|Complete__<>AvaiableGeneRif=2<>BEST:5246|HSPB1|0.000499946228238831<>ScoreDetail__5246|HSPB1|0.000499946228238831__5247|HSPB2|0.000423484630829349__ 0 0 0 0 0 81886 17015226 105852 9691 5232 HSPA1A HSP70 Hsp70 0 0.6 Hsp70 Hsp40 and Hsp90 are also elevated but only in the 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81887 17015226 105852 5968 5270 DNAJB1 Hsp40 Hsp40 1 1.0 Hsp70 Hsp40 and Hsp90 are also elevated but only in the spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81888 17015226 105852 9676 5253 HSP90AA1 Hsp90 Hsp90 3 1.6 Hsp70 Hsp40 and Hsp90 are also elevated but only in the spinal cords of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81889 17015226 105852 20996 11179 SOD1 SOD1 hSOD1 14 4.2 are also elevated but only in the spinal cords of hSOD1 G85R mice ( Liu et_amp_#xa0 al. 2005 Vleminckx et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81890 17015226 105853 20996 11179 SOD1 ALS ALS 29 4.8 al. 2003 which may contribute to their selective vulnerability in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81891 17015226 105854 20996 11179 SOD1 SOD1 SOD1-mediated 1 4.5 Mutant SOD1-mediated depletion of HSPs is a plausible possibility given that Hsp70 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81892 17015226 105854 9691 5232 HSPA1A HSP HSPs 4 0.6 Mutant SOD1-mediated depletion of HSPs is a plausible possibility given that Hsp70 and Hsp25 preferentially 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81893 17015226 105854 9691 5232 HSPA1A HSP70 Hsp70 11 0.6 SOD1-mediated depletion of HSPs is a plausible possibility given that Hsp70 and Hsp25 preferentially bind mutant SOD1 ( Okado-Matsumoto and Fridovich 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81894 17015226 105854 9707 5246 HSPB1 Hsp25 Hsp25 13 3.1 of HSPs is a plausible possibility given that Hsp70 and Hsp25 preferentially bind mutant SOD1 ( Okado-Matsumoto and Fridovich 2002 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81895 17015226 105854 20996 11179 SOD1 SOD1 SOD1 17 7.8 plausible possibility given that Hsp70 and Hsp25 preferentially bind mutant SOD1 ( Okado-Matsumoto and Fridovich 2002 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81896 17015226 105855 9691 5232 HSPA1A HSP HSPs 4 0.6 Expression of several different HSPs (Hsp70, Hsp70 Hsp40 Hsp27 in cultured cells and primary motor 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81897 17015226 105855 9691 5232 HSPA1A HSP70 Hsp70 5 0.6 Expression of several different HSPs (Hsp70, Hsp70 Hsp40 Hsp27 in cultured cells and primary motor neurons decreases 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81898 17015226 105855 5968 5270 DNAJB1 Hsp40 Hsp40 6 1.0 Expression of several different HSPs (Hsp70, Hsp70 Hsp40 Hsp27 in cultured cells and primary motor neurons decreases aggregate 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81899 17015226 105855 9707 5246 HSPB1 HSP27 Hsp27 7 3.4 Expression of several different HSPs (Hsp70, Hsp70 Hsp40 Hsp27 in cultured cells and primary motor neurons decreases aggregate content 2 JUMiner_v2.2 1 0 0 2 5246 TotalCon:2<>5246|HSPB1|3315|Complete__5247|HSPB2|3316|Complete__<>AvaiableGeneRif=2<>BEST:5246|HSPB1|0.000499946228238831<>ScoreDetail__5246|HSPB1|0.000499946228238831__5247|HSPB2|0.000423484630829349__ 0 0 0 0 0 81900 17015226 105856 9691 5232 HSPA1A HSP70 Hsp70 10 0.6 Unfortunately applying this strategy in vivo by increased expression of Hsp70 in four different mutant SOD1 mouse lines did not ameliorate 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81901 17015226 105856 20996 11179 SOD1 SOD1 SOD1 15 7.8 vivo by increased expression of Hsp70 in four different mutant SOD1 mouse lines did not ameliorate disease or pathology ( Liu 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81902 17015226 105857 20996 11179 SOD1 SOD1 hSOD1 14 4.2 stress response extended life span in a small cohort of hSOD1 G93A mice after treatment with arimoclomol a drug which induces 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81903 17015226 105857 9691 5232 HSPA1A HSP HSP 30 0.6 arimoclomol a drug which induces the phosphorylation-mediated activation of the HSP inducing factor HSF-1 thereby leading to increased levels of Hsp70 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81904 17015226 105857 9665 5224 HSF1 HSF1 HSF-1 33 0.9 which induces the phosphorylation-mediated activation of the HSP inducing factor HSF-1 thereby leading to increased levels of Hsp70 and Hsp90 in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81905 17015226 105857 9691 5232 HSPA1A HSP70 Hsp70 40 0.6 HSP inducing factor HSF-1 thereby leading to increased levels of Hsp70 and Hsp90 in spinal cords ( Kieran et_amp_#xa0 al. 2004 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81906 17015226 105857 9676 5253 HSP90AA1 Hsp90 Hsp90 42 1.6 factor HSF-1 thereby leading to increased levels of Hsp70 and Hsp90 in spinal cords ( Kieran et_amp_#xa0 al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81907 17015226 105858 9707 5246 HSPB1 HSP27 Hsp27 7 3.4 Interestingly missense mutations in the gene encoding Hsp27 have been identified in a number of families with distal 2 JUMiner_v2.2 1 0 0 2 5246 TotalCon:2<>5246|HSPB1|3315|Complete__5247|HSPB2|3316|Complete__<>AvaiableGeneRif=2<>BEST:5246|HSPB1|0.000499946228238831<>ScoreDetail__5246|HSPB1|0.000499946228238831__5247|HSPB2|0.000423484630829349__ 0 0 0 0 0 81908 17015226 105861 20996 11179 SOD1 ALS ALS 10 4.8 Mitochondria were implicated as a possible target for toxicity in ALS by histopathological observations of vacuolated and dilated mitochondria with disorganized 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81909 17015226 105861 20996 11179 SOD1 ALS ALS 35 4.8 motor neurons (and and muscle of both sporadic and familial ALS patients ( Afifi et_amp_#xa0 al. 1966 Hirano et_amp_#xa0 al. 1984a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81910 17015226 105862 18111 5724 RBPJ SUH Suh 30 0.6 respiration and increased levels of uncoupling proteins ( Chung and Suh 2002 Dupuis et_amp_#xa0 al. 2003 Echaniz-Laguna et_amp_#xa0 al. 2002 Vielhaber 2 JUMiner_v2.2 1 2 UserEdit 0 2 5724 TotalCon:2<>5724|RBPJ|3516|Complete__13761|RBPJL|11317|Complete__<>AvaiableGeneRif=2<>BEST:5724|RBPJ|0.00027587698614083<>ScoreDetail__5724|RBPJ|0.00027587698614083__13761|RBPJL|0.000145008887641501__ 1 1 0 0 0 81911 17015226 105864 20996 11179 SOD1 SOD1 hSOD1 22 4.2 that develop disease from accumulation of dismutase active mutants (hSOD1 hSOD1 G37R Wong et_amp_#xa0 al. 1995 and hSOD1 G93A mice Dal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81912 17015226 105864 20996 11179 SOD1 SOD1 hSOD1 30 4.2 active mutants (hSOD1 hSOD1 G37R Wong et_amp_#xa0 al. 1995 and hSOD1 G93A mice Dal Canto and Gurney 1994 Higgins et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81913 17015226 105866 20996 11179 SOD1 SOD1 hSOD1 21 4.2 been described in mice with very high accumulated levels of hSOD1 WT protein ( Jaarsma et_amp_#xa0 al. 2000 and Jaarsma et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81914 17015226 105868 20996 11179 SOD1 SOD1 SOD1 6 7.8 A proportion of the predominantly cytosolic SOD1 localizes to mitochondria in certain contexts 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81915 17015226 105869 20996 11179 SOD1 SOD1 SOD1 8 7.8 In both rodent models and patient samples mutant SOD1 is present in fractions enriched for mitochondria derived from affected 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81916 17015226 105870 20996 11179 SOD1 SOD1 SOD1 3 7.8 Mitochondrial localization of SOD1 has been confirmed by electron microscopy in both isolated mitochondria 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81917 17015226 105871 20996 11179 SOD1 SOD1 SOD1 0 7.8 SOD1 mutants that cause disease at the lowest accumulated levels (hSOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81918 17015226 105871 20996 11179 SOD1 SOD1 hSOD1 10 4.2 mutants that cause disease at the lowest accumulated levels (hSOD1 hSOD1 G85R and hSOD1 G127X all dismutase inactive have the highest 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81919 17015226 105871 20996 11179 SOD1 SOD1 hSOD1 13 4.2 disease at the lowest accumulated levels (hSOD1 hSOD1 G85R and hSOD1 G127X all dismutase inactive have the highest relative proportions that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81920 17015226 105872 20996 11179 SOD1 SOD1 SOD1 10 7.8 disagreement in defining the submitochondrial compartment(s) compartment s with which SOD1 is localized (or or potentially aggregated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81921 17015226 105873 20996 11179 SOD1 SOD1 SOD1 1 7.8 Mutant SOD1 has been reported in both the intermembrane space and the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81922 17015226 105874 20996 11179 SOD1 SOD1 SOD1 12 7.8 apparent contradictions remain to be resolved all reports agree that SOD1 mutant proteins of divergent biochemical characteristics localize to mitochondria consistent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81923 17015226 105876 20996 11179 SOD1 SOD1 SOD1 11 7.8 there some intrinsic feature of spinal cord mitochondria which permits SOD1 association and/or and or increases mitochondrial vulnerability to mutant SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81924 17015226 105876 20996 11179 SOD1 SOD1 SOD1 19 7.8 SOD1 association and/or and or increases mitochondrial vulnerability to mutant SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81925 17015226 105879 20996 11179 SOD1 SOD1 SOD1 6 7.8 Of relevance here the endogenous wild-type SOD1 protein is largely excluded from spinal cord mitochondria but all 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81926 17015226 105879 20996 11179 SOD1 SOD1 SOD1 18 7.8 is largely excluded from spinal cord mitochondria but all human SOD1 mutants examined to date are mitochondrially associated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81927 17015226 105880 20996 11179 SOD1 SOD1 SOD1 25 7.8 Liu et_amp_#xa0 al. 2004 despite a proportion of endogenous mouse SOD1 localized to the intermembrane space of those mitochondria ( Liu 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81928 17015226 105882 20996 11179 SOD1 SOD1 SOD1 2 7.8 How mutant SOD1 affects mitochondrial function is not yet clear but differences in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81929 17015226 105885 1016 13209 ARHGEF5 TIM TIM 21 0.3 translocators of the outer and inner membrane (TOM TOM and TIM respectively 1 JUMiner_v2.2 1 0 0 2 11813 TotalCon:2<>13209|ARHGEF5|7984|Complete__11813|TIMELESS|8914|Complete__<>AvaiableGeneRif=2<>BEST:11813|TIMELESS|0.000217395547496889<>ScoreDetail__13209|ARHGEF5|0.000187108242118065__11813|TIMELESS|0.000217395547496889__ 0 0 0 0 0 81930 17015226 105885 17370 15860 PRPF6 TOM TOM 19 0.1 membrane-spanning multisubunit translocators of the outer and inner membrane (TOM TOM and TIM respectively 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81931 17015226 105886 20996 11179 SOD1 SOD1 SOD1 1 7.8 Mutant SOD1 associated with or aggregated onto the mitochondrial surface could impede 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81932 17015226 105888 20996 11179 SOD1 SOD1 hSOD1 11 4.2 example ATP synthesis has been reported as unchanged in aged hSOD1 G85R mice ( Damiano et_amp_#xa0 al. 2006 or depleted in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81933 17015226 105888 20996 11179 SOD1 SOD1 hSOD1 24 4.2 ( Damiano et_amp_#xa0 al. 2006 or depleted in late symptomatic hSOD1 G93A mice ( Mattiazzi et_amp_#xa0 al. 2002 or ATP levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81934 17015226 105889 20996 11179 SOD1 SOD1 hSOD1 5 4.2 Creatine which extended survival in hSOD1 G93A mice by alleviating presumed energy deficits ( Browne et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81935 17015226 105892 20996 11179 SOD1 SOD1 SOD1 8 7.8 Early impairment in mitochondrial calcium-buffering capacity in mutant SOD1 spinal cord prior to symptoms and only in disease-relevant tissues 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81936 17015226 105892 20996 11179 SOD1 SOD1 SOD1 23 7.8 symptoms and only in disease-relevant tissues in two different mutant SOD1 models ( Damiano et_amp_#xa0 al. 2006 is perhaps the most 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81937 17015226 105895 1576 990 BCL2 Bcl-2 Bcl-2 42 1.0 Pasinelli et_amp_#xa0 al. 2000 and lowered levels of the antiapoptotic Bcl-2 have been reported in spinal cord motor neurons of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81938 17015226 105895 20996 11179 SOD1 ALS ALS 52 4.8 Bcl-2 have been reported in spinal cord motor neurons of ALS patients ( Ekegren et_amp_#xa0 al. 1999 and Mu et_amp_#xa0 al. 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81939 17015226 105895 20996 11179 SOD1 SOD1 SOD1 65 7.8 et_amp_#xa0 al. 1999 and Mu et_amp_#xa0 al. 1996 and mutant SOD1 mice ( Gonzalez de Aguilar et_amp_#xa0 al. 2000 and Vukosavic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81940 17015226 105896 20017 10940 SLC1A2 EAAT2 EAAT2 17 2.8 caspase-3 activation in glial cells proteolytically inactivates the glutamate transporter EAAT2 ( Boston-Howes et_amp_#xa0 al. 2006 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81941 17015226 105897 20017 10940 SLC1A2 EAAT2 EAAT2 1 2.8 Since EAAT2 is selectively lost during the disease process and is considered 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81942 17015226 105898 20996 11179 SOD1 SOD1 SOD1 5 7.8 An alternate mechanism in which SOD1 is proposed to interact with Bcl-2 and possibly interferes with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81943 17015226 105898 1576 990 BCL2 Bcl-2 Bcl-2 11 1.0 alternate mechanism in which SOD1 is proposed to interact with Bcl-2 and possibly interferes with Bcl-2 antiapoptotic activity ( Pasinelli et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81944 17015226 105898 1576 990 BCL2 Bcl-2 Bcl-2 16 1.0 is proposed to interact with Bcl-2 and possibly interferes with Bcl-2 antiapoptotic activity ( Pasinelli et_amp_#xa0 al. 2004 is attractive but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81945 17015226 105899 1576 990 BCL2 Bcl-2 Bcl-2 6 1.0 However both constitutively increased expression of Bcl-2 ( Kostic et_amp_#xa0 al. 1997 and virally driven overexpression of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81946 17015226 105899 1576 990 BCL2 Bcl-2 Bcl-2 17 1.0 ( Kostic et_amp_#xa0 al. 1997 and virally driven overexpression of Bcl-2 in motor neurons ( Azzouz et_amp_#xa0 al. 2000 protect motor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81947 17015226 105900 1576 990 BCL2 Bcl-2 Bcl-2 0 1.0 Bcl-2 is unable to similarly rescue motor neuron death in other 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81948 17015226 105900 14282 7739 NEFL NF-L NF-L 24 2.4 wobbler and transgenic mice expressing a point mutation in the NF-L gene ( Coulpier et_amp_#xa0 al. 1996 and Houseweart and Cleveland 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81949 17015226 105901 20996 11179 SOD1 SOD1 SOD1-mediated 24 4.5 spectrum caspase inhibitor ( Li et_amp_#xa0 al. 2000 slowed mutant SOD1-mediated neuronal death disease onset was also delayed in the absence 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81950 17015226 105902 20996 11179 SOD1 ALS ALS 11 4.8 of the Neuromuscular Synapse as the First Cellular Phenotype in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81951 17015226 105904 20996 11179 SOD1 ALS ALS 11 4.8 to the muscle at the neuromuscular junction is lost in ALS mouse models long before motor neuron degeneration or death and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81952 17015226 105905 20996 11179 SOD1 ALS ALS 43 4.8 5 _amp_#x3bc m myelinated axons that are selectively vulnerable in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81953 17015226 105906 20996 11179 SOD1 SOD1 SOD1 27 7.8 different subsets of muscle fibers have different susceptibilities to mutant SOD1 toxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81954 17015226 105907 20996 11179 SOD1 SOD1 SOD1 5 7.8 Specifically in two different mutant SOD1 models the fast-fatiguable motor neurons were shown to be affected 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81955 17015226 105908 20996 11179 SOD1 SOD1 SOD1 16 7.8 followed next with the slow type partially resistant to mutant SOD1 and actually attempting to reinnervate previously denervated regions ( Frey 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81956 17015226 105910 23581 12499 UBE4A UFD2 UFD2 17 2.1 containing the first 70 residues of the ubiquitination factor UFD2/E4 UFD2 E4 joined to mononucleotide adenylyltransferase (Nmnat), Nmnat an enzyme that 1 JUMiner_v2.2 1 0 0 2 12499 TotalCon:2<>12499|UBE4A|9354|Complete__12500|UBE4B|10277|Complete__<>AvaiableGeneRif=2<>BEST:12499|UBE4A|0.000614203142604953<>ScoreDetail__12499|UBE4A|0.000614203142604953__12500|UBE4B|0.000481135479732168__ 0 0 0 0 0 81957 17015226 105910 14485 17877 NMNAT1 NMNAT Nmnat 22 1.9 ubiquitination factor UFD2/E4 UFD2 E4 joined to mononucleotide adenylyltransferase (Nmnat), Nmnat an enzyme that facilitates nicotinamide adenine dinucleotide (NAD) NAD synthesis 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81958 17015226 105911 20996 11179 SOD1 SOD1 SOD1 43 7.8 s failed to provide a benefit in three different mutant SOD1 models ( Fischer et_amp_#xa0 al. 2005 and Vande Velde et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81959 17015226 105912 20996 11179 SOD1 ALS ALS 8 4.8 Damage within the Axon Compromised Axonal Transport in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81960 17015226 105914 20996 11179 SOD1 SOD1 SOD1 25 7.8 et_amp_#xa0 al. 1984b and Kawamura et_amp_#xa0 al. 1981 and mutant SOD1 mice ( Bruijn et_amp_#xa0 al. 1998 Kong and Xu 1998 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81961 17015226 105915 14282 7739 NEFL NF-L NF-L 7 2.4 Neurofilaments are obligate heteropolymers of NF light (NF-L), NF-L NF medium (NF-M), NF-M and NF heavy (NF-H) NF-H subunits 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81962 17015226 105915 14285 7734 NEFM NF-M NF-M 10 1.9 obligate heteropolymers of NF light (NF-L), NF-L NF medium (NF-M), NF-M and NF heavy (NF-H) NF-H subunits and interestingly transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81963 17015226 105915 14280 7737 NEFH NFH NF-H 14 0.9 (NF-L), NF-L NF medium (NF-M), NF-M and NF heavy (NF-H) NF-H subunits and interestingly transgenic mice expressing a point mutation in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81964 17015226 105915 14282 7739 NEFL NF-L NF-L 25 2.4 subunits and interestingly transgenic mice expressing a point mutation in NF-L develop motor neuron disease ( Lee et_amp_#xa0 al. 1994 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81965 17015226 105916 20996 11179 SOD1 SOD1 SOD1 7 7.8 Neurofilament accumulations are seen early in mutant SOD1 mice ( Kong and Xu 1998 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81966 17015226 105917 14282 7739 NEFL NF-L NF-L 8 2.4 Removal of all axonal neurofilaments by deletion of NF-L substantially prolonged survival of hSOD1 G85R and hSOD1 G37R mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81967 17015226 105917 20996 11179 SOD1 SOD1 hSOD1 13 4.2 axonal neurofilaments by deletion of NF-L substantially prolonged survival of hSOD1 G85R and hSOD1 G37R mice ( Nguyen et_amp_#xa0 al. 2001 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81968 17015226 105917 20996 11179 SOD1 SOD1 hSOD1 16 4.2 deletion of NF-L substantially prolonged survival of hSOD1 G85R and hSOD1 G37R mice ( Nguyen et_amp_#xa0 al. 2001 and Williamson et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81969 17015226 105917 14280 7737 NEFH NFH NF-H 39 0.9 did removal of most axonal neurofilaments by excessive levels of NF-H ( Couillard-Despres et_amp_#xa0 al. 1998 Kong and Xu 2000 and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81970 17015226 105919 14285 7734 NEFM NF-M NF-M 19 1.9 gene replacement to remove the phosphorylated _amp_#x201c tail_amp_#x201d domains of NF-M and NF-H that normally provide intra-axonal crosslinking of adjacent filaments 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81971 17015226 105919 14280 7737 NEFH NFH NF-H 21 0.9 to remove the phosphorylated _amp_#x201c tail_amp_#x201d domains of NF-M and NF-H that normally provide intra-axonal crosslinking of adjacent filaments 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81972 17015226 105920 20996 11179 SOD1 SOD1 SOD1 7 7.8 Absence of those tail domains sharply slows SOD1 mutant-induced disease ( Lobsiger et_amp_#xa0 al. 2005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81973 17015226 105921 20996 11179 SOD1 SOD1 SOD1 15 7.8 deficit of slow axonal transport has been described in mutant SOD1 mice ( Ackerley et_amp_#xa0 al. 2003 Williamson and Cleveland 1999 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81974 17015226 105922 16622 8982 PIK3R4 p150 p150 20 1.3 disease arose from the discovery of a mutation in the p150 Glued subunit of dynactin in a family affected with a 1 JUMiner_v2.2 1 0 0 2 76 TotalCon:4<>76|ABL1|25|Complete__8982|PIK3R4|30849|No_GeneRif__16850|CTR9|9646|Complete__17168|RAB3GAP2|25782|No_GeneRif__<>AvaiableGeneRif=2<>BEST:76|ABL1|0.000392298373180313<>ScoreDetail__16850|CTR9|0.000151125887864591__76|ABL1|0.000392298373180313__ 0 0 0 0 0 81975 17015226 105922 16622 8982 PIK3R4 p150 p150 46 1.3 of lower motor neuron disease ( Puls et_amp_#xa0 al. 2003 p150 Glued is responsible for providing processivity by bridging between microtubules 1 JUMiner_v2.2 1 0 0 2 76 TotalCon:4<>76|ABL1|25|Complete__8982|PIK3R4|30849|No_GeneRif__16850|CTR9|9646|Complete__17168|RAB3GAP2|25782|No_GeneRif__<>AvaiableGeneRif=2<>BEST:76|ABL1|0.000392298373180313<>ScoreDetail__16850|CTR9|0.000151125887864591__76|ABL1|0.000392298373180313__ 0 0 0 0 0 81976 17015226 105924 20996 11179 SOD1 SOD1 hSOD1 19 4.2 2005 or Cra1 ( Teuchert et_amp_#xa0 al. 2006 mutation to hSOD1 G93A mice significantly improves survival 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81977 17015226 105925 20996 11179 SOD1 SOD1 SOD1 4 7.8 This unexpected amelioration of SOD1 mutant toxicity by a mutation expected to alter retrograde axonal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81978 17015226 105927 11157 6323 KIF5A KIF5A KIF5A 22 0.6 CMT type 2A ( Zhao et_amp_#xa0 al. 2001 loss of KIF5A in hereditary spastic paraplegia ( Reid et_amp_#xa0 al. 2002 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81979 17015226 105927 11175 19349 KIF21A KIF21A KIF21A 35 0.6 spastic paraplegia ( Reid et_amp_#xa0 al. 2002 and loss of KIF21A in a rare disorder affecting the oculomotor nerve ( Yamada 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81980 17015226 105928 23868 12649 VAPB ALS8 ALS8 11 3.6 in genes involved in transport of membranous vesicles include the ALS8 gene VAPB ( Nishimura et_amp_#xa0 al. 2004b Rab7 in CMT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81981 17015226 105928 23868 12649 VAPB VAPB VAPB 13 4.2 involved in transport of membranous vesicles include the ALS8 gene VAPB ( Nishimura et_amp_#xa0 al. 2004b Rab7 in CMT type 2B 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81982 17015226 105928 17794 9788 RAB7A RAB7 Rab7 19 1.0 include the ALS8 gene VAPB ( Nishimura et_amp_#xa0 al. 2004b Rab7 in CMT type 2B ( Verhoeven et_amp_#xa0 al. 2003 and 2 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9788|RAB7A|7879|Complete__30513|RAB7B|338382|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 81983 17015226 105928 24018 18652 VPS54 VPS54 Vps54 30 0.6 in CMT type 2B ( Verhoeven et_amp_#xa0 al. 2003 and Vps54 (vacuolar-vesicular vacuolar-vesicular protein sorting 54 which is responsible for cervical 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81984 17015226 105930 20996 11179 SOD1 ALS ALS 4 4.8 Although progressive paralysis in ALS arises from degeneration and death of motor neurons evidence from 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 81985 17015226 105932 20996 11179 SOD1 SOD1 SOD1 18 7.8 caused by mutations in genes that are ubiquitously expressed ( SOD1 and VAPB or expressed in multiple cells types ( VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81986 17015226 105932 23868 12649 VAPB VAPB VAPB 20 4.2 mutations in genes that are ubiquitously expressed ( SOD1 and VAPB or expressed in multiple cells types ( VEGF and ANG 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81987 17015226 105932 23910 12680 VEGFA VEGF VEGF 29 4.3 SOD1 and VAPB or expressed in multiple cells types ( VEGF and ANG 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81988 17015226 105932 694 483 ANG ANG ANG 31 0.6 VAPB or expressed in multiple cells types ( VEGF and ANG 1 JUMiner_v2.2 1 0 0 2 483 TotalCon:2<>483|ANG|283|Complete__333|AGT|183|Complete__<>AvaiableGeneRif=2<>BEST:483|ANG|0.00143498588159052<>ScoreDetail__333|AGT|0.000160367500232792__483|ANG|0.00143498588159052__ 0 0 0 0 0 81989 17015226 105933 20996 11179 SOD1 SOD1 SOD1 20 7.8 type was required for disease came from expression of mutant SOD1 only within motor neurons ( Lino et_amp_#xa0 al. 2002 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81990 17015226 105934 20996 11179 SOD1 SOD1 SOD1 15 7.8 neuron degeneration or death (albeit albeit the expression of mutant SOD1 selectively within motor neurons might have been at levels too 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81991 17015226 105935 20996 11179 SOD1 SOD1 hSOD1 15 4.2 construction and analysis of chimeric mice that were mixtures of hSOD1 mutant-expressing cells and normal cells ( Clement et_amp_#xa0 al. 2003 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81992 17015226 105937 20996 11179 SOD1 SOD1 SOD1 8 7.8 These efforts conclusively demonstrated that expression of mutant SOD1 within individual motor neurons even at levels that cause early 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81993 17015226 105938 20996 11179 SOD1 SOD1 SOD1 10 7.8 analysis of mice carrying a deletable (_amp_#x201c;floxed_amp_#x201d;) _amp_#x201c floxed_amp_#x201d mutant SOD1 gene that can be excised by the action of the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81994 17015226 105939 20996 11179 SOD1 SOD1 SOD1 5 7.8 Excision of the floxed mutant SOD1 gene exclusively within motor neurons (by by action of Cre 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81995 17015226 105940 14285 7734 NEFM NF-M NF-M 38 1.9 and volume after elimination of the tail domains of the NF-M and NF-H subunits Lobsiger et_amp_#xa0 al. 2005 provide extended survival 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81996 17015226 105940 14280 7737 NEFH NFH NF-H 40 0.9 after elimination of the tail domains of the NF-M and NF-H subunits Lobsiger et_amp_#xa0 al. 2005 provide extended survival of SOD1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81997 17015226 105940 20996 11179 SOD1 SOD1 SOD1 51 7.8 NF-H subunits Lobsiger et_amp_#xa0 al. 2005 provide extended survival of SOD1 mutant mice but only by slowing disease onset 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81998 17015226 105941 20996 11179 SOD1 SOD1 SOD1 4 7.8 In contrast diminishing mutant SOD1 levels within microglia and peripheral macrophages (using using a Cre 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 81999 17015226 105941 10731 6149 ITGAM CD11b CD11b 17 1.0 and peripheral macrophages (using using a Cre transgene with a CD11b promoter that is expressed only within the microglia and peripheral 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82000 17015226 105942 20996 11179 SOD1 SOD1 SOD1 19 7.8 was replaced by transplantation of normal bone marrow cells into SOD1 mutant mice that were themselves unable to synthesize their own 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82001 17015226 105942 21160 11241 SPI1 PU.1 PU.1 39 1.0 own myeloid cells due to deletion of the transcription factor PU.1 ( Beers et_amp_#xa0 al. 2006 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82002 17015226 105943 20996 11179 SOD1 SOD1 hSOD1 3 4.2 Transplantation at birth_amp_#xa0 with hSOD1 G93A mutant-expressing myeloid cells (which which populate both the CNS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82003 17015226 105943 20996 11179 SOD1 SOD1 hSOD1 23 4.2 and the periphery produced onset and survival typical of the hSOD1 G93A mutant line 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82004 17015226 105945 20996 11179 SOD1 SOD1 SOD1 6 7.8 Thus both approaches demonstrated that mutant SOD1 within macrophages/microglial macrophages microglial cells accelerates disease progression while mutant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82005 17015226 105946 20996 11179 SOD1 SOD1 SOD1-expressing 3 4.2 Importantly introducing mutant SOD1-expressing microglial cells into control animals did not give rise to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82006 17015226 105946 20996 11179 SOD1 SOD1 SOD1-expressing 20 4.2 not give rise to motor neuron disease demonstrating that mutant SOD1-expressing macrophages/microglial macrophages microglial cells themselves are not sufficient to cause 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82007 17015226 105948 20996 11179 SOD1 SOD1 SOD1 12 7.8 macrophages/microglial macrophages microglial cells in the spinal cord of mutant SOD1 mice have been shown to enter from the periphery during 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82008 17015226 105955 20996 11179 SOD1 ALS ALS 1 4.8 In ALS microglial activation has been described in the brain and spinal 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82009 17015226 105955 20996 11179 SOD1 SOD1 SOD1 49 7.8 al. 2004 and in the spinal cord of different mutant SOD1 mouse models ( Hall et_amp_#xa0 al. 1998 Henkel et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82010 17015226 105957 20996 11179 SOD1 ALS ALS 22 4.8 the immune response have been reported in spinal cords of ALS patients and hSOD1 G93A mice during the disease course ( 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82011 17015226 105957 20996 11179 SOD1 SOD1 hSOD1 25 4.2 have been reported in spinal cords of ALS patients and hSOD1 G93A mice during the disease course ( Henkel et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82012 17015226 105959 20996 11179 SOD1 ALS ALS 7 4.8 Minocycline was potent in increasing survival of ALS mice and reduced microglial activation ( Kriz et_amp_#xa0 al. 2002 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82013 17015226 105963 20996 11179 SOD1 ALS ALS 8 4.8 Either way supported by its beneficial effect in ALS mice minocycline has been proposed for clinical trial ( Gordon 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82014 17015226 105964 17610 9605 PTGS2 COX-2 COX-2 1 1.0 Cyclooxygenase-2 (COX-2), COX-2 produced in abundance by microglia and other inflammatory cells (but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82015 17015226 105964 17610 9605 PTGS2 COX-2 COX-2 28 1.0 a key role in stimulating production of proinflammatory cytokines and COX-2 expression is induced in spinal cords of ALS patients ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82016 17015226 105964 20996 11179 SOD1 ALS ALS 36 4.8 cytokines and COX-2 expression is induced in spinal cords of ALS patients ( Yasojima et_amp_#xa0 al. 2001 and Yiangou et_amp_#xa0 al. 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82017 17015226 105965 17610 9605 PTGS2 COX-2 COX-2 5 1.0 In mice use of a COX-2 inhibitor (celecoxib) celecoxib prolonged survival by slowing disease onset ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82018 17015226 105966 20996 11179 SOD1 ALS ALS 14 4.8 in a human trial failed to provide a benefit in ALS ( Cudkowicz et_amp_#xa0 al. 2006 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82019 17015226 105967 20996 11179 SOD1 ALS ALS 7 4.8 Additional evidence implicating microglia in pathogenesis of ALS arose from forcing activation of the immune system using chronic 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82020 17015226 105967 24053 12728 VWS LPS LPS 21 0.3 of the immune system using chronic administration of lipopolysaccharide (LPS), LPS a well-known microglial activator 1 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 82021 17015226 105968 20996 11179 SOD1 SOD1 SOD1 3 7.8 Such treatment exacerbated SOD1 mutant-mediated disease in mice ( Nguyen et_amp_#xa0 al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82022 17015226 105969 5184 10647 CX3CL1 fractalkine fractalkine 7 1.0 Similarly inducing microglial activation by deleting the fractalkine receptor a cytokine receptor expressed by microglia mildly accelerated neuronal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82023 17015226 105969 20996 11179 SOD1 SOD1 SOD1 21 7.8 receptor expressed by microglia mildly accelerated neuronal loss in mutant SOD1 mice ( Cardona et_amp_#xa0 al. 2006 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82024 17015226 105970 20996 11179 SOD1 SOD1 SOD1 15 7.8 factors have been described in the spinal cords of mutant SOD1 mice even before motor neuron loss ( Elliott 2001 Hensley 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82025 17015226 105971 11629 6493 LAMC2 CSF CSF 2 0.3 Cerebrospinal fluid (CSF) CSF and serum of ALS patients also contain increased levels of 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 82026 17015226 105971 20996 11179 SOD1 ALS ALS 6 4.8 Cerebrospinal fluid (CSF) CSF and serum of ALS patients also contain increased levels of inflammation related factors including 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82027 17015226 105971 3892 6953 CD46 MCP MCP-1_amp_#x3b1 23 0.3 related factors including complement proteins and monocyte chemoattractant protein-1_amp_#x3b1 (MCP-1_amp_#x3b1;; MCP-1_amp_#x3b1 Goldknopf et_amp_#xa0 al. 2006 and Simpson et_amp_#xa0 al. 2004 11 JUMiner_v2.2 1 0 0 2 1474 TotalCon:3<>6953|CD46|4179|Complete__1474|CAPG|822|Complete__32018|C1orf132|388732|No_GeneRif__<>AvaiableGeneRif=2<>BEST:1474|CAPG|0.000443231819443614<>ScoreDetail__6953|CD46|0.000393905652197574__1474|CAPG|0.000443231819443614__ 0 0 0 0 0 82028 17015226 105972 20996 11179 SOD1 SOD1 SOD1 7 7.8 One particularly interesting cytokine upregulated in mutant SOD1 mouse spinal cords which could play a role in motor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82029 17015226 105973 20996 11179 SOD1 SOD1 hSOD1 12 4.2 been shown to be produced in higher levels by adult hSOD1 G93A microglial cells when stimulated with LPS compared to nontransgenic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82030 17015226 105973 24053 12728 VWS LPS LPS 19 0.3 levels by adult hSOD1 G93A microglial cells when stimulated with LPS compared to nontransgenic microglial cells ( Weydt et_amp_#xa0 al. 2004 1 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 82031 17015226 105974 20996 11179 SOD1 SOD1 SOD1 13 7.8 TNF_amp_#x3b1 antagonist yielded a mild increase in survival in mutant SOD1 mice ( West et_amp_#xa0 al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82032 17015226 105976 7333 11920 FAS FAS Fas-ligand 10 0.3 Microglial cells could therefore be an important player in a Fas-ligand (FasL)-induced FasL -induced apoptosis pathway within motor neurons that is 11 JUMiner_v2.2 1 0 0 2 3594 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:3594|FASN|0.000451814336891917<>ScoreDetail__11920|FAS|0.000421359210301957__3594|FASN|0.000451814336891917__ 0 0 0 0 0 82033 17015226 105976 7334 11936 FASLG FasL FasL 11 1.6 could therefore be an important player in a Fas-ligand (FasL)-induced FasL -induced apoptosis pathway within motor neurons that is driven by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82034 17015226 105977 20996 11179 SOD1 SOD1 SOD1 3 7.8 In addition mutant SOD1 which has now been reported to be released by motor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82035 17015226 105979 20996 11179 SOD1 SOD1 SOD1 12 7.8 a partial explanation for the selectivity of motor neurons to SOD1 mutant toxicity has arisen from identification of a motor-neuron-specific cell-death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82036 17015226 105980 20996 11179 SOD1 SOD1 SOD1 11 7.8 surprisingly embryonic motor neurons extracted from spinal cords of mutant SOD1 mice are more susceptible to toxic insults ( Kruman et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82037 17015226 105980 20996 11179 SOD1 SOD1 hSOD1 66 4.2 neurons from normal mice or mice expressing high levels of hSOD1 WT protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82038 17015226 105981 7333 11920 FAS FAS Fas 16 0.3 been proposed as a motor-neuron-specific cell-death pathway downstream of the Fas death receptor 2 JUMiner_v2.2 1 0 0 2 3594 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:3594|FASN|0.000451814336891917<>ScoreDetail__11920|FAS|0.000421359210301957__3594|FASN|0.000451814336891917__ 0 0 0 0 0 82039 17015226 105982 7333 11920 FAS FAS Fas 7 0.3 Increased susceptibility to death triggered by the Fas receptor requires nitric oxide the Fas death domain-associated protein Daxx 2 JUMiner_v2.2 1 0 0 2 3594 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:3594|FASN|0.000451814336891917<>ScoreDetail__11920|FAS|0.000421359210301957__3594|FASN|0.000451814336891917__ 0 0 0 0 0 82040 17015226 105982 7333 11920 FAS FAS Fas 13 0.3 death triggered by the Fas receptor requires nitric oxide the Fas death domain-associated protein Daxx and p38 kinase activation which subsequently 2 JUMiner_v2.2 1 0 0 2 3594 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:3594|FASN|0.000451814336891917<>ScoreDetail__11920|FAS|0.000421359210301957__3594|FASN|0.000451814336891917__ 0 0 0 0 0 82041 17015226 105982 5457 2681 DAXX DAXX Daxx 17 0.8 Fas receptor requires nitric oxide the Fas death domain-associated protein Daxx and p38 kinase activation which subsequently drives nitric oxide production 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82042 17015226 105982 473 1189 AHSA1 p38 p38 19 0.6 requires nitric oxide the Fas death domain-associated protein Daxx and p38 kinase activation which subsequently drives nitric oxide production thus generating 1 JUMiner_v2.2 1 0 0 2 6878 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6878|MAPK4|0.000435694906646352<>ScoreDetail__1189|AHSA1|0.000318084011600711__6878|MAPK4|0.000435694906646352__6871|MAPK1|0.000418345167806658__6876|MAPK14|0.000402539798783752__ 0 0 0 0 0 82043 17015226 105983 20996 11179 SOD1 SOD1 SOD1 6 7.8 Cultured motor neurons from transgenic mutant SOD1 mice have an increased susceptibility to activation of this pathway 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82044 17015226 105983 20996 11179 SOD1 ALS ALS 24 4.8 of this pathway which is apparently also activated in presymptomatic ALS mice ( Raoul et_amp_#xa0 al. 2002 Raoul et_amp_#xa0 al. 2006 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82045 17015226 105984 20996 11179 SOD1 SOD1 SOD1 12 7.8 acceleration of disease by mutant microglia it is plausible that SOD1 mutant-induced release of nitric oxide by microglia drives this death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82046 17015226 105985 20996 11179 SOD1 ALS ALS 2 4.8 Astrocytes in ALS Gatekeepers of Synaptic Glutamate and Excitoxicity 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82047 17015226 105986 20017 10940 SLC1A2 EAAT2 EAAT2 27 2.8 synaptic glutamate through the action of the glial glutamate transporter EAAT2 (also also referred to as GLT-1 in rodents 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82048 17015226 105986 20017 10940 SLC1A2 GLT-1 GLT-1 32 2.8 the glial glutamate transporter EAAT2 (also also referred to as GLT-1 in rodents 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82049 17015226 105990 8790 4572 GRIA2 GLUR2 GluR2 19 1.3 since their glutamate receptors have a lower proportion of the GluR2 subunit ( Van Damme et_amp_#xa0 al. 2002 relative to many 14 JUMiner_v2.2 1 0 0 2 4572 TotalCon:2<>4572|GRIA2|2891|Complete__4594|GRM2|2912|Complete__<>AvaiableGeneRif=2<>BEST:4572|GRIA2|0.000641070121057652<>ScoreDetail__4594|GRM2|0.000228609694317185__4572|GRIA2|0.000641070121057652__ 0 0 0 0 0 82050 17015226 105991 8790 4572 GRIA2 GLUR2 GluR2 8 1.3 Regulation of the Ca 2 permeability properties of GluR2 is due to posttranscriptional RNA editing with only AMPA receptors 14 JUMiner_v2.2 1 0 0 2 4572 TotalCon:2<>4572|GRIA2|2891|Complete__4594|GRM2|2912|Complete__<>AvaiableGeneRif=2<>BEST:4572|GRIA2|0.000641070121057652<>ScoreDetail__4594|GRM2|0.000228609694317185__4572|GRIA2|0.000641070121057652__ 0 0 0 0 0 82051 17015226 105991 8790 4572 GRIA2 GLUR2 GluR2 21 1.3 to posttranscriptional RNA editing with only AMPA receptors containing edited GluR2 resistant to Ca 2 entry 14 JUMiner_v2.2 1 0 0 2 4572 TotalCon:2<>4572|GRIA2|2891|Complete__4594|GRM2|2912|Complete__<>AvaiableGeneRif=2<>BEST:4572|GRIA2|0.000641070121057652<>ScoreDetail__4594|GRM2|0.000228609694317185__4572|GRIA2|0.000641070121057652__ 0 0 0 0 0 82052 17015226 105992 8790 4572 GRIA2 GLUR2 GluR2 3 1.3 Already with low GluR2 levels the efficiency of mRNA editing is reduced in the 14 JUMiner_v2.2 1 0 0 2 4572 TotalCon:2<>4572|GRIA2|2891|Complete__4594|GRM2|2912|Complete__<>AvaiableGeneRif=2<>BEST:4572|GRIA2|0.000641070121057652<>ScoreDetail__4594|GRM2|0.000228609694317185__4572|GRIA2|0.000641070121057652__ 0 0 0 0 0 82053 17015226 105992 20996 11179 SOD1 ALS ALS 19 4.8 editing is reduced in the spinal cord motor neurons of ALS patients compared to controls ( Kawahara et_amp_#xa0 al. 2004 and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82054 17015226 105993 20996 11179 SOD1 SOD1 hSOD1 8 4.2 Altered efficiency of editing was not found in hSOD1 G93A or hSOD1 H46R rats ( Kawahara et_amp_#xa0 al. 2006 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82055 17015226 105993 20996 11179 SOD1 SOD1 hSOD1 11 4.2 efficiency of editing was not found in hSOD1 G93A or hSOD1 H46R rats ( Kawahara et_amp_#xa0 al. 2006 thereby demonstrating that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82056 17015226 105995 8254 4235 GFAP GFAP GFAP 16 2.8 their intermediate filaments (assembled assembled from glial fibrillary acidic protein GFAP and an increase in the number and size of processes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82057 17015226 105996 20996 11179 SOD1 ALS ALS 8 4.8 Astrocyte activation is seen in spinal cords of ALS patients and SOD1 mutant mice ( Hall et_amp_#xa0 al. 1998 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82058 17015226 105996 20996 11179 SOD1 SOD1 SOD1 11 7.8 activation is seen in spinal cords of ALS patients and SOD1 mutant mice ( Hall et_amp_#xa0 al. 1998 Levine et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82059 17015226 105997 20996 11179 SOD1 SOD1 hSOD1 8 4.2 Indeed for mice expressing the dismutase inactive mutant hSOD1 G85R a very prominent early pathology that increases markedly during 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82060 17015226 105997 20996 11179 SOD1 SOD1 SOD1-containing 26 4.2 that increases markedly during disease course is the presence of SOD1-containing inclusions within activated astrocytes ( Bruijn et_amp_#xa0 al. 1997 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82061 17015226 105998 20996 11179 SOD1 SOD1 SOD1 14 7.8 one of the few firm mechanistic links between sporadic and SOD1 mutant-caused ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82062 17015226 105998 20996 11179 SOD1 ALS ALS 16 4.8 the few firm mechanistic links between sporadic and SOD1 mutant-caused ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82063 17015226 105999 20996 11179 SOD1 ALS ALS 14 4.8 been reported in synaptosomes obtained from affected CNS tissues of ALS patients ( Rothstein et_amp_#xa0 al. 1992 and levels of EAAT2 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82064 17015226 105999 20017 10940 SLC1A2 EAAT2 EAAT2 24 2.8 ALS patients ( Rothstein et_amp_#xa0 al. 1992 and levels of EAAT2 are reduced in the motor cortex and spinal cord of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82065 17015226 105999 20996 11179 SOD1 ALS ALS 35 4.8 are reduced in the motor cortex and spinal cord of ALS patients ( Fray et_amp_#xa0 al. 1998 Maragakis et_amp_#xa0 al. 2004 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82066 17015226 105999 20996 11179 SOD1 SOD1 SOD1 58 7.8 1995 and Sasaki et_amp_#xa0 al. 2000 spinal cords of mutant SOD1 mice ( Bruijn et_amp_#xa0 al. 1997 and rats ( Howland 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82067 17015226 106000 20996 11179 SOD1 ALS ALS 7 4.8 This is functionally of consequence for familial ALS in that hSOD1 G93A mice heterozygous for EAAT2 develop earlier-onset 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82068 17015226 106000 20996 11179 SOD1 SOD1 hSOD1 10 4.2 This is functionally of consequence for familial ALS in that hSOD1 G93A mice heterozygous for EAAT2 develop earlier-onset disease ( Pardo 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82069 17015226 106000 20017 10940 SLC1A2 EAAT2 EAAT2 15 2.8 for familial ALS in that hSOD1 G93A mice heterozygous for EAAT2 develop earlier-onset disease ( Pardo et_amp_#xa0 al. 2006 while drugs 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82070 17015226 106000 20017 10940 SLC1A2 EAAT2 EAAT2 28 2.8 disease ( Pardo et_amp_#xa0 al. 2006 while drugs that increase EAAT2 activity extend survival ( Ganel et_amp_#xa0 al. 2006 and Rothstein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82071 17015226 106001 20017 10940 SLC1A2 EAAT2 EAAT2 9 2.8 Indeed screening of FDA-approved drugs for those that_amp_#xa0 could elevate EAAT2 activity has identified_amp_#xa0 a CNS-penetrating _amp_#x3b2 -lactam antibiotic ceftriaxone as_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82072 17015226 106001 20996 11179 SOD1 SOD1 hSOD1 25 4.2 ceftriaxone as_amp_#xa0 a transcriptional inducer that modestly extends survival in hSOD1 G93A mice ( Rothstein et_amp_#xa0 al. 2005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82073 17015226 106002 20996 11179 SOD1 ALS ALS 20 4.8 to underlie the mild slowing of disease course in human ALS from the only FDA-approved treatment (riluzole; riluzole Doble 1996 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82074 17015226 106003 20996 11179 SOD1 ALS ALS 7 4.8 Additional implication for an astrocytic contribution in ALS is demonstration in cell culture that activated astrocytes induce embryonic 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82075 17015226 106003 14373 7808 NGF NGF NGF 25 0.6 astrocytes induce embryonic motor neuron degeneration via their production of NGF which in the presence of low concentrations of nitric oxide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82076 17015226 106003 22562 11917 TNFRSF1B p75 p75 44 1.2 nitric oxide can induce apoptosis of motor neurons through the p75 NTR receptor 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000490977829123761<>ScoreDetail__9527|PSIP1|0.00030679368483751__2557|CUX1|0.000383724016864081__10876|SIGLEC7|0.000490977829123761__11917|TNFRSF1B|0.000326449601947969__ 0 0 0 0 0 82077 17015226 106003 22562 11917 TNFRSF1B NTR NTR 45 0.2 oxide can induce apoptosis of motor neurons through the p75 NTR receptor 5 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14742 8039 NTSR1 0 82078 17015226 106004 20996 11179 SOD1 SOD1 hSOD1 12 4.2 to resting astrocytes activated astrocytes in the spinal cord of hSOD1 G93A mice have increased NGF synthesis ( Pehar et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82079 17015226 106004 14373 7808 NGF NGF NGF 17 0.6 in the spinal cord of hSOD1 G93A mice have increased NGF synthesis ( Pehar et_amp_#xa0 al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82080 17015226 106005 20996 11179 SOD1 ALS ALS 3 4.8 Muscle Involvement in ALS Targets for Therapy 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82081 17015226 106006 20996 11179 SOD1 ALS ALS- 7 4.2 Among the earliest events in the human ALS- and SOD1-mediated disease is withdrawal of the motor axons from 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82082 17015226 106006 20996 11179 SOD1 SOD1 SOD1-mediated 9 4.5 Among the earliest events in the human ALS- and SOD1-mediated disease is withdrawal of the motor axons from the neuromuscular 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82083 17015226 106007 20996 11179 SOD1 ALS ALS 6 4.8 This denervation generates the progressive paralysis of_amp_#xa0 ALS a consequence of which is muscle atrophy ( Cifuentes-Diaz et_amp_#xa0 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82084 17015226 106008 20996 11179 SOD1 SOD1 SOD1 1 7.8 Mutant SOD1 is also expressed by muscle but whether its presence there 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82085 17015226 106009 20996 11179 SOD1 ALS ALS 15 4.8 muscle mass and strength per se can be beneficial in ALS has been attempted by repetitive injection into hSOD1 G93A mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82086 17015226 106009 20996 11179 SOD1 SOD1 hSOD1 23 4.2 beneficial in ALS has been attempted by repetitive injection into hSOD1 G93A mice of an antibody to myostatin a secreted protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82087 17015226 106011 9939 5464 IGF1 IGF1 IGF-1 14 1.2 hypertrophy induced by agents such as insulin-like growth factor-1 (IGF-1) IGF-1 or growth hormone ( Dobrowolny et_amp_#xa0 al. 2005 Kaspar et_amp_#xa0 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82088 17015226 106011 20996 11179 SOD1 ALS ALS 38 4.8 et_amp_#xa0 al. 2005 has led to significant life extensions in ALS transgenic mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82089 17015226 106012 9939 5464 IGF1 IGF1 IGF-1 2 1.2 For the IGF-1 studies not only was there muscle hypertrophy but also concomitant 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82090 17015226 106013 9939 5464 IGF1 IGF1 IGF-1 4 1.2 Although in one instance IGF-1 synthesis was mediated by a transgene expressed only by the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82091 17015226 106013 9939 5464 IGF1 IGF1 IGF-1 29 1.2 al. 2005 it has not been established if the secreted IGF-1 acts on the muscle the motor neuron or both 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82092 17015226 106015 20996 11179 SOD1 ALS ALS 14 4.8 number of studies have shown that exercise is beneficial in ALS transgenic animals ( Kirkinezos et_amp_#xa0 al. 2003 and Veldink et_amp_#xa0 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82093 17015226 106015 9939 5464 IGF1 IGF1 IGF-1 28 1.2 al. 2003 and Veldink et_amp_#xa0 al. 2003 with_amp_#xa0 exercise and IGF-1 exhibiting a synergistic effect resulting in an increase in median 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82094 17015226 106016 20996 11179 SOD1 ALS ALS 13 4.8 this synergism is not known and the relevance for human ALS unclear as no consensus has emerged from several efforts to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82095 17015226 106017 20996 11179 SOD1 ALS ALS 9 4.8 A Model for Selective Vulnerability of Motor Neurons in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82096 17015226 106018 20996 11179 SOD1 ALS ALS 14 4.8 multiple animal models used a determine pathogenic mechanisms in inherited ALS the central insight is that although motor neuron degeneration and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82097 17015226 106022 20996 11179 SOD1 SOD1 SOD1 4 7.8 During this phase mutant SOD1 primarily acts directly within motor neurons with aggregation of misfolded 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82098 17015226 106022 20996 11179 SOD1 SOD1 SOD1 15 7.8 primarily acts directly within motor neurons with aggregation of misfolded SOD1 damaging cellular machinery especially mitochondria so as to inhibit one 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82099 17015226 106024 20996 11179 SOD1 SOD1 SOD1 0 7.8 SOD1 mutant action within the motor neuron is amplified by action 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82100 17015226 106027 20996 11179 SOD1 SOD1 SOD1 1 7.8 Misfolded SOD1 mutant within astrocytes as well as their activation in response 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82101 17015226 106027 20017 10940 SLC1A2 EAAT2 EAAT2 19 2.8 activation in response to neuronal damage induces loss of the EAAT2 glutamate transporter reducing rapid recovery of synaptic glutamate and driving 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82102 17015226 106028 20996 11179 SOD1 SOD1 SOD1 0 7.8 SOD1 mutant action directly within microglial and astrocytic cells may provoke 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82103 17015226 106028 20996 11179 SOD1 SOD1 SOD1 28 7.8 of toxic factors (e.g., e.g. nitric oxide TNF_amp_#x3b1 or mutant SOD1 secreted or released by cell leakage or lysis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82104 17015226 106030 20996 11179 SOD1 SOD1 SOD1 1 7.8 Mutant SOD1 can itself activate microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82105 17015226 106035 20017 10940 SLC1A2 EAAT2 EAAT2 2 2.8 Loss of EAAT2 glutamate transporters from astrocytes drives repetitive firing of glutamate receptors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82106 17015226 106036 20996 11179 SOD1 SOD1 SOD1 9 7.8 Thus selective sensitivity of motor neurons to ubiquitously expressed SOD1 mutants derives from the combination of risk factors shared by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82107 17015226 106038 20996 11179 SOD1 ALS ALS 10 4.8 these mechanisms (which which have also been invoked in sporadic ALS are right and all combine to underlie selective vulnerability 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82108 17015226 106040 20996 11179 SOD1 ALS ALS 4 4.8 Growth Factor Therapies in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82109 17015226 106041 20996 11179 SOD1 ALS ALS 12 4.8 trophic factors has dominated recent efforts in clinical trials in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82110 17015226 106043 9939 5464 IGF1 IGF1 IGF-1 13 1.2 to nearly uniform disappointment providing little or no benefit for IGF-1 ( Borasio et_amp_#xa0 al. 1998 and Lai et_amp_#xa0 al. 1997 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82111 17015226 106043 1624 1033 BDNF BDNF BDNF 27 0.3 1998 and Lai et_amp_#xa0 al. 1997 and no benefit for BDNF ( BDNF Study Group 1999 or CNTF ( ALS CNTF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82112 17015226 106043 1624 1033 BDNF BDNF BDNF 29 0.3 Lai et_amp_#xa0 al. 1997 and no benefit for BDNF ( BDNF Study Group 1999 or CNTF ( ALS CNTF Treatment Study 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82113 17015226 106043 4649 2169 CNTF CNTF CNTF 35 0.3 no benefit for BDNF ( BDNF Study Group 1999 or CNTF ( ALS CNTF Treatment Study Group 1996 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82114 17015226 106043 20996 11179 SOD1 ALS ALS 37 4.8 for BDNF ( BDNF Study Group 1999 or CNTF ( ALS CNTF Treatment Study Group 1996 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82115 17015226 106043 4649 2169 CNTF CNTF CNTF 38 0.3 BDNF ( BDNF Study Group 1999 or CNTF ( ALS CNTF Treatment Study Group 1996 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82116 17015226 106044 20996 11179 SOD1 ALS ALS 12 4.8 the absence of evidence that growth factors were limiting in ALS the weakness of these approaches was insuring adequate delivery to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82117 17015226 106046 1624 1033 BDNF BDNF BDNF 4 0.3 Continuous intrathecal administration of BDNF was found to be without benefit but ICV infusion of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82118 17015226 106046 9939 5464 IGF1 IGF1 IGF-1 15 1.2 was found to be without benefit but ICV infusion of IGF-1 extended survival in mice ( Nagano et_amp_#xa0 al. 2005a and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82119 17015226 106048 38 22 AAVS1 AAV AAV 15 0.3 A an IGF-1-encoding gene was inserted into adenoassociated virus (AAV), AAV a small replication-defective virus that is episomally maintained within the 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 82120 17015226 106050 20996 11179 SOD1 SOD1 hSOD1 8 4.2 Use of this strategy slowed disease progression in hSOD1 G93A mice even when initiated after disease onset ( Kaspar 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82121 17015226 106052 38 22 AAVS1 AAV AAV 2 0.3 The same AAV producing GDNF used in the same manner provided only a 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 82122 17015226 106052 8240 4232 GDNF GDNF GDNF 4 0.9 The same AAV producing GDNF used in the same manner provided only a very modest 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82123 17015226 106052 8240 4232 GDNF GDNF GDNF 26 0.9 ( Kaspar et_amp_#xa0 al. 2003 consistent with prior efforts using GDNF encoded by adenovirus ( Acsadi et_amp_#xa0 al. 2002 or AAV 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82124 17015226 106052 38 22 AAVS1 AAV AAV 36 0.3 GDNF encoded by adenovirus ( Acsadi et_amp_#xa0 al. 2002 or AAV ( Wang et_amp_#xa0 al. 2002 delivered intramuscularly 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 82125 17015226 106053 23910 12680 VEGFA VEGF VEGF 7 4.3 With the potential that variants in the VEGF gene contribute to some examples of ALS ( Table 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82126 17015226 106053 20996 11179 SOD1 ALS ALS 14 4.8 variants in the VEGF gene contribute to some examples of ALS ( Table 1 delivery of an integrating lentivirus encoding VEGF 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82127 17015226 106053 23910 12680 VEGFA VEGF VEGF 25 4.3 ALS ( Table 1 delivery of an integrating lentivirus encoding VEGF (and and pseudocoated so as to be retrogradely transported extended 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82128 17015226 106053 20996 11179 SOD1 SOD1 hSOD1 37 4.2 pseudocoated so as to be retrogradely transported extended survival of hSOD1 G93A mice ( Azzouz et_amp_#xa0 al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82129 17015226 106054 23910 12680 VEGFA VEGF VEGF 8 4.3 So too did continuous ICV infusion of recombinant VEGF protein into the CSF ( Figure_amp_#xa0 4 B disease onset 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82130 17015226 106054 11629 6493 LAMC2 CSF CSF 12 0.3 did continuous ICV infusion of recombinant VEGF protein into the CSF ( Figure_amp_#xa0 4 B disease onset was delayed and survival 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 82131 17015226 106055 23910 12680 VEGFA VEGF VEGF 4 4.3 This ICV delivery of VEGF was especially effective in slowing forelimb paralysis suggestive of a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82132 17015226 106055 23910 12680 VEGFA VEGF VEGF 18 4.3 in slowing forelimb paralysis suggestive of a higher concentration of VEGF closer to the site of infusion 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82133 17015226 106056 23910 12680 VEGFA VEGF VEGF 7 4.3 A modest benefit was seen even when VEGF treatment was initiated after symptomatic onset 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82134 17015226 106057 23910 12680 VEGFA VEGF VEGF 8 4.3 Unresolved is which cells are targeted by this VEGF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82135 17015226 106058 23910 12680 VEGFA VEGF VEGF 4 4.3 Weekly intraperitoneal injection of VEGF also has been reported to slow disease in hSOD1 G93A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82136 17015226 106058 20996 11179 SOD1 SOD1 hSOD1 13 4.2 of VEGF also has been reported to slow disease in hSOD1 G93A mice ( Zheng et_amp_#xa0 al. 2004 raising the possibility 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82137 17015226 106059 20996 11179 SOD1 ALS ALS 3 4.8 Gene Therapies in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82138 17015226 106060 20996 11179 SOD1 ALS ALS 6 4.8 With recognition that the instances of ALS caused by dominant mutation in SOD1 derive from a toxic 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82139 17015226 106060 20996 11179 SOD1 SOD1 SOD1 12 7.8 that the instances of ALS caused by dominant mutation in SOD1 derive from a toxic property of the mutant protein and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82140 17015226 106062 20996 11179 SOD1 SOD1 SOD1 11 7.8 efforts using siRNA to catalyze degradation of the mRNA encoding SOD1 have proven successful in hSOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82141 17015226 106062 20996 11179 SOD1 SOD1 hSOD1 16 4.2 degradation of the mRNA encoding SOD1 have proven successful in hSOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82142 17015226 106064 20996 11179 SOD1 SOD1 SOD1 9 7.8 After retrograde transport to motor neuron cell bodies reducing SOD1 mutant synthesis in motor neurons had a remarkable effect in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82143 17015226 106066 38 22 AAVS1 AAV AAV 13 0.3 disease onset was seen by retrograde delivery of an siRNA-encoding AAV ( Miller et_amp_#xa0 al. 2005 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 82144 17015226 106072 20996 11179 SOD1 SOD1 SOD1 26 7.8 H This approach has been successfully used for lowering mutant SOD1 levels by 50% throughout the brain and at all levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82145 17015226 106072 20996 11179 SOD1 SOD1 hSOD1 42 4.2 brain and at all levels of the spinal cord of hSOD1 G93A rats 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82146 17015226 106075 20996 11179 SOD1 ALS ALS 20 4.8 be an effective dosage-regulatable means of treating neurodegenerative diseases including ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82147 17015226 106077 20996 11179 SOD1 ALS ALS 4 4.8 Stem Cell Therapies in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82148 17015226 106078 20996 11179 SOD1 ALS ALS 9 4.8 The selective age-dependent killing of motor neurons has made ALS one of the poster diseases for cell replacement using stem 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82149 17015226 106087 8240 4232 GDNF GDNF GDNF 24 0.9 grafting of neural stem cells expressing glial-derived neurotrophic factor (GDNF) GDNF into the nerve 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82150 17015226 106089 20996 11179 SOD1 ALS ALS 16 4.8 in a model of chronic motor neuron degeneration such as ALS remains to be determined 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82151 17015226 106090 20996 11179 SOD1 SOD1 hSOD1 3 4.2 Other strategies with hSOD1 G93A mice have used (1) 1 human neural stem cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82152 17015226 106093 20996 11179 SOD1 SOD1 hSOD1 1 4.2 In hSOD1 G93A mice an increase in neural progenitor cell proliferation migration 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82153 17015226 106094 20996 11179 SOD1 SOD1 hSOD1 22 4.2 was initiated on the predominantly symptomatic side of asymmetrically paralyzed hSOD1 G93A rats ( de Hemptinne et_amp_#xa0 al. 2006 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82154 17015226 106095 20996 11179 SOD1 SOD1 hSOD1 30 4.2 cell neuroprogenitor niches of the forebrain has revealed alterations in hSOD1 G93A mice ( Liu and Martin 2006 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82155 17015226 106097 9939 5464 IGF1 IGF1 IGF-1 37 1.2 precursors including those engineered to produce trophic factors such as IGF-1 are now sensible approaches 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82156 17015226 106098 20996 11179 SOD1 ALS ALS-Causing 3 4.2 Figure_amp_#xa0 1._amp_#xa0 Proposed Toxicities of ALS-Causing SOD1 Protein Aggregates 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82157 17015226 106098 20996 11179 SOD1 SOD1 SOD1 4 7.8 Figure_amp_#xa0 1._amp_#xa0 Proposed Toxicities of ALS-Causing SOD1 Protein Aggregates 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82158 17015226 106099 20996 11179 SOD1 SOD1 SOD1-Mediated 1 4.5 Figure_amp_#xa0 2._amp_#xa0 Mutant SOD1-Mediated Damage to Mitochondria 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82159 17015226 106100 20996 11179 SOD1 SOD1 SOD1 15 7.8 Motor Neuron Degeneration and Glial Activation during the Course of SOD1 Mutant-Initiated ALS Disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82160 17015226 106100 20996 11179 SOD1 ALS ALS 17 4.8 Degeneration and Glial Activation during the Course of SOD1 Mutant-Initiated ALS Disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82161 17015226 106101 20996 11179 SOD1 ALS ALS 5 4.8 Figure_amp_#xa0 4._amp_#xa0 New Directions for Therapies in ALS Using Viral Delivery or Direct Infusion into the Brain or 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000885320172874395<>ScoreDetail__5468|IGFALS|0.000464705082286802__11179|SOD1|0.000885320172874395__ 0 0 0 0 0 82222 17018025 106123 10458 6014 IL4 IL-4 IL-4 11 2.7 the neuroprotective mechanism of anti-inflammatory cytokines we applied interleukin-4 (IL-4) IL-4 to primary microglial cultures activated by lipopolysaccharide as well as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82223 17018025 106123 9939 5464 IGF1 IGF1 IGF-1 44 3.5 O 2 _amp_middot _amp_#8722 and decreased insulin-like growth factor-1 (IGF-1) IGF-1 release from microglial cultures and induced motoneuron injury in microglia-motoneuron 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82224 17018025 106125 10458 6014 IL4 IL-4 IL-4 4 2.7 IL_amp_#8722 4 interaction with microglial IL-4 receptors suppressed and nitric oxide release and lessened lipopolysaccharide-induced microglia-mediated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82225 17018025 106127 10458 6014 IL4 IL-4 IL-4 1 2.7 Although IL-4 enhanced release of free IGF-1 from microglia in the absence 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82226 17018025 106127 9939 5464 IGF1 IGF1 IGF-1 6 3.5 Although IL-4 enhanced release of free IGF-1 from microglia in the absence of lipopolysaccharide it did not 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82227 17018025 106127 9939 5464 IGF1 IGF1 IGF-1 19 3.5 in the absence of lipopolysaccharide it did not enhance free IGF-1 release in the presence of lipopolysaccharide 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82228 17018025 106128 10458 6014 IL4 IL-4 IL-4 4 2.7 These data suggest that IL-4 may provide a significant immunomodulatory signal which can protect against 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82229 17018025 106130 20996 11179 SOD1 SOD1 mSOD1 21 1.3 is supported by the fact that selective overexpression of the mSOD1 transgene in neurons is not sufficient to cause motoneuron disease 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82230 17018025 106132 20996 11179 SOD1 ALS ALS 23 1.3 progression of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), ALS Parkinson's disease and Alzheimer's disease (for for review see Block 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000526036006401261<>ScoreDetail__5468|IGFALS|0.000526036006401261__11179|SOD1|0.000515829408284609__ 0 0 0 0 0 82231 17018025 106135 20996 11179 SOD1 ALS ALS 15 1.3 to reduce neuronal injury in disease models of Parkinson's disease ALS and Alzheimer's disease ( Town et al 2002 Angelov et 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000526036006401261<>ScoreDetail__5468|IGFALS|0.000526036006401261__11179|SOD1|0.000515829408284609__ 0 0 0 0 0 82232 17018025 106137 10458 6014 IL4 IL-4 IL-4 9 2.7 We hypothesized that the Th2 lymphocyte-derived anti-inflammatory cytokine interleukin-4 (IL-4) IL-4 may be one of the potential neuroprotective signals 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82233 17018025 106138 10458 6014 IL4 IL-4 IL-4 0 2.7 IL-4 is an important immunosuppressive mediator in the CNS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82234 17018025 106140 10458 6014 IL4 IL-4 IL-4 0 2.7 IL-4 has also been shown to reduce the production of pro-inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82235 17018025 106140 10463 6018 IL6 IL-6 IL-6 14 1.6 shown to reduce the production of pro-inflammatory cytokines such as IL-6 IL-8 tumor necrosis factor-alpha (TNF-A), TNF-A MIP-1A and RANTES in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82236 17018025 106140 10470 6025 IL8 IL-8 IL-8 15 1.3 to reduce the production of pro-inflammatory cytokines such as IL-6 IL-8 tumor necrosis factor-alpha (TNF-A), TNF-A MIP-1A and RANTES in glial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82237 17018025 106140 22551 11892 TNF TNFA TNF-A 19 1.7 pro-inflammatory cytokines such as IL-6 IL-8 tumor necrosis factor-alpha (TNF-A), TNF-A MIP-1A and RANTES in glial cultures treated with lipopolysaccharide or 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82238 17018025 106140 3766 10632 CCL5 RANTES RANTES 22 1.0 as IL-6 IL-8 tumor necrosis factor-alpha (TNF-A), TNF-A MIP-1A and RANTES in glial cultures treated with lipopolysaccharide or IL-1 ( Ledeboer 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82239 17018025 106140 10437 5992 IL1B IL-1 IL-1 30 1.3 MIP-1A and RANTES in glial cultures treated with lipopolysaccharide or IL-1 ( Ledeboer et al 2000 Ehrlich et al 1998 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82240 17018025 106140 3759 10627 CCL3 MIP1A MIP-1A 20 0.3 cytokines such as IL-6 IL-8 tumor necrosis factor-alpha (TNF-A), TNF-A MIP-1A and RANTES in glial cultures treated with lipopolysaccharide or IL-1 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82241 17018025 106141 10458 6014 IL4 IL-4 IL-4 8 2.7 Recently it has been documented that protection of IL-4 was attributed to down-regulation of TNF-A and up-regulation of insulin-like 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82242 17018025 106141 22551 11892 TNF TNFA TNF-A 14 1.7 documented that protection of IL-4 was attributed to down-regulation of TNF-A and up-regulation of insulin-like growth factor 1 (IGF-1) IGF-1 from 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82243 17018025 106141 9939 5464 IGF1 IGF1 IGF-1 22 3.5 of TNF-A and up-regulation of insulin-like growth factor 1 (IGF-1) IGF-1 from microglia ( Butovsky et al 2005 2006 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82244 17018025 106143 10458 6014 IL4 IL-4 IL-4 9 2.7 In the present study we examined the effects of IL-4 in primary microglia cultures and in microglia cocultured with primary 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82245 17018025 106145 9939 5464 IGF1 IGF1 IGF-1 19 3.5 release more nitric oxide and and lower levels of free IGF-1 an active form of the neurotrophic factor 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82246 17018025 106146 10458 6014 IL4 IL-4 IL-4 3 2.7 The addition of IL-4 protected against the activated microglia-mediated motoneuron injury by reducing nitric 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82247 17018025 106147 9939 5464 IGF1 IGF1 IGF-1 6 3.5 This anti-inflammatory cytokine also enhanced free IGF-1 without lipopolysaccharide stimulation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82248 17018025 106148 9939 5464 IGF1 IGF1 IGF-1 10 3.5 However with lipopolysaccharide there was a minimal increase in free IGF-1 yet the cytokine was still neuroprotective 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82249 17018025 106149 1759 1102 BRD1 BRL BRL 9 0.3 Culture media sera and antibiotics were purchased from Gibco BRL (Rockville, Rockville MD USA and all other reagents were from 1 JUMiner_v2.2 1 2 gibco brl 0 0 0 0 0 0 0 0 82250 17018025 106155 3628 25079 CCDC34 L15 L-15 6 0.3 The cells were resuspended in the L-15 culture medium supplemented with sodium bicarbonate (0.2%), 0.2% glucose (3.6 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>25079|CCDC34|91057|No_GeneRif__5748|IGKV1D-16|28901|No_GeneRif__<>AvaiableGeneRif=0<> 0 0 0 0 0 82251 17018025 106161 7361 20442 FBRS FBS FBS 16 0.0 in SATO's medium supplemented with 10% fetal bovine serum (FBS) FBS and seeded in 150 cm 2 flasks at a density 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>20442|FBRS|64319|Complete__13587|FBXO8|26269|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 82252 17018025 106167 10458 6014 IL4 IL-4 IL-4 0 2.7 IL-4 additions were made either 2 h prior to or after 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82253 17018025 106168 10458 6014 IL4 IL-4 IL-4 19 2.7 added to culture medium 1 h after the addition of IL-4 and lipopolysaccharide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82254 17018025 106171 22562 11917 TNFRSF1B p75 p75 20 1.2 with 2% horse serum and further incubated with mouse anti-rat p75 LNTR monoclonal antibody (p75, p75 1 800 Chemicon overnight at 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000480534661141992<>ScoreDetail__9527|PSIP1|0.000321917427774338__2557|CUX1|0.000359430291393616__10876|SIGLEC7|0.000480534661141992__11917|TNFRSF1B|0.000436761423777344__ 0 0 0 0 0 82255 17018025 106171 22562 11917 TNFRSF1B p75 p75 24 1.2 further incubated with mouse anti-rat p75 LNTR monoclonal antibody (p75, p75 1 800 Chemicon overnight at 4_amp_deg C in blocking solution 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000480534661141992<>ScoreDetail__9527|PSIP1|0.000321917427774338__2557|CUX1|0.000359430291393616__10876|SIGLEC7|0.000480534661141992__11917|TNFRSF1B|0.000436761423777344__ 0 0 0 0 0 82256 17018025 106175 22562 11917 TNFRSF1B p75 p75 6 1.2 As a specific marker for motoneurons p75 (the the low-affinity nerve growth factor receptor immunocytochemistry provides a 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000480534661141992<>ScoreDetail__9527|PSIP1|0.000321917427774338__2557|CUX1|0.000359430291393616__10876|SIGLEC7|0.000480534661141992__11917|TNFRSF1B|0.000436761423777344__ 0 0 0 0 0 82257 17018025 106176 22562 11917 TNFRSF1B p75 p75 9 1.2 Motoneuron survival was assessed by direct counting of large p75 positive cells (cell cell bodies > 30 _amp_#x03BC m displaying 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000480534661141992<>ScoreDetail__9527|PSIP1|0.000321917427774338__2557|CUX1|0.000359430291393616__10876|SIGLEC7|0.000480534661141992__11917|TNFRSF1B|0.000436761423777344__ 0 0 0 0 0 82258 17018025 106182 20996 11179 SOD1 SOD SOD-inhibitable 12 1.3 assay The release of superoxide ( was determined by the SOD-inhibitable reduction of ferricytochrome c ( Gao et al 2002 Mayer 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82259 17018025 106183 10458 6014 IL4 IL-4 IL-4 20 2.7 treated with lipopolysaccharide (1 1 ng/mL) ng mL followed by IL-4 (10 10 ng/mL) ng mL 2 h later 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82260 17018025 106185 10458 6014 IL4 IL-4 IL-4 16 2.7 U/mL), U mL lipopolysaccharide (1 1 ng/mL), ng mL and IL-4 (10 10 ng/mL) ng mL in HBSS were then added 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82261 17018025 106191 20996 11179 SOD1 SOD SOD 0 1.6 SOD effectively inhibited the reduction of ferricytochrome c which confirmed that 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82262 17018025 106198 3778 10620 CCL21 ECL ECL 1 0.0 The ECL plus detection system (Amersham Amersham Pharmacia Biotech Piscataway NJ USA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82263 17018025 106202 10460 6015 IL4R IL4R IL-4R 8 1.8 The conditions of PCR were as follows for IL-4R the primers 5'-CCT GTT CCC AGC CAG ACT AC-3' and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82264 17018025 106202 7572 17371 FHL5 ACT ACT 16 0.3 follows for IL-4R the primers 5'-CCT GTT CCC AGC CAG ACT AC-3' and 5'-AGC ACA GAC CTC AGC AAC AA-3' T 1 JUMiner_v2.2 1 2 35 0 2 17371 TotalCon:6<>24157|ACOT7|11332|Complete__17371|FHL5|9457|Complete__16|SERPINA3|12|Complete__17780|ACTBL2|345651|No_GeneRif__144|ACTG1|71|Complete__145|ACTG2|72|Complete__<>AvaiableGeneRif=5<>BEST:17371|FHL5|0.000663206860248865<>ScoreDetail__17371|FHL5|0.000663206860248865__145|ACTG2|0.000493896671877277__24157|ACOT7|0.000449445971408322__144|ACTG1|0.000317923116934336__16|SERPINA3|0.000530363016633887__ 0 0 0 0 0 82265 17018025 106202 22079 11778 TGM2 TGC TGC 38 0.0 59.6_amp_deg C for B-actin the primers 5'-TTG CTG ACA GGA TGC AGA AG-3' and 5'-CAG TGA GGC CAG GAT AGA GC-3' 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82266 17018025 106202 426 318 AGA AGA AGA 39 0.0 C for B-actin the primers 5'-TTG CTG ACA GGA TGC AGA AG-3' and 5'-CAG TGA GGC CAG GAT AGA GC-3' T 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82267 17018025 106202 21860 11592 TBX1 TGA TGA 43 0.0 primers 5'-TTG CTG ACA GGA TGC AGA AG-3' and 5'-CAG TGA GGC CAG GAT AGA GC-3' T m = 59.6_amp_deg C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82268 17018025 106202 8451 13734 GLYAT GAT GAT 46 0.0 ACA GGA TGC AGA AG-3' and 5'-CAG TGA GGC CAG GAT AGA GC-3' T m = 59.6_amp_deg C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82269 17018025 106202 426 318 AGA AGA AGA 47 0.0 GGA TGC AGA AG-3' and 5'-CAG TGA GGC CAG GAT AGA GC-3' T m = 59.6_amp_deg C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82270 17018025 106206 9939 5464 IGF1 IGF1 IGF-1 3 3.5 ELISA for free IGF-1 IGF-1 ELISA Duoset kit (R R _amp_ D Systems Minneapolis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82271 17018025 106206 9939 5464 IGF1 IGF1 IGF-1 4 3.5 ELISA for free IGF-1 IGF-1 ELISA Duoset kit (R R _amp_ D Systems Minneapolis MN 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82272 17018025 106206 9939 5464 IGF1 IGF1 IGF-1 23 3.5 MN USA was used to determine the concentration of free IGF-1 protein in cell culture supernatant 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82273 17018025 106208 9939 5464 IGF1 IGF1 IGF-1 15 3.5 h 100 _amp_#x03BC L of either sample or standard rat IGF-1 (Diagnostic Diagnostic Systems Laboratories Webster TX USA was added to 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82274 17018025 106214 9939 5464 IGF1 IGF1 IGF-1 10 3.5 Lipopolysaccharide-activated microglia increased production of nitric oxide and decreased free IGF-1 In our previous study we demonstrated that nitric oxide plays 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82275 17018025 106215 9939 5464 IGF1 IGF1 IGF-1 7 3.5 In the present experiments levels of free IGF-1 as well as nitric oxide were measured in microglia activated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82276 17018025 106219 9939 5464 IGF1 IGF1 IGF-1 7 3.5 We also assayed the levels of free IGF-1 in microglia cultures given that only free IGF-1 is active 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82277 17018025 106219 9939 5464 IGF1 IGF1 IGF-1 15 3.5 of free IGF-1 in microglia cultures given that only free IGF-1 is active 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82278 17018025 106220 9939 5464 IGF1 IGF1 IGF-1 8 3.5 the presence of 1 _amp_#x03BC;g/mL _amp_#x03BC g mL lipopolysaccharide free IGF-1 concentrations were significantly lower than untreated microglia ( Fig 1b 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82279 17018025 106221 9939 5464 IGF1 IGF1 IGF-1 8 3.5 In MN Mc cocultures lipopolysaccharide decreased free IGF-1 in a dose-dependent manner ( Fig 2b 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82280 17018025 106222 9939 5464 IGF1 IGF1 IGF-1 30 3.5 m MN lipopolysaccharide 1.02 _amp_plusmn 0.10 _amp_#x03BC m and free IGF-1 levels (MN MN only 1.95 _amp_plusmn 0.31 pg/mL, pg mL 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82281 17018025 106222 9939 5464 IGF1 IGF1 IGF-1 56 3.5 were all close to background indicating that nitrite nitrate and IGF-1 were produced by microglia 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82282 17018025 106225 10458 6014 IL4 IL-4 IL-4 0 2.7 IL-4 protected motoneurons from injury induced by activated microglia To determine 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82283 17018025 106225 10458 6014 IL4 IL-4 IL-4 14 2.7 injury induced by activated microglia To determine the effects of IL-4 on microglia-mediated motoneuron injury IL-4 was added to MN Mc 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82284 17018025 106225 10458 6014 IL4 IL-4 IL-4 19 2.7 To determine the effects of IL-4 on microglia-mediated motoneuron injury IL-4 was added to MN Mc cocultures 2 h before the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82285 17018025 106227 10458 6014 IL4 IL-4 IL-4 4 2.7 In the presence of IL-4 (10 10 ng/mL), ng mL neurite length (92.8% 92.8% _amp_plusmn 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82286 17018025 106228 10458 6014 IL4 IL-4 IL-4 15 2.7 of nitrite nitrate increased after 24-h treatment with lipopolysaccharide and IL-4 significantly reduced nitric oxide production even in the presence of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82287 17018025 106230 10458 6014 IL4 IL-4 IL-4 2 2.7 Addition of IL-4 1-10 ng/mL ng mL significantly prevented motoneuron loss induced by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82288 17018025 106231 10458 6014 IL4 IL-4 IL-4 4 2.7 This protective effect of IL-4 was dose-dependent ( Fig 3d 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82289 17018025 106232 10458 6014 IL4 IL-4 IL-4 4 2.7 With increasing concentrations of IL-4 nitrite nitrate levels in the supernatant decreased ( Fig 3e 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82290 17018025 106233 10458 6014 IL4 IL-4 IL-4 3 2.7 To test whether IL-4 has any survival effects on motoneurons alone motoneurons were treated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82291 17018025 106233 10458 6014 IL4 IL-4 IL-4 15 2.7 any survival effects on motoneurons alone motoneurons were treated with IL-4 (10 10 ng/mL) ng mL for 48 h 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82292 17018025 106234 10458 6014 IL4 IL-4 IL-4 5 2.7 The survival of motoneurons with IL-4 (99.93 99.93 _amp_plusmn 2.48% was similar to survival of motoneurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82293 17018025 106234 10458 6014 IL4 IL-4 IL-4 19 2.7 was similar to survival of motoneurons in the absence of IL-4 (100% 100% as control 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82294 17018025 106235 10458 6014 IL4 IL-4 IL-4 1 2.7 Therefore IL-4 had no direct survival effects on motoneurons supporting that the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82295 17018025 106235 10458 6014 IL4 IL-4 IL-4 15 2.7 survival effects on motoneurons supporting that the neuroprotective effects of IL-4 in microglia-motoneuron cocultures are mediated indirectly through microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82296 17018025 106236 10458 6014 IL4 IL-4 IL-4 8 2.7 Nitric oxide was a key factor modulated by IL-4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82297 17018025 106237 10458 6014 IL4 IL-4 IL-4 9 2.7 To provide further evidence that the neuroprotective effects of IL-4 may be mediated by reducing nitric oxide production we plotted 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82298 17018025 106237 10458 6014 IL4 IL-4 IL-4 29 2.7 we plotted the nitrite nitrate content at different concentrations of IL-4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82299 17018025 106238 10458 6014 IL4 IL-4 IL-4 16 2.7 treated with lipopolysaccharide the suppression of nitrite nitrate generation by IL-4 was dose-dependent ( Fig 4a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82300 17018025 106241 14535 7873 NOS2A iNOS iNOS 17 3.7 nitric oxide by up-regulation of inducible nitric oxide synthase (iNOS) iNOS ( Zhao et al 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82301 17018025 106242 10458 6014 IL4 IL-4 IL-4 6 2.7 To further define the mechanisms of IL-4 neuroprotection microglia were treated with lipopolysaccharide in the presence or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82302 17018025 106242 10458 6014 IL4 IL-4 IL-4 19 2.7 were treated with lipopolysaccharide in the presence or absence of IL-4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82303 17018025 106244 14535 7873 NOS2A iNOS iNOS 6 3.7 Figure 5 demonstrates that lipopolysaccharide enhanced iNOS protein expression and IL-4 significantly inhibited iNOS expression induced by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82304 17018025 106244 10458 6014 IL4 IL-4 IL-4 10 2.7 Figure 5 demonstrates that lipopolysaccharide enhanced iNOS protein expression and IL-4 significantly inhibited iNOS expression induced by lipopolysaccharide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82305 17018025 106244 14535 7873 NOS2A iNOS iNOS 13 3.7 that lipopolysaccharide enhanced iNOS protein expression and IL-4 significantly inhibited iNOS expression induced by lipopolysaccharide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82306 17018025 106245 10458 6014 IL4 IL-4 IL-4 6 2.7 Most strikingly the inhibitory effect of IL-4 added 2 h after lipopolysaccharide (lipopolysaccharide lipopolysaccharide IL-4 was even 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82307 17018025 106245 10458 6014 IL4 IL-4 IL-4 14 2.7 effect of IL-4 added 2 h after lipopolysaccharide (lipopolysaccharide lipopolysaccharide IL-4 was even greater than when IL-4 was added 2 h 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82308 17018025 106245 10458 6014 IL4 IL-4 IL-4 20 2.7 after lipopolysaccharide (lipopolysaccharide lipopolysaccharide IL-4 was even greater than when IL-4 was added 2 h before lipopolysaccharide (IL-4 IL-4 lipopolysaccharide ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82309 17018025 106245 10458 6014 IL4 IL-4 IL-4 27 2.7 than when IL-4 was added 2 h before lipopolysaccharide (IL-4 IL-4 lipopolysaccharide ( p _lt_ 0.05 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82310 17018025 106246 10458 6014 IL4 IL-4 IL-4 0 2.7 IL-4 receptor was up-regulated by lipopolysaccharide and IL-4-mediated neuroprotection was increased 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82311 17018025 106246 10458 6014 IL4 IL-4 IL-4-mediated 7 1.3 IL-4 receptor was up-regulated by lipopolysaccharide and IL-4-mediated neuroprotection was increased To help explain why IL-4 was more 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82312 17018025 106246 10458 6014 IL4 IL-4 IL-4 15 2.7 lipopolysaccharide and IL-4-mediated neuroprotection was increased To help explain why IL-4 was more effective when added after lipopolysaccharide (lipopolysaccharide lipopolysaccharide IL-4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82313 17018025 106246 10458 6014 IL4 IL-4 IL-4 25 2.7 IL-4 was more effective when added after lipopolysaccharide (lipopolysaccharide lipopolysaccharide IL-4 expression of IL-4 receptor (IL-4R) IL-4R was assayed by real-time 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82314 17018025 106246 10458 6014 IL4 IL-4 IL-4 28 2.7 effective when added after lipopolysaccharide (lipopolysaccharide lipopolysaccharide IL-4 expression of IL-4 receptor (IL-4R) IL-4R was assayed by real-time RT-PCR in microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82315 17018025 106246 10460 6015 IL4R IL4R IL-4R 30 1.8 after lipopolysaccharide (lipopolysaccharide lipopolysaccharide IL-4 expression of IL-4 receptor (IL-4R) IL-4R was assayed by real-time RT-PCR in microglia cultures ( Fig 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82316 17018025 106247 10460 6015 IL4R IL4R IL-4R 9 1.8 The addition of lipopolysaccharide significantly increased the expression of IL-4R compared with untreated microglia (9-fold 9-fold increase p _lt_ 0.001 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82317 17018025 106247 10458 6014 IL4 IL-4 IL-4 30 2.7 provides a possible explanation for why adding lipopolysaccharide prior to IL-4 enhanced the protective effects of IL-4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82318 17018025 106247 10458 6014 IL4 IL-4 IL-4 36 2.7 adding lipopolysaccharide prior to IL-4 enhanced the protective effects of IL-4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82319 17018025 106248 10458 6014 IL4 IL-4 IL-4 5 2.7 In the absence of lipopolysaccharide IL-4 did not significantly change IL-4R mRNA levels compared with untreated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82320 17018025 106248 10460 6015 IL4R IL4R IL-4R 10 1.8 In the absence of lipopolysaccharide IL-4 did not significantly change IL-4R mRNA levels compared with untreated control ( p = 0.91 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82321 17018025 106249 10460 6015 IL4R IL4R IL-4R 1 1.8 Furthermore IL-4R mRNA levels were not statistically changed by IL-4 in lipopolysaccharide-activated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82322 17018025 106249 10458 6014 IL4 IL-4 IL-4 9 2.7 Furthermore IL-4R mRNA levels were not statistically changed by IL-4 in lipopolysaccharide-activated microglia (IL-4 IL-4 lipopolysaccharide compared with the group 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82323 17018025 106249 10458 6014 IL4 IL-4 IL-4 13 2.7 were not statistically changed by IL-4 in lipopolysaccharide-activated microglia (IL-4 IL-4 lipopolysaccharide compared with the group treated with lipopolysaccharide only ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82324 17018025 106250 10458 6014 IL4 IL-4 IL-4 3 2.7 Cultures treated with IL-4 2 h after the addition of lipopolysaccharide led to 104.6% 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82325 17018025 106250 10458 6014 IL4 IL-4 IL-4 30 2.7 higher than the motoneuron survival (83.5% 83.5% _amp_plusmn 4.05 when IL-4 was added 2 h prior to the addition of lipopolysaccharide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82326 17018025 106251 10458 6014 IL4 IL-4 IL-4 0 2.7 IL-4 inhibited superoxide production from microglia The effect of the anti-inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82327 17018025 106253 10458 6014 IL4 IL-4 IL-4 0 2.7 IL-4 significantly suppressed the microglial release of in the presence of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82328 17018025 106253 10458 6014 IL4 IL-4 IL-4 16 2.7 release of in the presence of lipopolysaccharide (Mc Mc lipopolysaccharide IL-4 105.6% _amp_plusmn 24.5 vs Mc lipopolysaccharide 183.3% _amp_plusmn 11.8 p 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82329 17018025 106253 10458 6014 IL4 IL-4 IL-4 38 2.7 11.8 p = 0.005 and the level of Mc lipopolysaccharide IL-4 was not significantly different from control ( p = 0.79 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82330 17018025 106254 10458 6014 IL4 IL-4 IL-4 9 2.7 Exogenous nitric oxide and reversed the neuroprotective effects of IL-4 To further prove that neuroprotective effects of IL-4 are through 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82331 17018025 106254 10458 6014 IL4 IL-4 IL-4 17 2.7 effects of IL-4 To further prove that neuroprotective effects of IL-4 are through reducing nitric oxide and release from microglia exogenous 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82332 17018025 106255 10458 6014 IL4 IL-4 IL-4 10 2.7 Figure 8 showed that in the presence of lipopolysaccharide and IL-4 addition of nitric oxide donor (NOC-18, NOC-18 25 _amp_#x03BC m 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82333 17018025 106255 10458 6014 IL4 IL-4 IL-4 56 2.7 exogenous nitric oxide and could reverse the neuroprotective effects of IL-4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82334 17018025 106256 9939 5464 IGF1 IGF1 IGF-1 1 3.5 Free IGF-1 did not increase after addition of IL-4 to lipopolysaccharide-activated microglia 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82335 17018025 106256 10458 6014 IL4 IL-4 IL-4 8 2.7 Free IGF-1 did not increase after addition of IL-4 to lipopolysaccharide-activated microglia In Fig 1b we noted less free 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82336 17018025 106256 9939 5464 IGF1 IGF1 IGF-1 20 3.5 to lipopolysaccharide-activated microglia In Fig 1b we noted less free IGF-1 in the culture media following microglial activation with lipopolysaccharide 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82337 17018025 106257 9939 5464 IGF1 IGF1 IGF-1 3 3.5 To determine whether IGF-1 production was influenced by IL-4 the levels of free IGF-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82338 17018025 106257 10458 6014 IL4 IL-4 IL-4 8 2.7 To determine whether IGF-1 production was influenced by IL-4 the levels of free IGF-1 were measured in microglia monocultures 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82339 17018025 106257 9939 5464 IGF1 IGF1 IGF-1 13 3.5 IGF-1 production was influenced by IL-4 the levels of free IGF-1 were measured in microglia monocultures or MN Mc cocultures 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82340 17018025 106258 10458 6014 IL4 IL-4 IL-4 4 2.7 In cultures without lipopolysaccharide IL-4 significantly increased levels of free IGF-1 ( Fig 9a b 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82341 17018025 106258 9939 5464 IGF1 IGF1 IGF-1 10 3.5 In cultures without lipopolysaccharide IL-4 significantly increased levels of free IGF-1 ( Fig 9a b 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82342 17018025 106259 9939 5464 IGF1 IGF1 IGF-1 2 3.5 The free IGF-1 of motoneuron only cultures were close to background level in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82343 17018025 106259 10458 6014 IL4 IL-4 IL-4 18 2.7 close to background level in the presence or absence of IL-4 (data data not shown indicating that microglia were the source 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82344 17018025 106259 9939 5464 IGF1 IGF1 IGF-1 32 3.5 indicating that microglia were the source of the increased free IGF-1 after IL-4 treatment 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82345 17018025 106259 10458 6014 IL4 IL-4 IL-4 34 2.7 microglia were the source of the increased free IGF-1 after IL-4 treatment 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82346 17018025 106260 9939 5464 IGF1 IGF1 IGF-1 5 3.5 However the levels of free IGF-1 did not change significantly in lipopolysaccharide-activated microglia or in MN 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82347 17018025 106260 10458 6014 IL4 IL-4 IL-4 24 2.7 microglia or in MN Mc lipopolysaccharide cocultures regardless of whether IL-4 was added before or after lipopolysaccharide ( Fig 9a b 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82348 17018025 106261 9939 5464 IGF1 IGF1 IGF-1 5 3.5 Similar results were seen when IGF-1 mRNA levels were measured with and without IL-4 (data data 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82349 17018025 106261 10458 6014 IL4 IL-4 IL-4 13 2.7 seen when IGF-1 mRNA levels were measured with and without IL-4 (data data not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82350 17018025 106262 22551 11892 TNF TNFA TNF-A 45 1.7 nitric oxide and superoxide ( pro-inflammatory neurotoxic cytokines such as TNF-A and glutamate ( Gonzalez-Scarano and Baltuch 1999 Bal-Price and Brown 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82351 17018025 106262 18723 10261 ROS1 ROS ROS 31 0.0 several substances implicated in neurotoxicity including reactive oxygen species (ROS), ROS such as nitric oxide and superoxide ( pro-inflammatory neurotoxic cytokines 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82352 17018025 106263 10458 6014 IL4 IL-4 IL-4 8 2.7 The present study demonstrates that the anti-inflammatory cytokine IL-4 can protect motoneurons from injury induced by lipopolysaccharide-activated microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82353 17018025 106265 10458 6014 IL4 IL-4 IL-4 9 2.7 To our knowledge this is the first report that IL-4 has beneficial effects on motoneuron injury mediated by microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82354 17018025 106266 14535 7873 NOS2A iNOS iNOS 8 3.7 In our previous study we demonstrated that special iNOS inhibitor L-NIL significantly reduced nitric oxide production and reversed motoneuron 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82355 17018025 106267 10458 6014 IL4 IL-4 IL-4 25 2.7 nitrite nitrate levels and motoneuron survival in cocultures treated with IL-4 and exogenously added nitric oxide reversed neuroprotection of IL-4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82356 17018025 106267 10458 6014 IL4 IL-4 IL-4 34 2.7 with IL-4 and exogenously added nitric oxide reversed neuroprotection of IL-4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82357 17018025 106268 10458 6014 IL4 IL-4 IL-4 11 2.7 suggest that nitric oxide is a key factor modulated by IL-4 in our cell culture system 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82358 17018025 106269 14535 7873 NOS2A iNOS iNOS 5 3.7 Nitric oxide is synthesized by iNOS in microglia iNOS protein expression was down-regulated by IL-4 in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82359 17018025 106269 14535 7873 NOS2A iNOS iNOS 8 3.7 Nitric oxide is synthesized by iNOS in microglia iNOS protein expression was down-regulated by IL-4 in activated microglia when 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82360 17018025 106269 10458 6014 IL4 IL-4 IL-4 14 2.7 by iNOS in microglia iNOS protein expression was down-regulated by IL-4 in activated microglia when IL-4 was given either before or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82361 17018025 106269 10458 6014 IL4 IL-4 IL-4 19 2.7 protein expression was down-regulated by IL-4 in activated microglia when IL-4 was given either before or after the triggering signal lipopolysaccharide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82362 17018025 106270 10458 6014 IL4 IL-4 IL-4 5 2.7 More strikingly we found that IL-4 increased motoneuron survival to a greater extent when added to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82363 17018025 106271 10458 6014 IL4 IL-4 IL-4 15 2.7 the cause of this increase we examined the levels of IL-4 mRNA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82364 17018025 106272 10460 6015 IL4R IL4R IL-4R 3 1.8 We detected increased IL-4R mRNA levels after microglia were activated with lipopolysaccharide 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82365 17018025 106273 10460 6015 IL4R IL4R IL-4R 5 1.8 Thus the greater expression of IL-4R with the subsequent greater efficacy of the available IL-4 could 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82366 17018025 106273 10458 6014 IL4 IL-4 IL-4 14 2.7 of IL-4R with the subsequent greater efficacy of the available IL-4 could provide one potential explanation of the increased suppressive effects 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82367 17018025 106273 10458 6014 IL4 IL-4 IL-4 26 2.7 provide one potential explanation of the increased suppressive effects of IL-4 on iNOS expression in activated microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82368 17018025 106273 14535 7873 NOS2A iNOS iNOS 28 3.7 potential explanation of the increased suppressive effects of IL-4 on iNOS expression in activated microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82369 17018025 106274 10458 6014 IL4 IL-4 IL-4 8 2.7 Two studies have reported the inhibitory effects of IL-4 on iNOS in lipopolysaccharide-stimulated astrocytes and mixed glial cultures ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82370 17018025 106274 14535 7873 NOS2A iNOS iNOS 10 3.7 Two studies have reported the inhibitory effects of IL-4 on iNOS in lipopolysaccharide-stimulated astrocytes and mixed glial cultures ( Brodie et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82371 17018025 106274 10458 6014 IL4 IL-4 IL-4 39 2.7 although in their studies the cells were all treated with IL-4 first and then stimulated cell with other triggering signals 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82372 17018025 106278 10458 6014 IL4 IL-4 IL-4 4 2.7 Our present findings that IL-4 also inhibits production in lipopolysaccharide-activated microglia and that neuroprotection of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82373 17018025 106278 10458 6014 IL4 IL-4 IL-4 15 2.7 also inhibits production in lipopolysaccharide-activated microglia and that neuroprotection of IL-4 was reversed by exogenous illustrate another potential neuroprotective aspect of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82374 17018025 106280 10458 6014 IL4 IL-4 IL-4 4 2.7 (1995 1995 reported that IL-4 suppressed production in human microglia activated by TNF-A or interferon 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82375 17018025 106280 22551 11892 TNF TNFA TNF-A 12 1.7 reported that IL-4 suppressed production in human microglia activated by TNF-A or interferon (IFN)-G IFN -G 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82376 17018025 106280 9905 5438 IFNG IFN IFN 15 0.3 production in human microglia activated by TNF-A or interferon (IFN)-G IFN -G 1 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000606769139057836<>ScoreDetail__5438|IFNG|0.000561169268071224__5417|IFNA1|0.000606769139057836__ 0 0 0 0 0 82377 17018025 106281 10458 6014 IL4 IL-4 IL-4 5 2.7 It has been shown that IL-4 reduces formation in macrophages via down-regulation of gp9l-phox at the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82378 17018025 106282 20996 11179 SOD1 ALS ALS 18 1.3 been postulated to play a role in the pathogenesis of ALS Alzheimer's disease and Parkinson's disease ( Le et al 2001 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000526036006401261<>ScoreDetail__5468|IGFALS|0.000526036006401261__11179|SOD1|0.000515829408284609__ 0 0 0 0 0 82379 17018025 106285 14535 7873 NOS2A iNOS iNOS 4 3.7 However simultaneous activation of iNOS (to to produce nitric oxide and NADPH oxidase (to to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82380 17018025 106288 10458 6014 IL4 IL-4 IL-4 3 2.7 The ability of IL-4 to suppress the production of both nitric oxide and suggests 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82381 17018025 106288 10458 6014 IL4 IL-4 IL-4 15 2.7 suppress the production of both nitric oxide and suggests that IL-4 can decrease the formation of peroxynitrite 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82382 17018025 106290 22551 11892 TNF TNFA TNF-A 7 1.7 (2005 2005 demonstrated that AB-stimulated microglia released TNF-A and glutamate which synergistically increased NOS expression and activity in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82383 17018025 106290 14535 7873 NOS2A NOS NOS 13 2.7 that AB-stimulated microglia released TNF-A and glutamate which synergistically increased NOS expression and activity in neurons by western blot and immunocytochemistry 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000727038038566696<>ScoreDetail__7873|NOS2A|0.000727038038566696__7872|NOS1|0.000697604289603259__ 0 0 0 0 0 82384 17018025 106291 22551 11892 TNF TNFA TNF-A 19 1.7 2004 we also showed that lipopolysaccharide induced microglia to release TNF-A and higher levels of glutamate (30-40 30-40 _amp_#x03BC m present 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82385 17018025 106292 14535 7873 NOS2A iNOS iNOS 5 3.7 Therefore in addition to microglia iNOS expression neuronal NOS may be another source of nitric oxide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82386 17018025 106292 14535 7873 NOS2A NOS NOS 8 2.7 Therefore in addition to microglia iNOS expression neuronal NOS may be another source of nitric oxide contributing to motoneuron 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000727038038566696<>ScoreDetail__7873|NOS2A|0.000727038038566696__7872|NOS1|0.000697604289603259__ 0 0 0 0 0 82387 17018025 106293 22551 11892 TNF TNFA TNF-A 6 1.7 It has also been shown that TNF-A had neurotoxic effects through up-regulating iNOS nitric oxide and production 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82388 17018025 106293 14535 7873 NOS2A iNOS iNOS 12 3.7 also been shown that TNF-A had neurotoxic effects through up-regulating iNOS nitric oxide and production from microglia ( Kuno et al 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82389 17018025 106294 10458 6014 IL4 IL-4 IL-4 8 2.7 It has also been documented that neuroprotection of IL-4 was attributed to down-regulation of TNF-A ( Butovsky et al 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82390 17018025 106294 22551 11892 TNF TNFA TNF-A 14 1.7 documented that neuroprotection of IL-4 was attributed to down-regulation of TNF-A ( Butovsky et al 2005 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82391 17018025 106295 22551 11892 TNF TNFA TNF-A 10 1.7 In accordance with this we did find lipopolysaccharide dramatically enhanced TNF-A produced by microglia ( Zhao et al 2004 and IL-4 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82392 17018025 106295 10458 6014 IL4 IL-4 IL-4 21 2.7 TNF-A produced by microglia ( Zhao et al 2004 and IL-4 significantly decreased TNF-A levels in MN Mc lipopolysaccharide cocultures (data 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82393 17018025 106295 22551 11892 TNF TNFA TNF-A 24 1.7 microglia ( Zhao et al 2004 and IL-4 significantly decreased TNF-A levels in MN Mc lipopolysaccharide cocultures (data data not shown 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82394 17018025 106296 22551 11892 TNF TNFA TNF-A 3 1.7 Therefore down-regulation of TNF-A is one of mechanisms by which IL-4 inhibited nitric oxide 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82395 17018025 106296 10458 6014 IL4 IL-4 IL-4 10 2.7 Therefore down-regulation of TNF-A is one of mechanisms by which IL-4 inhibited nitric oxide and production and protected motoneurons from microglia-mediated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82396 17018025 106297 10458 6014 IL4 IL-4 IL-4 8 2.7 Another finding in the current study is that IL-4 increased free IGF-1 the active form of this neuroprotective factor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82397 17018025 106297 9939 5464 IGF1 IGF1 IGF-1 11 3.5 finding in the current study is that IL-4 increased free IGF-1 the active form of this neuroprotective factor in untreated microglia 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82398 17018025 106297 9939 5464 IGF1 IGF1 IGF-1 28 3.5 factor in untreated microglia cultures and that lipopolysaccharide decreased free IGF-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82399 17018025 106298 9939 5464 IGF1 IGF1 IGF-1 9 3.5 At first we hypothesized that the induction of free IGF-1 in microglia might be another aspect of IL-4 neuroprotection however 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82400 17018025 106298 10458 6014 IL4 IL-4 IL-4 17 2.7 of free IGF-1 in microglia might be another aspect of IL-4 neuroprotection however our subsequent results suggested it might not be 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82401 17018025 106299 10458 6014 IL4 IL-4 IL-4 0 2.7 IL-4 increased motoneuron survival in both lipopolysaccharide-treated MN Mc cocultures however 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82402 17018025 106299 10458 6014 IL4 IL-4 IL-4 12 2.7 increased motoneuron survival in both lipopolysaccharide-treated MN Mc cocultures however IL-4 did not increase free IGF-1 levels in the same cocultures 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82403 17018025 106299 9939 5464 IGF1 IGF1 IGF-1 17 3.5 lipopolysaccharide-treated MN Mc cocultures however IL-4 did not increase free IGF-1 levels in the same cocultures 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82404 17018025 106300 9939 5464 IGF1 IGF1 IGF-1 7 3.5 In addition we saw no increase in IGF-1 mRNA in these lipopolysaccharide-activated cultures although it has been reported 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82405 17018025 106300 10458 6014 IL4 IL-4 IL-4 19 2.7 in these lipopolysaccharide-activated cultures although it has been reported that IL-4 up-regulated IGF-1 mRNA in both untreated and lipopolysaccharide-activated microglia ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82406 17018025 106300 9939 5464 IGF1 IGF1 IGF-1 21 3.5 lipopolysaccharide-activated cultures although it has been reported that IL-4 up-regulated IGF-1 mRNA in both untreated and lipopolysaccharide-activated microglia ( Butovsky et 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82407 17018025 106301 9939 5464 IGF1 IGF1 IGF-1 4 3.5 Additionally even though free IGF-1 was up-regulated by IL-4 in untreated microglia cocultured with motoneurons 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82408 17018025 106301 10458 6014 IL4 IL-4 IL-4 8 2.7 Additionally even though free IGF-1 was up-regulated by IL-4 in untreated microglia cocultured with motoneurons IL-4 did not increase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82409 17018025 106301 10458 6014 IL4 IL-4 IL-4 15 2.7 was up-regulated by IL-4 in untreated microglia cocultured with motoneurons IL-4 did not increase motoneuron survival under the same conditions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82410 17018025 106302 9939 5464 IGF1 IGF1 IGF-1 9 3.5 Finally we also found a poor correlation between free IGF-1 levels and motoneuron survival in MN Mc cocultures 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82411 17018025 106303 9939 5464 IGF1 IGF1 IGF-1 5 3.5 Therefore these results suggest that IGF-1 may not be the primary mechanism of IL-4 neuroprotection 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82412 17018025 106303 10458 6014 IL4 IL-4 IL-4 13 2.7 suggest that IGF-1 may not be the primary mechanism of IL-4 neuroprotection 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82413 17018025 106305 9939 5464 IGF1 IGF1 IGF-1 1 3.5 Firstly IGF-1 is clearly a generally neuroprotective trophic factor that has been 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82414 17018025 106306 9939 5464 IGF1 IGF1 IGF-1 16 3.5 that there may have been an immediate local increase in IGF-1 that was quickly sequestered by binding proteins it is likely 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82415 17018025 106306 9939 5464 IGF1 IGF1 IGF-1 30 3.5 sequestered by binding proteins it is likely that the free IGF-1 levels induced by IL-4 either before or after lipopolysaccharide in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82416 17018025 106306 10458 6014 IL4 IL-4 IL-4 34 2.7 it is likely that the free IGF-1 levels induced by IL-4 either before or after lipopolysaccharide in our system were not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82417 17018025 106307 9939 5464 IGF1 IGF1 IGF-1 3 3.5 Secondly because free IGF-1 levels are determined by total IGF-1 and the levels of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82418 17018025 106307 9939 5464 IGF1 IGF1 IGF-1 9 3.5 Secondly because free IGF-1 levels are determined by total IGF-1 and the levels of the five known binding proteins ( 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82419 17018025 106307 9939 5464 IGF1 IGF1 IGF-1 32 3.5 et al 2005 there may have been increases in both IGF-1 and one or more of the binding proteins that resulted 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82420 17018025 106307 9939 5464 IGF1 IGF1 IGF-1 49 3.5 binding proteins that resulted in no net change in free IGF-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82421 17018025 106308 9939 5464 IGF1 IGF1 IGF-1 9 3.5 Finally it is possible that neurotrophic factors other than IGF-1 may enhance the neuroprotective actions of this anti-inflammatory cytokine 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82422 17018025 106309 10458 6014 IL4 IL-4 IL-4 8 2.7 Several studies have demonstrated the beneficial effects of IL-4 in the CNS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82423 17018025 106311 10458 6014 IL4 IL-4 IL-4 4 2.7 (1993 1993 reported that IL-4 blocked microglia-mediated cerebral neuron injury 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82424 17018025 106312 10458 6014 IL4 IL-4 IL-4 6 2.7 It has also been reported that IL-4 increased neuronal survival in hippocampal mixed cultures ( Araujo and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82425 17018025 106313 10458 6014 IL4 IL-4 IL-4 0 2.7 IL-4 delivered by transfected cells inhibited the progression and the severity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82426 17018025 106314 10458 6014 IL4 IL-4 IL-4 4 2.7 Furthermore gene transfer of IL-4 to the retina enhanced the survival of axotomized retinal ganglion 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82427 17018025 106315 10458 6014 IL4 IL-4 IL-4 5 2.7 While these studies demonstrate that IL-4 can be neuroprotective few studies have examined the mechanisms of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82428 17018025 106316 10458 6014 IL4 IL-4 IL-4 6 2.7 Our present study provides evidence that IL-4 protects motoneurons from injury partly by decreasing free radicals released 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82429 17018025 106316 9939 5464 IGF1 IGF1 IGF-1 24 3.5 free radicals released from microglia and may not involve free IGF-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82430 17018025 106317 10458 6014 IL4 IL-4 IL-4 5 2.7 Whereas one paper reported that IL-4 did not significantly suppress nitric oxide production from microglia when 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82431 17018025 106317 9905 5438 IFNG IFNG IFN-G 23 0.3 from microglia when given 24 h after the triggering signals IFN-G and lipopolysaccharide ( Chao et al 1993 we found that 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82432 17018025 106317 10458 6014 IL4 IL-4 IL-4 35 2.7 and lipopolysaccharide ( Chao et al 1993 we found that IL-4 was more neuroprotective when added 2 h after lipopolysaccharide than 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82433 17018025 106319 10458 6014 IL4 IL-4 IL-4 1 2.7 Besides IL-4 IL-10 and transforming growth factor-beta (TGF-B) TGF-B are two other 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82434 17018025 106319 10480 5962 IL10 IL-10 IL-10 2 1.3 Besides IL-4 IL-10 and transforming growth factor-beta (TGF-B) TGF-B are two other major 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82435 17018025 106319 22059 11766 TGFB1 TGFB TGF-B 7 2.2 Besides IL-4 IL-10 and transforming growth factor-beta (TGF-B) TGF-B are two other major anti-inflammatory cytokines 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82436 17018025 106320 10480 5962 IL10 IL-10 IL-10 6 1.3 We had detected the effects of IL-10 and TGF-B in our MN Mc coculture system as well 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82437 17018025 106320 22059 11766 TGFB1 TGFB TGF-B 8 2.2 We had detected the effects of IL-10 and TGF-B in our MN Mc coculture system as well as IL-4 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82438 17018025 106320 10458 6014 IL4 IL-4 IL-4 19 2.7 TGF-B in our MN Mc coculture system as well as IL-4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82439 17018025 106321 22059 11766 TGFB1 TGFB TGF-B 8 2.2 We did not observe a neuroprotective effect of TGF-B in the cultures (data data not shown 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82440 17018025 106322 10458 6014 IL4 IL-4 IL-4 3 2.7 We found that IL-4 had stronger protective effects on motoneurons than IL-10 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82441 17018025 106322 10480 5962 IL10 IL-10 IL-10 11 1.3 found that IL-4 had stronger protective effects on motoneurons than IL-10 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82442 17018025 106323 10458 6014 IL4 IL-4 IL-4 1 2.7 Like IL-4 IL-10 inhibited iNOS expression and nitric oxide production from microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82443 17018025 106323 10480 5962 IL10 IL-10 IL-10 2 1.3 Like IL-4 IL-10 inhibited iNOS expression and nitric oxide production from microglia (data 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82444 17018025 106323 14535 7873 NOS2A iNOS iNOS 4 3.7 Like IL-4 IL-10 inhibited iNOS expression and nitric oxide production from microglia (data data not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82445 17018025 106324 10480 5962 IL10 IL-10 IL-10 1 1.3 However IL-10 increased microglial release and also decreased rather than increased IGF-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82446 17018025 106324 9939 5464 IGF1 IGF1 IGF-1 11 3.5 IL-10 increased microglial release and also decreased rather than increased IGF-1 release from microglia (data data not shown 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82447 17018025 106325 10480 5962 IL10 IL-10 IL-10 10 1.3 Further studies are clearly necessary to define the mechanism of IL-10 effects 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82448 17018025 106326 10458 6014 IL4 IL-4 IL-4 7 2.7 One potential source of the neuroprotective signal IL-4 is Th2 lymphocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82449 17018025 106329 20996 11179 SOD1 ALS ALS 25 1.3 self-reactive T cells was neuroprotective in a transgenic model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000526036006401261<>ScoreDetail__5468|IGFALS|0.000526036006401261__11179|SOD1|0.000515829408284609__ 0 0 0 0 0 82450 17018025 106331 3865 1678 CD4 CD4 CD4 1 0.3 Furthermore CD4 T cells have been documented to enhance facial motoneuron survival 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82451 17018025 106333 10458 6014 IL4 IL-4 IL-4 5 2.7 Our present data suggest that IL-4 may be one of the significant signals in T-cell-mediated neuroprotection 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82452 17018025 106334 10458 6014 IL4 IL-4 IL-4 14 2.7 increase the presence of Th2 lymphocytes and the release of IL-4 would be a promising direction for treatment of neurodegenerative disorders 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 82453 17018025 106337 10458 6014 IL4 IL-4 IL-4 10 2.7 In vivo studies will clearly be required to determine whether IL-4 achieves neuroprotection by mitigating the neurotoxic effects of microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 83587 17034351 107852 20996 11179 SOD1 ALS ALS 7 1.4 Mouse models of familial amyotrophic lateral sclerosis (ALS) ALS based on overexpressed mutant human Cu Zn-superoxide dismutase (SOD1) SOD1 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00163377962594661<>ScoreDetail__5468|IGFALS|0.000363664701145544__11179|SOD1|0.00163377962594661__ 0 0 0 0 0 83588 17034351 107852 20996 11179 SOD1 SOD1 SOD1 16 1.4 ALS based on overexpressed mutant human Cu Zn-superoxide dismutase (SOD1) SOD1 are cases in point 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 83589 17034351 107856 20996 11179 SOD1 SOD1 SOD1 7 1.4 Lesions to redox signal-transduction pathways in mutant SOD1 glial cells may stimulate broad-spectrum upregulation of proinflammatory genes including 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 83590 17034351 107856 14533 7872 NOS1 NOS NOS 30 1.2 (COX-II) COX-II and 5-lipoxygenase (5LOX)]; 5LOX nitric oxide synthase (NOS) NOS isoforms cytokines (particularly particularly tumor necrosis factor alpha TNF-alpha chemokines 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000576435450780223<>ScoreDetail__7873|NOS2A|0.000576435450780223__7872|NOS1|0.000567781649172993__ 0 0 0 0 0 83591 17034351 107856 22551 11892 TNF TNF-alpha TNF-alpha 38 2.7 (NOS) NOS isoforms cytokines (particularly particularly tumor necrosis factor alpha TNF-alpha chemokines and immunoglobulin Fc receptors (FcgammaRs) FcgammaRs 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 83592 17034351 107858 20996 11179 SOD1 SOD1 SOD1 13 1.4 what has been learned to date from studies of mutant SOD1 transgenic animals and demonstrates that the G93A-SOD1 mouse in particular 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 79604 17114826 102824 3852 1634 CD1A CD1 CD-1 3 0.0 Young male colony CD-1 mice were injected with the adjuvants at doses equivalent to 11 JUMiner_v2.2 1 0 0 2 1636 TotalCon:3<>1634|CD1A|909|Complete__1635|CD1B|910|Complete__1636|CD1C|911|Complete__<>AvaiableGeneRif=3<>BEST:1636|CD1C|0.000411584225099154<>ScoreDetail__1634|CD1A|0.000380054727880815__1636|CD1C|0.000411584225099154__1635|CD1B|0.000340028108990343__ 0 0 0 0 0 79966 17127558 103267 9947 5468 IGFALS ALS ALS 4 0.3 The possible causes of ALS are unknown and multiple biological systems have been implicated 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000976662897090573<>ScoreDetail__5468|IGFALS|0.000976662897090573__11179|SOD1|0.000839868655379314__ 0 0 0 0 0 79967 17127558 103268 9947 5468 IGFALS ALS ALS 19 0.3 expression profiling to evaluate a broad spectrum of systems in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000976662897090573<>ScoreDetail__5468|IGFALS|0.000976662897090573__11179|SOD1|0.000839868655379314__ 0 0 0 0 0 79968 17127558 103269 9947 5468 IGFALS ALS ALS 21 0.3 and adjacent sensory cortex were collected at autopsy from five ALS patients and three normal individuals 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000976662897090573<>ScoreDetail__5468|IGFALS|0.000976662897090573__11179|SOD1|0.000839868655379314__ 0 0 0 0 0 79969 17127558 103271 9947 5468 IGFALS ALS ALS 12 0.3 difference in expression of 275 genes was found in the ALS motor cortex of the genes whose expression was changed 10 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000976662897090573<>ScoreDetail__5468|IGFALS|0.000976662897090573__11179|SOD1|0.000839868655379314__ 0 0 0 0 0 79970 17127558 103272 9947 5468 IGFALS ALS ALS 30 0.3 consistent with the idea of excitotoxicity contributing to neurodegeneration in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000976662897090573<>ScoreDetail__5468|IGFALS|0.000976662897090573__11179|SOD1|0.000839868655379314__ 0 0 0 0 0 79971 17127558 103274 9947 5468 IGFALS ALS ALS 17 0.3 expression patterns between the sensory and motor cortex in the ALS brains 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000976662897090573<>ScoreDetail__5468|IGFALS|0.000976662897090573__11179|SOD1|0.000839868655379314__ 0 0 0 0 0 79972 17127558 103276 9947 5468 IGFALS ALS ALS 18 0.3 gene array data newly acquired motor and sensory cortex of ALS and control cases (n n = 4 each were used 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000976662897090573<>ScoreDetail__5468|IGFALS|0.000976662897090573__11179|SOD1|0.000839868655379314__ 0 0 0 0 0 79973 17127558 103278 9947 5468 IGFALS ALS ALS 12 0.3 profile data reported here are consistent with evidence that the ALS brain is characterized by an environment that is permissive for 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000976662897090573<>ScoreDetail__5468|IGFALS|0.000976662897090573__11179|SOD1|0.000839868655379314__ 0 0 0 0 0 79974 17127558 103279 9947 5468 IGFALS ALS ALS 16 0.3 that a metal imbalance particularly for zinc could exist in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000976662897090573<>ScoreDetail__5468|IGFALS|0.000976662897090573__11179|SOD1|0.000839868655379314__ 0 0 0 0 0 79975 17127558 103280 9947 5468 IGFALS ALS ALS 17 0.3 that is thought to be part of the pathogenesis in ALS there was a notable lack of increase in genes required 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000976662897090573<>ScoreDetail__5468|IGFALS|0.000976662897090573__11179|SOD1|0.000839868655379314__ 0 0 0 0 0 79976 17127558 103281 9947 5468 IGFALS ALS ALS 14 0.3 a conceptual framework in which to consider the possibility that ALS could result from a failure to mount adequate protective responses 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000976662897090573<>ScoreDetail__5468|IGFALS|0.000976662897090573__11179|SOD1|0.000839868655379314__ 0 0 0 0 0 80156 17128115 103759 9947 5468 IGFALS ALS ALS 6 0.3 Other compounds have been tried in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000932157670843983<>ScoreDetail__5468|IGFALS|0.000302038761641077__11179|SOD1|0.000932157670843983__ 0 0 0 0 0 74827 17190960 95976 20996 11179 SOD1 ALS ALS 18 0.0 rare idiosyncratic reaction that can occur with the riluzole in ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000339500933627567<>ScoreDetail__5468|IGFALS|0.000339500933627567__11179|SOD1|0.000247529181602915__ 0 0 0 0 0 74828 17190960 95988 6981 22140 FAM20C RNS RNS 9 0.0 var oas='URL' var RN = new String (Math.random()); Math.random var RNS = RN.substring (2, 2 11 function DisplayAds (position, position sitepage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74829 17190960 95988 6981 22140 FAM20C RNS RNS 27 0.0 position sitepage width height var oaspage= sitepage '/1' ' 1' RNS '@' position if (_version _version ' else document.write (' ' 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74830 17190960 95996 20996 11179 SOD1 ALS ALS 10 0.0 Riluzole is the only Food and Drug Administration-approved treatment of ALS that has been shown to modestly prolong survival 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000339500933627567<>ScoreDetail__5468|IGFALS|0.000339500933627567__11179|SOD1|0.000247529181602915__ 0 0 0 0 0 74831 17190960 96002 20996 11179 SOD1 ALS ALS 14 0.0 life-threatening systemic inflammatory reaction to riluzole in a patient with ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000339500933627567<>ScoreDetail__5468|IGFALS|0.000339500933627567__11179|SOD1|0.000247529181602915__ 0 0 0 0 0 74832 17190960 96003 20996 11179 SOD1 ALS ALS 7 0.0 A healthy 50-year-old man was diagnosed with ALS after presenting with 1 year of progressive asymmetrical hand weakness 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000339500933627567<>ScoreDetail__5468|IGFALS|0.000339500933627567__11179|SOD1|0.000247529181602915__ 0 0 0 0 0 74833 17190960 96004 20996 11179 SOD1 ALS ALS 9 0.0 He fulfilled the El Escorial Criteria for clinically definite ALS at the time of his presentation 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000339500933627567<>ScoreDetail__5468|IGFALS|0.000339500933627567__11179|SOD1|0.000247529181602915__ 0 0 0 0 0 74834 17190960 96008 20172 10933 SLC17A5 AST AST 10 0.0 His liver enzymes at that time demonstrated a modest elevation AST of 92 (normal, normal 12 to 31 alanine aminotransferase of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74863 17191135 96081 18723 10261 ROS1 ROS ROS 6 0.6 However while excess reactive oxygen species (ROS) ROS are toxic regulated ROS play an important role in cell 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 74864 17191135 96081 18723 10261 ROS1 ROS ROS 10 0.6 while excess reactive oxygen species (ROS) ROS are toxic regulated ROS play an important role in cell signaling 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 74865 17191135 96082 6554 3309 ELA2 HNE HNE 20 0.0 of the product of polyunsaturated fatty acid peroxidation (hydroxynonenals, hydroxynonenals HNE or cholesterol oxidation can disrupt redox homeostasis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74866 17191135 96085 18723 10261 ROS1 ROS ROS 18 0.6 is generally associated with metabolic derangements and excessive production of ROS 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 74867 17191135 96093 122 80 ABP1 ABP ABP 8 0.3 Specifically any dietary components that inhibit inappropriate inflammation ABP oligomerization and consequent increased apoptosis are of particular interest with 1 JUMiner_v2.2 1 0 0 2 10839 TotalCon:2<>80|ABP1|26|Complete__10839|SHBG|6462|Complete__<>AvaiableGeneRif=2<>BEST:10839|SHBG|0.00042022616685875<>ScoreDetail__80|ABP1|0.000281036389679619__10839|SHBG|0.00042022616685875__ 0 0 0 0 0 74868 17191135 96096 926 620 APP amyloid amyloid 21 1.3 as a novel nutritional approach to reduce oxidative damage and amyloid pathology in AD 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 74869 17191135 96101 18723 10261 ROS1 ROS ROS 16 0.6 uptake by cells is converted into reactive oxygen species (ROS) ROS 1 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 74870 17191135 96103 18723 10261 ROS1 ROS ROS 9 0.6 In contrast to this physiological role pathological actions of ROS occur at an order of magnitude higher concentrations 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 74871 17191135 96106 18723 10261 ROS1 ROS ROS 5 0.6 Indeed continuous low concentrations of ROS induce expression of antioxidant enzymes and related defense mechanisms 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 74872 17191135 96107 20996 11179 SOD1 ALS ALS 13 1.9 s diseases (HD), HD but also amyotrophic lateral scelrosis (ALS) ALS and Friedreich_amp_#8217 s ataxia (FRDA) FRDA belong to the so-called 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000570340949044605<>ScoreDetail__5468|IGFALS|0.000429859285933318__11179|SOD1|0.000570340949044605__ 0 0 0 0 0 74873 17191135 96107 7975 3951 FXN FRDA FRDA 17 1.5 amyotrophic lateral scelrosis (ALS) ALS and Friedreich_amp_#8217 s ataxia (FRDA) FRDA belong to the so-called _amp_#8220 protein conformational diseases_amp_#8221 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74874 17191135 96111 18723 10261 ROS1 ROS ROS 20 0.6 stress which leads to mitochondrial dysfunction and excessive production of ROS thus inducing oxidative stress 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 74875 17191135 96112 18723 10261 ROS1 ROS ROS 9 0.6 The ability of a cell to deal with excessive ROS as well as excessive reactive nitrogen species (RNS) RNS requires 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 74876 17191135 96112 6981 22140 FAM20C RNS RNS 17 0.6 excessive ROS as well as excessive reactive nitrogen species (RNS) RNS requires the activation of pro-survival pathways as well as the 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 74877 17191135 96113 9462 5013 HMOX1 HO-1 HO-1 2 6.5 Heme oxygenase-1 (HO-1), HO-1 also referred to as Hsp32 belongs to the Hsps family 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74878 17191135 96114 1681 1062 BLVRA BVR BVR 8 0.9 This latter is then reduced by biliverdin reductase (BVR) BVR into bilirubin (BR), BR a linear tetrapyrrole with antioxidant properties 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74879 17191135 96115 6981 22140 FAM20C RNS RNS 21 0.6 stress through its properties to bind and inactivate NO and RNS 11 -14 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 74880 17191135 96116 9462 5013 HMOX1 HO-1 HO-1 12 6.5 1 ( A Cellular stress response and the interplay between HO-1 and TRXr 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74881 17191135 96118 9691 5232 HSPA1A HSP Hsp 0 1.9 Hsp response is also involved in cellular homeostasis during various physiological 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74882 17191135 96120 14345 7782 NFE2L2 NRF2 Nrf2 11 2.1 activation (via via acetylation of the redox sensitive transcription factor Nrf2 and its consequent binding to the antioxidant responsive element (ARE) 2 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 74883 17191135 96120 9462 5013 HMOX1 HO-1 HO-1 27 6.5 antioxidant responsive element (ARE) ARE in the HO gene up-regulates HO-1 and TRXr thus counteracting nitrosative stress and NO-mediated neurotoxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74884 17191135 96121 1493 14078 BACH2 BACH2 Bach-2 12 0.3 same figure are described the respective roles of protein factors Bach-2 (positive) positive and Keap (negative) negative in the Nrf2 activation 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74885 17191135 96121 14345 7782 NFE2L2 NRF2 Nrf2 19 2.1 factors Bach-2 (positive) positive and Keap (negative) negative in the Nrf2 activation as well as the redox cycling between Bilirubin and 2 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 74886 17191135 96121 1681 1062 BLVRA BVR BVR 34 0.9 the redox cycling between Bilirubin and biliverdin through the enzyme BVR 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74887 17191135 96122 9462 5013 HMOX1 HO-1 HO-1 3 6.5 OxS oxidative stress HO-1 heme oxygenase TRXr thioredoxin reductase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74888 17191135 96123 23454 12435 TXN TRX TRX 0 2.5 TRX Thioredoxin SH (reduced reduced form S-S oxidized form 1 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 74889 17191135 96124 9462 5013 HMOX1 HO-1 HO-1 5 6.5 ( B Regulation of HO-1 gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74890 17191135 96125 14345 7782 NFE2L2 NRF2 Nrf2 5 2.1 Nuclear factor-erythroid 2-related factor 2 (Nrf2) Nrf2 is a transcription factor responsible for the induction of several 2 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 74891 17191135 96125 9462 5013 HMOX1 HO-1 HO-1 24 6.5 of several genes related to the cellular stress response including HO-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74892 17191135 96126 14345 7782 NFE2L2 NRF2 Nrf2 3 2.1 Under normal conditions Nrf2 is sequestered in the cytoplasm by an actin-binding protein Kelch-like 2 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 74893 17191135 96126 10983 23177 KEAP1 KEAP1 Keap1 18 0.3 by an actin-binding protein Kelch-like ECH associating protein 1 (Keap1), Keap1 but upon exposure of cells to oxidative stress Nrf2 dissociates 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74894 17191135 96126 14345 7782 NFE2L2 NRF2 Nrf2 27 2.1 (Keap1), Keap1 but upon exposure of cells to oxidative stress Nrf2 dissociates from Keap1 translocates to the nucleus binds to antioxidant 2 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 74895 17191135 96126 10983 23177 KEAP1 KEAP1 Keap1 30 0.3 upon exposure of cells to oxidative stress Nrf2 dissociates from Keap1 translocates to the nucleus binds to antioxidant responsive elements (AREs), 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74896 17191135 96126 9462 5013 HMOX1 HO-1 HO-1 43 6.5 nucleus binds to antioxidant responsive elements (AREs), AREs and activates HO-1 gene This review will emphasize the role of free radicals 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74897 17191135 96127 9462 5013 HMOX1 HO-1 HO-1 14 6.5 role played by members of the vitagene system such as HO-1 and Thioredoxin (Fig Fig 1 A in modulating the onset 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74898 17191135 96135 18723 10261 ROS1 ROS ROS 6 0.6 As a consequence of this aggregation ROS formation increases and a pro-oxidant environment takes place 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 74899 17191135 96139 20997 11180 SOD2 Mn-SOD Mn-SOD 14 1.9 genes such as heme oxygenase thioredoxin and detoxificant enzymes (Mn-SOD, Mn-SOD glutathione S-transferase NADPH quinone reductase cytokine immunoreceptors and growth factors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74900 17191135 96140 18723 10261 ROS1 ROS ROS 13 0.6 heme oxygenase could _amp_#8220 sense_amp_#8221 NO and thus protect against ROS and RNS insults is supported by the following findings (a) 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 74901 17191135 96140 6981 22140 FAM20C RNS RNS 15 0.6 could _amp_#8220 sense_amp_#8221 NO and thus protect against ROS and RNS insults is supported by the following findings (a) a NO 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 74902 17191135 96140 9462 5013 HMOX1 HO-1 HO-1 29 6.5 the following findings (a) a NO and NO-related species induce HO-1 expression and increase heme oxygenase activity in human glioblastoma cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74903 17191135 96141 6981 22140 FAM20C RNS RNS 5 0.6 The conception that NO and RNS can be directly involved in the modulation of HO-1 expression 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 74904 17191135 96141 9462 5013 HMOX1 HO-1 HO-1 14 6.5 and RNS can be directly involved in the modulation of HO-1 expression in eukaryotes is based on the evidence that different 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74905 17191135 96141 9462 5013 HMOX1 HO-1 HO-1 30 6.5 on the evidence that different NO-releasing agents can markedly increase HO-1 and Hsp70 in a variety of tissues including brain cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74906 17191135 96141 9691 5232 HSPA1A HSP70 Hsp70 32 3.5 evidence that different NO-releasing agents can markedly increase HO-1 and Hsp70 in a variety of tissues including brain cells 19 20 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74907 17191135 96142 10676 6121 IRF6 LPS LPS 7 0.6 In rat glial cells treatment with lipopolysaccaride (LPS) LPS and interferon-G (IFN-G) IFN-G promotes a rapid increase in both 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 74908 17191135 96142 9905 5438 IFNG IFNG IFN-G 10 0.8 glial cells treatment with lipopolysaccaride (LPS) LPS and interferon-G (IFN-G) IFN-G promotes a rapid increase in both iNOS expression and nitrite 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74909 17191135 96142 14535 7873 NOS2A iNOS iNOS 17 3.2 and interferon-G (IFN-G) IFN-G promotes a rapid increase in both iNOS expression and nitrite levels followed by enhancement of Hsp70 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74910 17191135 96142 9691 5232 HSPA1A HSP70 Hsp70 26 3.5 both iNOS expression and nitrite levels followed by enhancement of Hsp70 3 20 whereas the modulation of HO-1 mRNA expression by 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74911 17191135 96142 9462 5013 HMOX1 HO-1 HO-1 36 6.5 by enhancement of Hsp70 3 20 whereas the modulation of HO-1 mRNA expression by iNOS-derived NO following stimulation with LPS has 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74912 17191135 96142 14535 7873 NOS2A iNOS iNOS-derived 40 2.7 3 20 whereas the modulation of HO-1 mRNA expression by iNOS-derived NO following stimulation with LPS has also been reported in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74913 17191135 96142 10676 6121 IRF6 LPS LPS 45 0.6 of HO-1 mRNA expression by iNOS-derived NO following stimulation with LPS has also been reported in different brain regions particularly in 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 74914 17191135 96143 14535 7873 NOS2A iNOS iNOS 5 3.2 Moreover the early increase in iNOS protein levels observed in endothelial cells exposed to low oxygen 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74915 17191135 96143 9462 5013 HMOX1 HO-1 HO-1 23 6.5 to low oxygen tension seems to precede the stimulation of HO-1 expression and activity an effect that appears to be finely 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74916 17191135 96144 9462 5013 HMOX1 HO-1 HO-1 25 6.5 molecule which by triggering expression of cytoprotective genes such as HO-1 and Hsp70 may lead to adaptation and resistance of brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74917 17191135 96144 9691 5232 HSPA1A HSP70 Hsp70 27 3.5 by triggering expression of cytoprotective genes such as HO-1 and Hsp70 may lead to adaptation and resistance of brain cells to 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74918 17191135 96145 9462 5013 HMOX1 HO-1 HO-1 20 6.5 sites within the promoter and distal enhancer regions of the HO-1 gene such as Fos/Jun Fos Jun activator protein-1 (AP-1)], AP-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74919 17191135 96145 7683 3796 FOS FOS Fos 24 1.8 distal enhancer regions of the HO-1 gene such as Fos/Jun Fos Jun activator protein-1 (AP-1)], AP-1 nuclear factor-kB (NFkB) NFkB and 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74920 17191135 96145 10824 6204 JUN AP-1 AP-1 27 1.6 HO-1 gene such as Fos/Jun Fos Jun activator protein-1 (AP-1)], AP-1 nuclear factor-kB (NFkB) NFkB and the more recently identified Nrf2 1 JUMiner_v2.2 1 0 0 2 6204 TotalCon:5<>3796|FOS|2353|Complete__3797|FOSB|2354|Complete__6204|JUN|3725|Complete__6205|JUNB|3726|Complete__6206|JUND|3727|Complete__<>AvaiableGeneRif=5<>BEST:6204|JUN|0.00077545260429419<>ScoreDetail__3796|FOS|0.000631914674627876__3797|FOSB|0.000554782843078888__6205|JUNB|0.00063223039517478__6204|JUN|0.00077545260429419__6206|JUND|0.00070916977257676__ 0 0 0 0 0 74921 17191135 96145 14352 7794 NFKB1 NFKB NFkB 30 0.6 Fos/Jun Fos Jun activator protein-1 (AP-1)], AP-1 nuclear factor-kB (NFkB) NFkB and the more recently identified Nrf2 proteins 24 -26 (Fig 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74922 17191135 96145 14345 7782 NFE2L2 NRF2 Nrf2 36 2.1 AP-1 nuclear factor-kB (NFkB) NFkB and the more recently identified Nrf2 proteins 24 -26 (Fig Fig 1 B contain cysteine residues 2 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 74923 17191135 96147 9462 5013 HMOX1 HO-1 HO-1 22 6.5 and complex IV inhibition an effect associated with up-regulation of HO-1 and nuclear translocation of the transcription factor Nrf-2 27 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74924 17191135 96147 14345 7782 NFE2L2 NRF2 Nrf-2 30 1.6 up-regulation of HO-1 and nuclear translocation of the transcription factor Nrf-2 27 1 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 74925 17191135 96156 9726 5269 HSPE1 HSP10 Hsp10 7 1.9 Some of the known Hsps include ubiquitin Hsp10 Hsp27 Hsp32 (or or HO-1 Hsp47 Hsp60 Hsc70 Hsp70 (or 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74926 17191135 96156 9708 5247 HSPB2 HSP27 Hsp27 8 1.9 Some of the known Hsps include ubiquitin Hsp10 Hsp27 Hsp32 (or or HO-1 Hsp47 Hsp60 Hsc70 Hsp70 (or or 2 JUMiner_v2.2 1 0 0 2 5246 TotalCon:2<>5246|HSPB1|3315|Complete__5247|HSPB2|3316|Complete__<>AvaiableGeneRif=2<>BEST:5246|HSPB1|0.000908602424758586<>ScoreDetail__5246|HSPB1|0.000908602424758586__5247|HSPB2|0.000783297072361479__ 0 0 0 0 0 74927 17191135 96156 9462 5013 HMOX1 HO-1 HO-1 11 6.5 the known Hsps include ubiquitin Hsp10 Hsp27 Hsp32 (or or HO-1 Hsp47 Hsp60 Hsc70 Hsp70 (or or Hsp72 Hsp90 and Hsp100/105 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74928 17191135 96156 19730 1546 SERPINH1 HSP47 Hsp47 12 1.3 known Hsps include ubiquitin Hsp10 Hsp27 Hsp32 (or or HO-1 Hsp47 Hsp60 Hsc70 Hsp70 (or or Hsp72 Hsp90 and Hsp100/105 Hsp100 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74929 17191135 96156 9718 5261 HSPD1 HSP60 Hsp60 13 1.9 Hsps include ubiquitin Hsp10 Hsp27 Hsp32 (or or HO-1 Hsp47 Hsp60 Hsc70 Hsp70 (or or Hsp72 Hsp90 and Hsp100/105 Hsp100 105 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74930 17191135 96156 9700 5241 HSPA8 HSC70 Hsc70 14 1.9 include ubiquitin Hsp10 Hsp27 Hsp32 (or or HO-1 Hsp47 Hsp60 Hsc70 Hsp70 (or or Hsp72 Hsp90 and Hsp100/105 Hsp100 105 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74931 17191135 96156 9691 5232 HSPA1A HSP70 Hsp70 15 3.5 ubiquitin Hsp10 Hsp27 Hsp32 (or or HO-1 Hsp47 Hsp60 Hsc70 Hsp70 (or or Hsp72 Hsp90 and Hsp100/105 Hsp100 105 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74932 17191135 96156 9691 5232 HSPA1A HSP72 Hsp72 17 2.9 Hsp32 (or or HO-1 Hsp47 Hsp60 Hsc70 Hsp70 (or or Hsp72 Hsp90 and Hsp100/105 Hsp100 105 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74933 17191135 96156 9676 5253 HSP90AA1 Hsp90 Hsp90 18 3.4 (or or HO-1 Hsp47 Hsp60 Hsc70 Hsp70 (or or Hsp72 Hsp90 and Hsp100/105 Hsp100 105 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74934 17191135 96159 9700 5241 HSPA8 HSC70 Hsc70 5 1.9 Included in this family are Hsc70 (heat heat shock cognate the constitutive form Hsp70 (the the 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74935 17191135 96159 9691 5232 HSPA1A HSP70 Hsp70 12 3.5 family are Hsc70 (heat heat shock cognate the constitutive form Hsp70 (the the inducible form also referred to as Hsp72 GRP75 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74936 17191135 96159 9691 5232 HSPA1A HSP72 Hsp72 20 2.9 form Hsp70 (the the inducible form also referred to as Hsp72 GRP75 (a a constitutively expressed glucose-regulated protein found in the 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74937 17191135 96159 9701 5244 HSPA9 GRP75 GRP75 21 1.9 Hsp70 (the the inducible form also referred to as Hsp72 GRP75 (a a constitutively expressed glucose-regulated protein found in the endoplasmic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74938 17191135 96160 9691 5232 HSPA1A HSP70 Hsp70 9 3.5 After a variety of central nervous system (CNS) CNS insults Hsp70 is synthesized at high levels and is present in cytosol 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74939 17191135 96162 10463 6018 IL6 HSF HSFs 7 0.3 These denaturated proteins activate heat shock factors (HSFs) HSFs within the cytosol (or or ER by dissociating other Hsps 13 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 74940 17191135 96162 10463 6018 IL6 HSF HSF 20 0.3 (or or ER by dissociating other Hsps normally bound to HSF 34 13 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 74941 17191135 96163 10463 6018 IL6 HSF HSF 1 0.3 Freed HSF is phosphorylated and forms trimers which enter the nucleus and 13 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 74942 17191135 96163 9652 23316 HSD17B6 HSE HSE 17 0.0 enter the nucleus and bind to heat shock elements (HSE) HSE within the promoters of different heat shock genes leading to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74943 17191135 96164 9691 5232 HSPA1A HSP70 Hsp70 5 3.5 After heat shock synthesis of Hsp70 may increase to become the most abundant protein in the 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74944 17191135 96165 9691 5232 HSPA1A HSP70 Hsp70 2 3.5 Once synthesized Hsp70 binds to denaturated proteins in an ATP-dependent manner 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74945 17191135 96168 9691 5232 HSPA1A HSP70 Hsp70 18 3.5 cytokine-induced nitrosative stress is associated with an increased synthesis of Hsp70 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74946 17191135 96169 9691 5232 HSPA1A HSP70 Hsp70 2 3.5 Increase in Hsp70 protein expression was also found after treatment of cells with 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74947 17191135 96169 9691 5232 HSPA1A HSP70 Hsp70 28 3.5 (SNP), SNP thus suggesting a role for NO in inducing Hsp70 proteins 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74948 17191135 96171 9691 5232 HSPA1A HSP72 Hsp72 2 2.9 Induction of Hsp72 under stress conditions is often accompanied by the induction of 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74949 17191135 96172 9462 5013 HMOX1 HO-1 HO-1 28 6.5 toxicity by acting at three different levels (i) i inducing HO-1 and Hsp72 proteins (ii) ii decreasing the neuronal 3-nitrotyrosine levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74950 17191135 96172 9691 5232 HSPA1A HSP72 Hsp72 30 2.9 acting at three different levels (i) i inducing HO-1 and Hsp72 proteins (ii) ii decreasing the neuronal 3-nitrotyrosine levels and therefore 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74951 17191135 96172 14535 7873 NOS2A NOS NOS 41 2.7 (ii) ii decreasing the neuronal 3-nitrotyrosine levels and therefore inducible NOS activity and (iii) iii by the well known direct free 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000591049358800701<>ScoreDetail__7873|NOS2A|0.000591049358800701__7872|NOS1|0.000524055369725158__ 0 0 0 0 0 74952 17191135 96175 9691 5232 HSPA1A HSP70 Hsp70 6 3.5 During translocation this proteins interact with Hsp70 ATP-dependent binding and the release of Hsp70 provide the major 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74953 17191135 96175 9691 5232 HSPA1A HSP70 Hsp70 13 3.5 proteins interact with Hsp70 ATP-dependent binding and the release of Hsp70 provide the major driving force for complete transport of polypeptides 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74954 17191135 96176 9691 5232 HSPA1A HSP70 Hsp70 8 3.5 Although most imported polypeptides are released from soluble Hsp70 however a subset of aggregation-sensitive polypeptides must be transferred from 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74955 17191135 96176 9691 5232 HSPA1A HSP70 Hsp70 19 3.5 however a subset of aggregation-sensitive polypeptides must be transferred from Hsp70 to Hsp60 for folding 40 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74956 17191135 96176 9718 5261 HSPD1 HSP60 Hsp60 21 1.9 subset of aggregation-sensitive polypeptides must be transferred from Hsp70 to Hsp60 for folding 40 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74957 17191135 96177 9691 5232 HSPA1A HSP70 Hsp70 12 3.5 the close functional interaction between this chaperonin system and the Hsp70 system it is likely that up-regulation of Hsp60 may be 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74958 17191135 96177 9718 5261 HSPD1 HSP60 Hsp60 20 1.9 and the Hsp70 system it is likely that up-regulation of Hsp60 may be a fundamental site targeted by LAC action with 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74959 17191135 96177 11717 6530 LCT LAC LAC 28 0.0 up-regulation of Hsp60 may be a fundamental site targeted by LAC action with consequent restoration of complex IV function under conditions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74960 17191135 96178 9462 5013 HMOX1 HO-1 HO-1 15 6.5 heme oxygenase (HO) HO isoforms were described an inducible isoform HO-1 and a constitutive isoform HO-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74961 17191135 96178 9463 5014 HMOX2 HO-2 HO-2 20 1.9 were described an inducible isoform HO-1 and a constitutive isoform HO-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74962 17191135 96183 9462 5013 HMOX1 HO-1 HO-1 11 6.5 from the identity between the active centers of the enzyme HO-1 and HO-2 broadly differ in cell and tissue regulation and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74963 17191135 96183 9463 5014 HMOX2 HO-2 HO-2 11 1.9 from the identity between the active centers of the enzyme HO-1 and HO-2 broadly differ in cell and tissue regulation and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74964 17191135 96183 9463 5014 HMOX2 HO-2 HO-2 13 1.9 identity between the active centers of the enzyme HO-1 and HO-2 broadly differ in cell and tissue regulation and distribution 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74965 17191135 96184 18723 10261 ROS1 ROS ROS 8 0.6 Heme oxygenase-1 is induced by various stimuli including ROS RNS ischemia heat shock LPS hemin and the neuroprotective agent 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 74966 17191135 96184 6981 22140 FAM20C RNS RNS 9 0.6 Heme oxygenase-1 is induced by various stimuli including ROS RNS ischemia heat shock LPS hemin and the neuroprotective agent Neotrofin 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 74967 17191135 96184 10676 6121 IRF6 LPS LPS 13 0.6 induced by various stimuli including ROS RNS ischemia heat shock LPS hemin and the neuroprotective agent Neotrofin 41 44 -46 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 74968 17191135 96185 9462 5013 HMOX1 HO-1 HO-1 5 6.5 Furthermore in cultured human cells HO-1 expression can be repressed by hypoxia or by the treatment 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74969 17191135 96186 9463 5014 HMOX2 HO-2 HO-2 3 1.9 On the contrary HO-2 the constitutive form is responsive to developmental factors adrenal glucocorticoids 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74970 17191135 96187 9462 5013 HMOX1 HO-1 HO-1 1 6.5 Although HO-1 and HO-2 catalyze the same reaction they play different roles 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74971 17191135 96187 9463 5014 HMOX2 HO-2 HO-2 1 1.9 Although HO-1 and HO-2 catalyze the same reaction they play different roles 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74972 17191135 96187 9463 5014 HMOX2 HO-2 HO-2 3 1.9 Although HO-1 and HO-2 catalyze the same reaction they play different roles in protecting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74973 17191135 96188 9462 5013 HMOX1 HO-1 HO-1 5 6.5 The current hypothesis suggests that HO-1 induction is one of the earlier cellular responses to tissue 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74974 17191135 96189 9463 5014 HMOX2 HO-2 HO-2 3 1.9 On the contrary HO-2 constitutively expressed is primarily involved in maintaining cell heme homeostasis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74975 17191135 96191 9462 5013 HMOX1 HO-1 HO-1 3 6.5 The induction of HO-1 is regulated principally by two upstream enhancers E1 and E2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74976 17191135 96192 12203 6776 MAF MAF Maf 22 0.5 called ARE that also conform to the sequence of the Maf recognition element (MARE) MARE 53 with a consensus sequence (GCnnnGTA) 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74977 17191135 96193 14345 7782 NFE2L2 NRF2 Nrf2 12 2.1 evidence to suggest that heterodimers of NF-E2-related factors 2 (Nrf2) Nrf2 and one or another of the small Maf proteins (i.e 2 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 74978 17191135 96193 12203 6776 MAF MAF Maf 20 0.5 2 (Nrf2) Nrf2 and one or another of the small Maf proteins (i.e i.e MafK MafF and MafG are directly involved 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74979 17191135 96193 12211 6782 MAFK MAFK MafK 23 0.3 one or another of the small Maf proteins (i.e i.e MafK MafF and MafG are directly involved in induction of HO-1 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74980 17191135 96193 12209 6780 MAFF MAFF MafF 24 0.3 or another of the small Maf proteins (i.e i.e MafK MafF and MafG are directly involved in induction of HO-1 gene 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74981 17191135 96193 9462 5013 HMOX1 HO-1 HO-1 33 6.5 MafK MafF and MafG are directly involved in induction of HO-1 gene through these MAREs 53 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74982 17191135 96193 12210 6781 MAFG MAFG MafG 26 0.1 of the small Maf proteins (i.e i.e MafK MafF and MafG are directly involved in induction of HO-1 gene through these 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74983 17191135 96194 14345 7782 NFE2L2 NRF2 Nrf2 5 2.1 A possible model centered on Nrf2 activity suggests that the heme protein Bach1 works as a 2 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 74984 17191135 96194 1778 20473 BRIP1 BACH1 Bach1 12 2.4 model centered on Nrf2 activity suggests that the heme protein Bach1 works as a transcriptional repressor (Fig Fig 1 A B 2 JUMiner_v2.2 1 0 0 2 935 TotalCon:2<>935|BACH1|571|Complete__20473|BRIP1|83990|Complete__<>AvaiableGeneRif=2<>BEST:935|BACH1|0.00105162003880115<>ScoreDetail__935|BACH1|0.00105162003880115__20473|BRIP1|0.000321758489038601__ 0 0 0 0 0 74985 17191135 96195 9462 5013 HMOX1 HO-1 HO-1 3 6.5 Hence regulation of HO-1 gene expression by Bach1 and heme occurs through antagonism between 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74986 17191135 96195 1778 20473 BRIP1 BACH1 Bach1 7 2.4 Hence regulation of HO-1 gene expression by Bach1 and heme occurs through antagonism between transcription activators and the 2 JUMiner_v2.2 1 0 0 2 935 TotalCon:2<>935|BACH1|571|Complete__20473|BRIP1|83990|Complete__<>AvaiableGeneRif=2<>BEST:935|BACH1|0.00105162003880115<>ScoreDetail__935|BACH1|0.00105162003880115__20473|BRIP1|0.000321758489038601__ 0 0 0 0 0 74987 17191135 96195 1778 20473 BRIP1 BACH1 Bach1 19 2.4 heme occurs through antagonism between transcription activators and the repressor Bach1 2 JUMiner_v2.2 1 0 0 2 935 TotalCon:2<>935|BACH1|571|Complete__20473|BRIP1|83990|Complete__<>AvaiableGeneRif=2<>BEST:935|BACH1|0.00105162003880115<>ScoreDetail__935|BACH1|0.00105162003880115__20473|BRIP1|0.000321758489038601__ 0 0 0 0 0 74988 17191135 96196 9462 5013 HMOX1 HO-1 HO-1 6 6.5 Under normal physiological conditions expression of HO-1 is repressed by Bach1/Maf Bach1 Maf complex while increased levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74989 17191135 96196 1778 20473 BRIP1 BACH1 Bach1 10 2.4 normal physiological conditions expression of HO-1 is repressed by Bach1/Maf Bach1 Maf complex while increased levels of heme displace Bach1 from 2 JUMiner_v2.2 1 0 0 2 935 TotalCon:2<>935|BACH1|571|Complete__20473|BRIP1|83990|Complete__<>AvaiableGeneRif=2<>BEST:935|BACH1|0.00105162003880115<>ScoreDetail__935|BACH1|0.00105162003880115__20473|BRIP1|0.000321758489038601__ 0 0 0 0 0 74990 17191135 96196 12203 6776 MAF MAF Maf 10 0.5 physiological conditions expression of HO-1 is repressed by Bach1/Maf Bach1 Maf complex while increased levels of heme displace Bach1 from the 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74991 17191135 96196 1778 20473 BRIP1 BACH1 Bach1 18 2.4 Bach1/Maf Bach1 Maf complex while increased levels of heme displace Bach1 from the enhancers and allow activators such as heterodimer of 2 JUMiner_v2.2 1 0 0 2 935 TotalCon:2<>935|BACH1|571|Complete__20473|BRIP1|83990|Complete__<>AvaiableGeneRif=2<>BEST:935|BACH1|0.00105162003880115<>ScoreDetail__935|BACH1|0.00105162003880115__20473|BRIP1|0.000321758489038601__ 0 0 0 0 0 74992 17191135 96196 12203 6776 MAF MAF Maf 29 0.5 from the enhancers and allow activators such as heterodimer of Maf with NF-E2 related activators (Nrf2), Nrf2 to interact with the 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74993 17191135 96196 14345 7782 NFE2L2 NF-E2 NF-E2 31 1.6 enhancers and allow activators such as heterodimer of Maf with NF-E2 related activators (Nrf2), Nrf2 to interact with the transcriptional promotion 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 14343 7780 NFE2 0 74994 17191135 96196 14345 7782 NFE2L2 NRF2 Nrf2 34 2.1 such as heterodimer of Maf with NF-E2 related activators (Nrf2), Nrf2 to interact with the transcriptional promotion of HO-1 33 2 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 74995 17191135 96196 9462 5013 HMOX1 HO-1 HO-1 42 6.5 activators (Nrf2), Nrf2 to interact with the transcriptional promotion of HO-1 33 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74996 17191135 96197 1681 1062 BLVRA BVR BVR 7 0.9 Heme oxygenase activity is regulated also by BVR because this latter reduces biliverdin (BV), BV the inhibitory product 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74997 17191135 96198 1681 1062 BLVRA BVR BVR 4 0.9 The molecular mass of BVR ranges between 41-42 KDa (human) human and 33-34 KDa (rat), 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74998 17191135 96199 1681 1062 BLVRA BVR BVR 2 0.9 Until now BVR was considered a noninducible protein but recent data showed that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 74999 17191135 96199 10676 6121 IRF6 LPS LPS 19 0.6 recent data showed that the reductase can be induced by LPS and bromobenzene at a post-transcriptional level whereas heat shock has 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 75000 17191135 96200 1681 1062 BLVRA BVR BVR 4 0.9 In the rat brain BVR is co-expressed in cells that display HO-1 and/or and or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75001 17191135 96200 9462 5013 HMOX1 HO-1 HO-1 11 6.5 the rat brain BVR is co-expressed in cells that display HO-1 and/or and or HO-2 under normal conditions as well as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75002 17191135 96200 9463 5014 HMOX2 HO-2 HO-2 13 1.9 is co-expressed in cells that display HO-1 and/or and or HO-2 under normal conditions as well as in regions and cell 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75003 17191135 96200 9462 5013 HMOX1 HO-1 HO-1 33 6.5 cell types that have the potential to express heat shock-inducible HO-1 protein 57 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75004 17191135 96201 1681 1062 BLVRA BVR BVR 4 0.9 Further evidence demonstrated that BVR exhibited developmental changes with the activity increasing after birth and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75005 17191135 96202 1681 1062 BLVRA BVR BVR 9 0.9 Immunohistochemical analysis revealed age-related pattern of the expression of BVR in select rat brain areas such as the cortex substantia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75006 17191135 96203 9463 5014 HMOX2 HO-2 HO-2 16 1.9 abundant in reticuloendothelial organs such as liver and spleen whereas HO-2 is localized in specific organs such as brain kidney and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75007 17191135 96204 9463 5014 HMOX2 HO-2 HO-2 16 1.9 high HO activity under basal conditions mostly accounted for by HO-2 the latter being expressed in neuronal populations in forebrain hippocampus 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75008 17191135 96206 9462 5013 HMOX1 HO-1 HO-1 7 6.5 This finding indicates that the activation of HO-1 and the following formation of CO can be induced by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75009 17191135 96207 4928 2355 CRH CRH CRH 14 0.3 within the parvicellular part of the paraventricular nucleus release both CRH and AVP the neuropeptides that initiate the endocrine response to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75010 17191135 96207 14455 16400 NLRP3 AVP AVP 16 0.3 parvicellular part of the paraventricular nucleus release both CRH and AVP the neuropeptides that initiate the endocrine response to a stressor 1 JUMiner_v2.2 1 0 0 2 894 TotalCon:3<>894|AVP|551|Complete__16400|NLRP3|114548|Complete__5432|IFNAR1|3454|Complete__<>AvaiableGeneRif=3<>BEST:894|AVP|0.000600449511871541<>ScoreDetail__5432|IFNAR1|0.000466924620201651__16400|NLRP3|0.00046775182975843__894|AVP|0.000600449511871541__ 0 0 0 0 0 75011 17191135 96207 16975 9201 POMC ACTH ACTH 32 1.0 endocrine response to a stressor stimulating the release of pituitary ACTH 44 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75012 17191135 96209 9027 4817 HARS2 HO3 HO-3 13 0.8 Maines and her group described a third HO isoform called HO-3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75013 17191135 96211 9027 4817 HARS2 HO3 HO-3 13 0.8 paper Scapagnini et al investigated the regional brain expression of HO-3 and they found that this isoform is expressed mainly in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75014 17191135 96212 9027 4817 HARS2 HO3 HO-3 3 0.8 The regulation of HO-3 gene expression and its synthesis is poorly understood and its 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75015 17191135 96213 23454 12435 TXN TRX Trx 5 2.5 The thioredoxin system The thioredoxin (Trx) Trx system (Trx Trx and Trx reductase has received a considerable 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75016 17191135 96213 23454 12435 TXN TRX Trx 7 2.5 The thioredoxin system The thioredoxin (Trx) Trx system (Trx Trx and Trx reductase has received a considerable attention in the 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75017 17191135 96213 23454 12435 TXN TRX Trx 9 2.5 thioredoxin system The thioredoxin (Trx) Trx system (Trx Trx and Trx reductase has received a considerable attention in the last years 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75018 17191135 96214 23454 12435 TXN TRX Trx 0 2.5 Trx is a ubiquitous thiol oxidoreductase system that regulates cellular redox 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75019 17191135 96215 23454 12435 TXN TRX Trx 19 2.5 a hydrogen donor for ribonucleotide reductase required for DNA synthesis Trx plays an essential role in cell function by limiting oxidative 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75020 17191135 96216 23454 12435 TXN TRX Trx 20 2.5 of many processes is provided by an interaction between the Trx and GSH systems 62 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75021 17191135 96217 23454 12435 TXN TRX Trx 2 2.5 In fact Trx and GSH systems are involved in a variety of redox-dependent 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75022 17191135 96220 23454 12435 TXN TRX Trx 1 2.5 The Trx system rather may play a critical role in the redox 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75023 17191135 96221 23454 12435 TXN TRX Trx 16 2.5 reduced form by TrxR and NADPH collectively known as the Trx system 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75024 17191135 96222 23454 12435 TXN TRX Trx 0 2.5 Trx reductase belongs to the flavoprotein family of pyridine nucleotide disulfide 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75025 17191135 96223 1755 1101 BRCA2 FAD FAD 14 0.3 which each monomer includes two prosthetic flavin adenine dinucleotide (FAD) FAD groups and a NADPH binding site 1 JUMiner_v2.2 1 2 nadph 0 2 3585 TotalCon:3<>1101|BRCA2|675|Complete__3585|FANCD2|2177|Complete__9508|PSEN1|5663|Complete__<>AvaiableGeneRif=3<>BEST:3585|FANCD2|0.000616414966919063<>ScoreDetail__1101|BRCA2|0.000291740765865872__9508|PSEN1|0.000550124664860037__3585|FANCD2|0.000616414966919063__ 0 0 0 0 0 75026 17191135 96224 1755 1101 BRCA2 FAD FAD 18 0.3 consisting of two cysteines adjacent to the flavin ring of FAD in the N-terminal part of the protein 1 JUMiner_v2.2 1 2 nadph 0 2 3585 TotalCon:3<>1101|BRCA2|675|Complete__3585|FANCD2|2177|Complete__9508|PSEN1|5663|Complete__<>AvaiableGeneRif=3<>BEST:3585|FANCD2|0.000616414966919063<>ScoreDetail__1101|BRCA2|0.000291740765865872__9508|PSEN1|0.000550124664860037__3585|FANCD2|0.000616414966919063__ 0 0 0 0 0 75027 17191135 96226 23454 12435 TXN TRX Trx 18 2.5 the catalytic activity of mammalian TrxR toward reduction of oxidized Trx and various antioxidant molecules such as lipoic acid ascorbic acid 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75028 17191135 96234 23454 12435 TXN TRX Trx 0 2.5 Trx which behaves as a soluble protein after disruption of cells 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75029 17191135 96234 23454 12435 TXN TRX1 Trx-1 18 3.0 of cells exists as one of the cytoplasmic proteins (Trx-1) Trx-1 and a mitochondrial (Trx-2) Trx-2 isoform 60 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75030 17191135 96234 23455 17772 TXN2 TRX2 Trx-2 22 1.3 of the cytoplasmic proteins (Trx-1) Trx-1 and a mitochondrial (Trx-2) Trx-2 isoform 60 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75031 17191135 96235 23454 12435 TXN TRX1 Trx-1 10 3.0 A growing number of studies report a striking association between Trx-1 up-regulation in the CNS and neuron survival following various injuries 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75032 17191135 96236 23454 12435 TXN TRX1 Trx-1 0 3.0 Trx-1 and TrxR the most extensively studied eukaryotic thioredoxin proteins were 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75033 17191135 96237 23454 12435 TXN TRX1 Trx-1 0 3.0 Trx-1 has been then found widely expressed in rat brain especially 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75034 17191135 96238 23454 12435 TXN TRX1 Trx-1 3 3.0 Immunohistochemical analysis of Trx-1 in human brain showed positive Trx1-like staining in white matter 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75035 17191135 96239 23454 12435 TXN TRX Trx 4 2.5 The promoter of the Trx gene contains a series of stress-responsive elements various transcription factor 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75036 17191135 96239 21038 11205 SP1 SP1 SP1 19 0.6 of stress-responsive elements various transcription factor binding sites such as SP1 GCF and WT-ZFP conferring constitutive expression inducible expression elements such 1 JUMiner_v2.2 1 0 0 2 11205 TotalCon:3<>11205|SP1|6667|Complete__26780|DAND5|199699|No_GeneRif__9514|PSG1|5669|Complete__<>AvaiableGeneRif=2<>BEST:11205|SP1|0.000794334123436801<>ScoreDetail__9514|PSG1|0.000307536098880178__11205|SP1|0.000794334123436801__ 0 0 0 0 0 75037 17191135 96239 2057 1317 C2orf3 GCF GCF 20 0.3 stress-responsive elements various transcription factor binding sites such as SP1 GCF and WT-ZFP conferring constitutive expression inducible expression elements such as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75038 17191135 96239 10824 6204 JUN AP-1 AP-1 31 1.6 and WT-ZFP conferring constitutive expression inducible expression elements such as AP-1 AP-2 NF-kB Oct-1 PEA-3 Myb and the antioxidant-responsive element (ARE) 1 JUMiner_v2.2 1 0 0 2 6204 TotalCon:5<>3796|FOS|2353|Complete__3797|FOSB|2354|Complete__6204|JUN|3725|Complete__6205|JUNB|3726|Complete__6206|JUND|3727|Complete__<>AvaiableGeneRif=5<>BEST:6204|JUN|0.00077545260429419<>ScoreDetail__3796|FOS|0.000631914674627876__3797|FOSB|0.000554782843078888__6205|JUNB|0.00063223039517478__6204|JUN|0.00077545260429419__6206|JUND|0.00070916977257676__ 0 0 0 0 0 75039 17191135 96239 22027 11742 TFAP2A AP-2 AP-2 32 1.6 WT-ZFP conferring constitutive expression inducible expression elements such as AP-1 AP-2 NF-kB Oct-1 PEA-3 Myb and the antioxidant-responsive element (ARE) ARE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75040 17191135 96239 14352 7794 NFKB1 NF-kB NF-kB 33 0.6 conferring constitutive expression inducible expression elements such as AP-1 AP-2 NF-kB Oct-1 PEA-3 Myb and the antioxidant-responsive element (ARE) ARE 71 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75041 17191135 96239 20185 10963 SLC22A1 OCT1 Oct-1 34 0.3 constitutive expression inducible expression elements such as AP-1 AP-2 NF-kB Oct-1 PEA-3 Myb and the antioxidant-responsive element (ARE) ARE 71 11 JUMiner_v2.2 1 0 0 2 9212 TotalCon:2<>9212|POU2F1|5451|Complete__10963|SLC22A1|6580|Complete__<>AvaiableGeneRif=2<>BEST:9212|POU2F1|0.000801597851717757<>ScoreDetail__10963|SLC22A1|0.000501457087467555__9212|POU2F1|0.000801597851717757__ 0 0 0 0 0 75042 17191135 96239 6818 3493 ETV4 PEA3 PEA-3 35 0.3 expression inducible expression elements such as AP-1 AP-2 NF-kB Oct-1 PEA-3 Myb and the antioxidant-responsive element (ARE) ARE 71 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75043 17191135 96239 13916 7545 MYB MYB Myb 36 0.3 inducible expression elements such as AP-1 AP-2 NF-kB Oct-1 PEA-3 Myb and the antioxidant-responsive element (ARE) ARE 71 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75044 17191135 96240 23454 12435 TXN TRX1 Trx-1 1 3.0 ARE-mediated Trx-1 induction involves the transcription factor Nfr2 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75045 17191135 96241 23454 12435 TXN TRX Trx 6 2.5 Moreover it has been reported that Trx is constitutively present as a surface-associated sulfhydryl protein in plasma 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75046 17191135 96242 23454 12435 TXN TRX Trx 14 2.5 UV irradiation and hydrogen peroxide have been shown to induce Trx expression and secretion as a redox-sensitive molecule with cytokine-like and 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75047 17191135 96243 23454 12435 TXN TRX Trx 31 2.5 and hemin has been reported to cause the translocation of Trx from the cytoplasm to the nucleus where it regulates the 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75048 17191135 96243 10824 6204 JUN AP-1 AP-1 54 1.6 DNA binding activity of critical transcription factors such as the AP-1 family members NF-kB Jun Fos p53 CREB PEBP2/CBF, PEBP2 CBF 1 JUMiner_v2.2 1 0 0 2 6204 TotalCon:5<>3796|FOS|2353|Complete__3797|FOSB|2354|Complete__6204|JUN|3725|Complete__6205|JUNB|3726|Complete__6206|JUND|3727|Complete__<>AvaiableGeneRif=5<>BEST:6204|JUN|0.00077545260429419<>ScoreDetail__3796|FOS|0.000631914674627876__3797|FOSB|0.000554782843078888__6205|JUNB|0.00063223039517478__6204|JUN|0.00077545260429419__6206|JUND|0.00070916977257676__ 0 0 0 0 0 75049 17191135 96243 14352 7794 NFKB1 NF-kB NF-kB 57 0.6 of critical transcription factors such as the AP-1 family members NF-kB Jun Fos p53 CREB PEBP2/CBF, PEBP2 CBF Myb all involved 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75050 17191135 96243 7683 3796 FOS FOS Fos 59 1.8 transcription factors such as the AP-1 family members NF-kB Jun Fos p53 CREB PEBP2/CBF, PEBP2 CBF Myb all involved in fundamental 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75051 17191135 96243 22671 11998 TP53 p53 p53 60 0.6 factors such as the AP-1 family members NF-kB Jun Fos p53 CREB PEBP2/CBF, PEBP2 CBF Myb all involved in fundamental processes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75052 17191135 96243 4911 2345 CREB1 CREB CREB 61 1.9 such as the AP-1 family members NF-kB Jun Fos p53 CREB PEBP2/CBF, PEBP2 CBF Myb all involved in fundamental processes such 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75053 17191135 96243 13916 7545 MYB MYB Myb 63 0.1 family members NF-kB Jun Fos p53 CREB PEBP2/CBF, PEBP2 CBF Myb all involved in fundamental processes such as gene expression cell 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75054 17191135 96244 23454 12435 TXN TRX Trx 3 2.5 Plasma levels of Trx in normal individuals vary between 10 and 80 ng/ml; ng 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75055 17191135 96245 23454 12435 TXN TRX1 Trx-1 6 3.0 Of note several studies reported increased Trx-1 expression in many human primary cancers and tumor cell lines 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75056 17191135 96246 23454 12435 TXN TRX Trx 1 2.5 Elevated Trx levels may contribute to increased cancer cell proliferation and resistance 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75057 17191135 96247 23454 12435 TXN TRX1 Trx-1 4 3.0 Recent work suggests that Trx-1 play a key role in NGF signaling pathways 74 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75058 17191135 96247 14373 7808 NGF NGF NGF 10 0.6 Recent work suggests that Trx-1 play a key role in NGF signaling pathways 74 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75059 17191135 96248 14373 7808 NGF NGF NGF 0 0.6 NGF a neurotrophic factor regulating development maintenance and function of the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75060 17191135 96248 23454 12435 TXN TRX1 Trx-1 17 3.0 and function of the CNS has been shown to activate Trx-1 expression via cyclic AMP (cAMP)-response cAMP -response elements (CREs) CREs 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75061 17191135 96248 23454 12435 TXN TRX1 Trx-1 28 3.0 AMP (cAMP)-response cAMP -response elements (CREs) CREs present in the Trx-1 gene promoter and also to induce nuclear translocation of Trx1 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75062 17191135 96248 23454 12435 TXN TRX1 Trx1 38 2.5 Trx-1 gene promoter and also to induce nuclear translocation of Trx1 75 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75063 17191135 96249 23454 12435 TXN TRX Trx 17 2.5 to regulate the function of proteins through thiol-disulfide exchange reactions Trx may also have beneficial effects during oxidative stress by transcriptionally 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75064 17191135 96249 9462 5013 HMOX1 HO-1 HO-1 29 6.5 also have beneficial effects during oxidative stress by transcriptionally upregulating HO-1 with important cytoprotective pleiotropic effects deriving from heme degradation biliverdin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75065 17191135 96251 23454 12435 TXN TRX Trx 9 2.5 Besides the role as a source of reducing equivalents Trx by itself acts as antioxidant or ROS scavenger 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75066 17191135 96251 18723 10261 ROS1 ROS ROS 16 0.6 of reducing equivalents Trx by itself acts as antioxidant or ROS scavenger 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 75067 17191135 96252 23454 12435 TXN TRX Trx 2 2.5 In fact Trx eliminates singlet oxygen hydroxyl radical and hydrogen peroxide 78 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75068 17191135 96253 23454 12435 TXN TRX Trx 8 2.5 Another family of proteins acting in conjunction with Trx is the peroxide scavenger Peroxiredoxin (Prx) Prx 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75069 17191135 96253 17269 16753 PRDX6 PRX Prx 14 0.3 in conjunction with Trx is the peroxide scavenger Peroxiredoxin (Prx) Prx 2 JUMiner_v2.2 1 0 0 2 16753 TotalCon:2<>13797|PRX|57716|Complete__16753|PRDX6|9588|Complete__<>AvaiableGeneRif=2<>BEST:16753|PRDX6|0.000904407642412684<>ScoreDetail__16753|PRDX6|0.000904407642412684__13797|PRX|0.00074121081355502__ 0 0 0 0 0 75070 17191135 96254 23454 12435 TXN TRX Trx 23 2.5 antioxidant enzymes most of which use the reducing activity of Trx or other electron donors to catalyze the reduction of peroxides 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75071 17191135 96255 17269 16753 PRDX6 PRX Prx 8 0.3 A number of studies have shown that several Prx isoforms can be induced in brain in response to various 2 JUMiner_v2.2 1 0 0 2 16753 TotalCon:2<>13797|PRX|57716|Complete__16753|PRDX6|9588|Complete__<>AvaiableGeneRif=2<>BEST:16753|PRDX6|0.000904407642412684<>ScoreDetail__16753|PRDX6|0.000904407642412684__13797|PRX|0.00074121081355502__ 0 0 0 0 0 75072 17191135 96256 23454 12435 TXN TRX Trx 3 2.5 As for cytosolic Trx (Trx-1), Trx-1 the induction of Prx-1 appears to involve the 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75073 17191135 96256 23454 12435 TXN TRX1 Trx-1 4 3.0 As for cytosolic Trx (Trx-1), Trx-1 the induction of Prx-1 appears to involve the transcription factor 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75074 17191135 96256 17263 9352 PRDX1 PRX1 Prx-1 8 0.3 As for cytosolic Trx (Trx-1), Trx-1 the induction of Prx-1 appears to involve the transcription factor Nrf2 11 JUMiner_v2.2 1 0 0 2 9142 TotalCon:2<>9352|PRDX1|5052|Complete__9142|PRRX1|5396|Complete__<>AvaiableGeneRif=2<>BEST:9142|PRRX1|0.000865361317195306<>ScoreDetail__9352|PRDX1|0.000802147728292869__9142|PRRX1|0.000865361317195306__ 0 0 0 0 0 75075 17191135 96256 14345 7782 NFE2L2 NRF2 Nrf2 15 2.1 the induction of Prx-1 appears to involve the transcription factor Nrf2 2 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 75076 17191135 96257 17269 16753 PRDX6 PRX Prx 7 0.3 Recent studies have revealed aberrant patterns of Prx expression in the CNS of patients affected by neurodegenerative disorders 2 JUMiner_v2.2 1 0 0 2 16753 TotalCon:2<>13797|PRX|57716|Complete__16753|PRDX6|9588|Complete__<>AvaiableGeneRif=2<>BEST:16753|PRDX6|0.000904407642412684<>ScoreDetail__16753|PRDX6|0.000904407642412684__13797|PRX|0.00074121081355502__ 0 0 0 0 0 75077 17191135 96258 23454 12435 TXN TRX Trx 4 2.5 A second slightly larger Trx isoform (Trx-2), Trx-2 is also present in mammalian cells where 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75078 17191135 96258 23455 17772 TXN2 TRX2 Trx-2 6 1.3 A second slightly larger Trx isoform (Trx-2), Trx-2 is also present in mammalian cells where exhibits characteristics consistent 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75079 17191135 96259 23455 17772 TXN2 TRX2 Trx-2 0 1.3 Trx-2 inactivation studies in DT-40 chicken cells suggest that this mitochondrial 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75080 17191135 96259 23454 12435 TXN TRX Trx 11 2.5 inactivation studies in DT-40 chicken cells suggest that this mitochondrial Trx isoenzyme is essential for cell survival 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75081 17191135 96260 23455 17772 TXN2 TRX2 Trx-2 4 1.3 The homozygous disruption of Trx-2 generates a lethal embryonic phenotype in mice 81 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75082 17191135 96261 23455 17772 TXN2 TRX2 Trx-2 3 1.3 In support of Trx-2 protective function(s) function s against oxidative stress transfection of Trx2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75083 17191135 96261 23455 17772 TXN2 TRX2 Trx2 11 1.3 Trx-2 protective function(s) function s against oxidative stress transfection of Trx2 reduced the sensitivity of human osteosarcoma and embryo kidney cells 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75084 17191135 96261 22000 11730 TERT TERT tert 29 0.3 embryo kidney cells to cell death induced by etopoxide or tert -butylhydroperoxide 82 14 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 75085 17191135 96262 23455 17772 TXN2 TRX2 Trx2 2 1.3 Mitochondrial isoform Trx2 is abundant and widely distributed in rat brain 83 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75086 17191135 96263 23455 17772 TXN2 TRX2 Trx-2 6 1.3 Brain regions showing highest expression of Trx-2 at the RNA and protein levels include the olfactory bulb 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75087 17191135 96264 23455 17772 TXN2 TRX2 Trx2 4 1.3 The expression pattern of Trx2 appears to be associated with brain regions producing high levels 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75088 17191135 96264 18723 10261 ROS1 ROS ROS 16 0.6 to be associated with brain regions producing high levels of ROS 83 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 75089 17191135 96266 926 620 APP amyloid amyloid 7 1.3 It is characterized pathologically by deposition of amyloid B-peptide (AB) AB in senile (neuritic) neuritic plaques and the 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 75090 17191135 96269 12369 6893 MAPT tau tau 42 1.8 ubiquitination clearing misfolded proteins to the proteasome and segregation of tau aggregates from the cellular machinery and recruitment of chaperone pairs 1 JUMiner_v2.2 1 2 35 0 0 0 0 0 0 0 0 75091 17191135 96269 9691 5232 HSPA1A HSP70 Hsp70 54 3.5 from the cellular machinery and recruitment of chaperone pairs including Hsp70 and Hsp27 endowed with anti-apoptotic properties 85 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75092 17191135 96269 9708 5247 HSPB2 HSP27 Hsp27 56 1.9 cellular machinery and recruitment of chaperone pairs including Hsp70 and Hsp27 endowed with anti-apoptotic properties 85 2 JUMiner_v2.2 1 0 0 2 5246 TotalCon:2<>5246|HSPB1|3315|Complete__5247|HSPB2|3316|Complete__<>AvaiableGeneRif=2<>BEST:5246|HSPB1|0.000908602424758586<>ScoreDetail__5246|HSPB1|0.000908602424758586__5247|HSPB2|0.000783297072361479__ 0 0 0 0 0 75093 17191135 96270 12369 6893 MAPT tau tau 3 1.8 Binding of phosphorylated tau to Hsp70 implies that the complex may be a substrate 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75094 17191135 96270 9691 5232 HSPA1A HSP70 Hsp70 5 3.5 Binding of phosphorylated tau to Hsp70 implies that the complex may be a substrate for the 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75095 17191135 96270 7962 4012 FUT1 HSC Hsc 23 0.5 for the E3 ligase carboxyl terminus of heat-shock cognate (Hsc)70-interacting Hsc 70-interacting protein (CHIP) CHIP 86 -88 2 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 75096 17191135 96270 21493 11427 STUB1 CHIP CHIP 25 1.6 carboxyl terminus of heat-shock cognate (Hsc)70-interacting Hsc 70-interacting protein (CHIP) CHIP 86 -88 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75097 17191135 96272 9691 5232 HSPA1A HSP70 Hsp70 2 3.5 Together with Hsp70 CHIP can regulate tau ubiquitination and degradation in a cell 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75098 17191135 96272 21493 11427 STUB1 CHIP CHIP 3 1.6 Together with Hsp70 CHIP can regulate tau ubiquitination and degradation in a cell culture 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75099 17191135 96272 12369 6893 MAPT tau tau 6 1.8 Together with Hsp70 CHIP can regulate tau ubiquitination and degradation in a cell culture system 87 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75100 17191135 96273 21493 11427 STUB1 CHIP CHIP 3 1.6 Increased levels of CHIP and Hsp70 has ben detected in AD compared with normal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75101 17191135 96273 9691 5232 HSPA1A HSP70 Hsp70 5 3.5 Increased levels of CHIP and Hsp70 has ben detected in AD compared with normal controls 86 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75102 17191135 96274 21493 11427 STUB1 CHIP CHIP 7 1.6 In a JNPL3 mouse brain tauopathy model CHIP was widely distributed but weakly expressed in spinal cord which 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75103 17191135 96274 12369 6893 MAPT tau tau 24 1.8 in spinal cord which was the most prominent region for tau inclusions and neuronal loss 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75104 17191135 96275 21493 11427 STUB1 CHIP CHIP 3 1.6 Protein levels of CHIP in cerebellar regions (a a brain region highly resistant to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75105 17191135 96276 21493 11427 STUB1 CHIP CHIP 6 1.6 These findings suggest that increases in CHIP may protect against the formation of neurofibrillary tangles the major 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75106 17191135 96278 926 620 APP amyloid amyloid 26 1.3 intracellular immunoreactive deposits as well as the formation of intracellular amyloid 89 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 75107 17191135 96279 9691 5232 HSPA1A HSP70 Hsp70 16 3.5 specifically coimmunoprecipitate with AB has identified chaperone proteins such as Hsp70 and alpha B-crystallin-related small Hsp (Hsp16) Hsp16 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75108 17191135 96279 9691 5232 HSPA1A HSP Hsp 21 1.9 identified chaperone proteins such as Hsp70 and alpha B-crystallin-related small Hsp (Hsp16) Hsp16 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75109 17191135 96281 9462 5013 HMOX1 HO-1 HO-1 4 6.5 Recently the involvement of HO-1 in the antidegenerative mechanisms operating in AD has received considerable 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75110 17191135 96281 926 620 APP amyloid amyloid 23 1.3 received considerable attention as it has been demonstrated that the amyloid precursor protein (APP) APP decreases HO activity thus reducing the 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 75111 17191135 96281 926 620 APP APP APP 26 0.3 it has been demonstrated that the amyloid precursor protein (APP) APP decreases HO activity thus reducing the intracellular levels of bilirubin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75112 17191135 96282 9462 5013 HMOX1 HO-1 HO-1 0 6.5 HO-1 induction which occurs together with the induction of other stress 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75113 17191135 96283 9462 5013 HMOX1 HO-1 HO-1 6 6.5 Significant increases in the levels of HO-1 have been observed in AD brains in association with neurofibrillary 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75114 17191135 96283 9462 5013 HMOX1 HO-1 HO-1 20 6.5 in AD brains in association with neurofibrillary tangles and also HO-1 mRNA was found increased in AD neocortex and cerebral vessels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75115 17191135 96284 9462 5013 HMOX1 HO-1 HO-1 0 6.5 HO-1 increase was not only in association with neurofibrillary tangles but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75116 17191135 96285 9462 5013 HMOX1 HO-1 HO-1 9 6.5 In addition Takeda et al explored the relationship between HO-1 and tau protein this latter being the major component of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75117 17191135 96285 12369 6893 MAPT tau tau 11 1.8 addition Takeda et al explored the relationship between HO-1 and tau protein this latter being the major component of intraneuronal neurofibrillary 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75118 17191135 96286 9462 5013 HMOX1 HO-1 HO-1 5 6.5 In transfected neuroblastoma cells overexpressing HO-1 the activity of this enzyme was increased and conversely the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75119 17191135 96286 12369 6893 MAPT tau tau 18 1.8 of this enzyme was increased and conversely the level of tau protein was significantly decreased when compared with antisense HO-1 or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75120 17191135 96286 9462 5013 HMOX1 HO-1 HO-1 27 6.5 of tau protein was significantly decreased when compared with antisense HO-1 or vector transfected cells 93 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75121 17191135 96287 12369 6893 MAPT tau tau 3 1.8 The suppression of tau protein expression was almost completely counteracted by zinc-deuteroporphyrin a specific 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75122 17191135 96288 9462 5013 HMOX1 HO-1 HO-1 14 6.5 (extracellular extracellular signal-regulated kinases were also decreased in cells overexpressing HO-1 although no changes in the expression of total ERKs were 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75123 17191135 96288 12337 6871 MAPK1 ERK ERKs 4 0.0 The activated forms of ERKs (extracellular extracellular signal-regulated kinases were also decreased in cells overexpressing 13 JUMiner_v2.2 1 1 UserEdit 0 2 6871 TotalCon:2<>3393|EPHB2|2048|Complete__6871|MAPK1|5594|Complete__<>AvaiableGeneRif=2<>BEST:6871|MAPK1|0.000741317599596616<>ScoreDetail__3393|EPHB2|0.000491692575393669__6871|MAPK1|0.000741317599596616__ 1 1 6697 3393 EPHB2 1 extracellular signal-regulated kinase 75124 17191135 96288 12337 6871 MAPK1 ERK ERKs 23 0.0 overexpressing HO-1 although no changes in the expression of total ERKs were observed 93 13 JUMiner_v2.2 1 1 UserEdit 0 2 6871 TotalCon:2<>3393|EPHB2|2048|Complete__6871|MAPK1|5594|Complete__<>AvaiableGeneRif=2<>BEST:6871|MAPK1|0.000741317599596616<>ScoreDetail__3393|EPHB2|0.000491692575393669__6871|MAPK1|0.000741317599596616__ 1 1 6697 3393 EPHB2 1 extracellular signal-regulated kinase 75125 17191135 96290 23454 12435 TXN TRX Trx 10 2.5 Among the very few studies available on the expression of Trx cycle enzymes in neurodegenerative processes one report indicated increased Trx1 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75126 17191135 96290 23454 12435 TXN TRX1 Trx1 20 2.5 Trx cycle enzymes in neurodegenerative processes one report indicated increased Trx1 protein and RNA levels in the grey and white matter 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75127 17191135 96291 9462 5013 HMOX1 HO-1 HO-1 26 6.5 AD patients of a significant increase in the expression of HO-1 and TRXr whereas this latter was not increased in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75128 17191135 96294 9462 5013 HMOX1 HO-1 HO-1 13 6.5 lymphocytes showed an increased expression of inducible nitric oxide synthase HO-1 Hsp72 Hsp60 and TrxR 96 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75129 17191135 96294 9691 5232 HSPA1A HSP72 Hsp72 14 2.9 showed an increased expression of inducible nitric oxide synthase HO-1 Hsp72 Hsp60 and TrxR 96 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75130 17191135 96294 9718 5261 HSPD1 HSP60 Hsp60 15 1.9 an increased expression of inducible nitric oxide synthase HO-1 Hsp72 Hsp60 and TrxR 96 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75131 17191135 96295 23454 12435 TXN TRX Trx 13 2.5 that treatments of primary rat hippocampal cell cultures with exogenous Trx enhanced their survival against B-amyloid cytotoxicity 97 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75132 17191135 96296 23454 12435 TXN TRX Trx 6 2.5 Thus it has been suggested that Trx might play a protective role in AD and Trx-1 deficit 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75133 17191135 96296 23454 12435 TXN TRX1 Trx-1 15 3.0 that Trx might play a protective role in AD and Trx-1 deficit might eventually contribute to increased oxidative stress and subsequent 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75134 17191135 96297 23454 12435 TXN TRX1 Trx-1 4 3.0 In contrast to low Trx-1 protein levels TrxR activity was significantly elevated in the amygdala 11 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>7132|MLL|4297|Complete__12435|TXN|7295|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.000910069932883855<>ScoreDetail__12435|TXN|0.000910069932883855__7132|MLL|0.000511425008070683__ 0 0 0 0 0 75135 17191135 96298 20996 11179 SOD1 SOD1 SOD1 17 1.9 antioxidant enzymatic activities such as GPx GSSG reductase CAT and SOD1 were also found elevated in several regions of AD brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75136 17191135 96298 3544 1516 CAT CAT CAT 15 0.1 other main antioxidant enzymatic activities such as GPx GSSG reductase CAT and SOD1 were also found elevated in several regions of 6 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>1516|CAT|847|Complete__13734|GLYAT|10249|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 75137 17191135 96300 23454 12435 TXN TRX Trx 8 2.5 It is likely that the expression of the Trx cycle enzymes must be tightly regulated in order to maintain 2 JUMiner_v2.2 1 0 0 2 12435 TotalCon:2<>12435|TXN|7295|Complete__25507|VAC14|55697|Complete__<>AvaiableGeneRif=2<>BEST:12435|TXN|0.00116607298420909<>ScoreDetail__12435|TXN|0.00116607298420909__25507|VAC14|0.000609444422600558__ 0 0 0 0 0 75138 17191135 96302 9462 5013 HMOX1 HO-1 HO-1 5 6.5 The protective role played by HO-1 in AD in fact raises new possibilities regarding the use 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75139 17191135 96302 9462 5013 HMOX1 HO-1 HO-1 24 6.5 the use of natural substances which are able to increase HO-1 levels as potential drugs for the treatment of AD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75140 17191135 96305 18723 10261 ROS1 ROS ROS 16 0.6 to inhibit lipid peroxidation and to effectively intercept and neutralize ROS and RNS 23 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 75141 17191135 96305 6981 22140 FAM20C RNS RNS 18 0.6 lipid peroxidation and to effectively intercept and neutralize ROS and RNS 23 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 75142 17191135 96306 9462 5013 HMOX1 HO-1 HO-1 9 6.5 In addition curcumin has been shown to significantly increase HO-1 in astrocytes and vascular endothelial cells 100 101 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75143 17191135 96307 9462 5013 HMOX1 HO-1 HO-1 4 6.5 This latter effect on HO-1 can explain at least in part the strong antioxidant properties 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75144 17191135 96307 18723 10261 ROS1 ROS ROS 32 0.6 that HO-1-derived BR has the ability to efficiently scavenge both ROS and RNS 8 11 -13 99 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 75145 17191135 96307 6981 22140 FAM20C RNS RNS 34 0.6 BR has the ability to efficiently scavenge both ROS and RNS 8 11 -13 99 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 75146 17191135 96309 16343 17468 PDLIM5 LIM Lim 4 0.3 Based on these findings Lim and colleagues have provided convincing evidence that dietary curcumin given 2 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 75147 17191135 96314 11717 6530 LCT LAC LAC 3 0.0 Acetyl-l -carnitine (LAC), LAC is a compound of great interest for its wide clinical 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75148 17191135 96322 9691 5232 HSPA1A HSP72 hsp72 40 2.9 modulates specific genes in the rat CNS such as the hsp72 gene the gene for the isoform of 14-3-3 protein and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75149 17191135 96322 11717 6530 LCT LAC LAC 29 0.0 often obscured by more abundant ones it has reported that LAC modulates specific genes in the rat CNS such as the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75150 17191135 96324 9718 5261 HSPD1 HSP60 Hsp60 14 1.9 for the first time that acetylcarnitine induces heme oxygenase-1 and Hsp60 heat-shock proteins with a mechanism involving activation and nuclear translocation 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75151 17191135 96324 14345 7782 NFE2L2 NRF2 Nrf2 29 2.1 mechanism involving activation and nuclear translocation of the transcription factor Nrf2 27 2 JUMiner_v2.2 1 0 0 2 7782 TotalCon:2<>7782|NFE2L2|4780|Complete__4071|GABPA|2551|Complete__<>AvaiableGeneRif=2<>BEST:7782|NFE2L2|0.00155191154741079<>ScoreDetail__7782|NFE2L2|0.00155191154741079__4071|GABPA|0.000525009545628102__ 0 0 0 0 0 75152 17191135 96326 9462 5013 HMOX1 HO-1 HO-1 29 6.5 modulate ARE-mediated expression of stress-inducible genes 107 -124 such as HO-1 G-glutamylcysteine synthetase Mn-SOD and glutathione S-transferase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75153 17191135 96326 20997 11180 SOD2 Mn-SOD Mn-SOD 32 1.9 of stress-inducible genes 107 -124 such as HO-1 G-glutamylcysteine synthetase Mn-SOD and glutathione S-transferase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 75154 17191135 96329 20996 11179 SOD1 ALS ALS 7 1.9 Protein conformational diseases such as AD PD ALS HD and MS affect a large portion of our aging 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000570340949044605<>ScoreDetail__5468|IGFALS|0.000429859285933318__11179|SOD1|0.000570340949044605__ 0 0 0 0 0 75155 17191135 96334 18723 10261 ROS1 ROS ROS 24 0.6 (mal)folding mal folding cycles and oxidative damage cycles sustaining excessive ROS production and oxidative stress 125 126 (Figs Figs 3 4 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 75156 17191135 96335 18723 10261 ROS1 ROS ROS 1 0.6 These ROS set in motion a lot of redox reactions which can 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 75157 17191135 96336 18723 10261 ROS1 ROS ROS 8 0.6 The ability of a cell to deal with ROS and oxidative stress requires functional chaperones antioxidant production protein degradation 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 75158 17191135 96337 18723 10261 ROS1 ROS ROS 20 0.6 susceptible to perturbations in the quality control system and that ROS play an important role in the development and/or and or 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 75159 17191135 96339 926 620 APP amyloid amyloid 12 1.3 s quality control system becomes overwhelmed conformational changes occur to amyloid polypeptide intermediates generating stable oligomers with an anti-parallel crossed B-pleated 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 75160 17191135 96341 926 620 APP amyloid amyloid 8 1.3 Although it is clear why mutant proteins form amyloid it is harder to rationalize why a wild-type protein adopts 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 75161 17191135 96342 926 620 APP amyloid amyloid 11 1.3 discrepancy suggests that another event likely triggers misfolding in sporadic amyloid disease 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 75162 17191135 96349 18723 10261 ROS1 ROS ROS 24 0.6 the altered membrane permeability results in Ca 2 leakage and ROS formation 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 75163 17191135 96351 18723 10261 ROS1 ROS ROS 0 0.6 ROS generated during and as a consequence of protein misfolding cause 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 75164 17191135 96352 18723 10261 ROS1 ROS ROS-induced 10 0.3 In these conditions chaperone proteins themselves can be target of ROS-induced alterations 1 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 75165 17191135 96354 9462 5013 HMOX1 HO-1 HO-1 13 6.5 phenolic compounds such as curcumin and ferulic acid can induce HO-1 and TRXr and thus reduce AD strongly indicates the therapeutic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 76076 17214440 97706 20996 11179 SOD1 ALS ALS 6 1.7 In most cases the cause of ALS is unknown although in a number of familial ALS cases 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014093227737752<>ScoreDetail__5468|IGFALS|0.000540686672073533__11179|SOD1|0.0014093227737752__ 0 0 0 0 0 76077 17214440 97706 20996 11179 SOD1 ALS ALS 15 1.7 of ALS is unknown although in a number of familial ALS cases mutations in the superoxide dismutase 1 (SOD1) SOD1 gene 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014093227737752<>ScoreDetail__5468|IGFALS|0.000540686672073533__11179|SOD1|0.0014093227737752__ 0 0 0 0 0 76078 17214440 97706 20996 11179 SOD1 SOD1 SOD1 23 1.7 familial ALS cases mutations in the superoxide dismutase 1 (SOD1) SOD1 gene were discovered 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 76079 17214440 97711 20996 11179 SOD1 ALS ALS 10 1.7 Despite the fact that only the motor neurons die during ALS it is clear that also other cell types play an 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014093227737752<>ScoreDetail__5468|IGFALS|0.000540686672073533__11179|SOD1|0.0014093227737752__ 0 0 0 0 0 76080 17214440 97714 20996 11179 SOD1 ALS ALS 31 1.7 disease and on the survival of a mouse model for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014093227737752<>ScoreDetail__5468|IGFALS|0.000540686672073533__11179|SOD1|0.0014093227737752__ 0 0 0 0 0 76081 17214440 97716 20996 11179 SOD1 ALS ALS 20 1.7 the mechanisms responsible for the selective motor neuron death during ALS and we hope that this information can help in the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014093227737752<>ScoreDetail__5468|IGFALS|0.000540686672073533__11179|SOD1|0.0014093227737752__ 0 0 0 0 0 76082 17214440 97716 20996 11179 SOD1 ALS ALS 48 1.7 incurable disease 3000 Leuven motorneurondood bij Amyotrofische Lateraal Sclerose (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.0014093227737752<>ScoreDetail__5468|IGFALS|0.000540686672073533__11179|SOD1|0.0014093227737752__ 0 0 0 0 0 76739 17241118 98803 4645 2160 CNR2 CB2 CB2 1 0.9 The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 76740 17241118 98804 20996 11179 SOD1 ALS ALS 3 1.7 Amyotrophic lateral sclerosis (ALS) ALS is a neurodegenerative disease characterized by progressive motor neuron loss 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00113214309859518<>ScoreDetail__5468|IGFALS|0.00054973582139694__11179|SOD1|0.00113214309859518__ 0 0 0 0 0 76741 17241118 98806 20996 11179 SOD1 ALS ALS 6 1.7 Neuroinflammation may accelerate the progression of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00113214309859518<>ScoreDetail__5468|IGFALS|0.00054973582139694__11179|SOD1|0.00113214309859518__ 0 0 0 0 0 76742 17241118 98807 4644 2159 CNR1 CB1 CB1 8 0.9 Cannabinoids produce anti-inflammatory actions via cannabinoid receptor 1 (CB1) CB1 and cannabinoid receptor 2 (CB2), CB2 and delay the progression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 76743 17241118 98807 4645 2160 CNR2 CB2 CB2 13 0.9 cannabinoid receptor 1 (CB1) CB1 and cannabinoid receptor 2 (CB2), CB2 and delay the progression of neuroinflammatory diseases 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 76744 17241118 98808 4645 2160 CNR2 CB2 CB2 1 0.9 Additionally CB2 receptors which normally exist primarily in the periphery are dramatically 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 76745 17241118 98809 20996 11179 SOD1 ALS ALS 10 1.7 In G93A-SOD1 mutant mice the most well-characterized animal model of ALS endogenous cannabinoids are elevated in spinal cords of symptomatic mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00113214309859518<>ScoreDetail__5468|IGFALS|0.00054973582139694__11179|SOD1|0.00113214309859518__ 0 0 0 0 0 76746 17241118 98811 4645 2160 CNR2 CB2 CB2 9 0.9 We demonstrate that mRNA receptor binding and function of CB2 but not CB1 receptors are dramatically and selectively up-regulated in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 76747 17241118 98811 4644 2159 CNR1 CB1 CB1 12 0.9 that mRNA receptor binding and function of CB2 but not CB1 receptors are dramatically and selectively up-regulated in spinal cords of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 76748 17241118 98812 4645 2160 CNR2 CB2 CB2 7 0.9 More importantly daily injections of the selective CB2 agonist AM-1241 initiated at symptom onset increase the survival interval 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 76749 17241118 98813 4645 2160 CNR2 CB2 CB2 1 0.9 Therefore CB2 agonists may slow motor neuron degeneration and preserve motor function 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 76750 17241118 98813 20996 11179 SOD1 ALS ALS 21 1.7 function and represent a novel therapeutic modality for treatment of ALS of Arkansas for Medical Sciences Little Rock Arkansas 72205 USA 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00113214309859518<>ScoreDetail__5468|IGFALS|0.00054973582139694__11179|SOD1|0.00113214309859518__ 0 0 0 0 0 67241 17305588 84702 20996 11179 SOD1 ALS ALS 3 0.0 Amyotrophic lateral sclerosis (ALS) ALS is a clinically severe and fatal neurodegenerative disease characterized by 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000905901536738425<>ScoreDetail__5468|IGFALS|0.000267863121944686__11179|SOD1|0.000905901536738425__ 0 0 0 0 0 67242 17305588 84703 20996 11179 SOD1 ALS ALS 8 0.0 While the exact cause of neuronal death in ALS remains unknown it is proposed that multiple molecular defects trigger 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000905901536738425<>ScoreDetail__5468|IGFALS|0.000267863121944686__11179|SOD1|0.000905901536738425__ 0 0 0 0 0 67243 17305588 84705 20996 11179 SOD1 ALS ALS 27 0.0 a pharmacotherapy and in the design of clinical trials in ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000905901536738425<>ScoreDetail__5468|IGFALS|0.000267863121944686__11179|SOD1|0.000905901536738425__ 0 0 0 0 0 67244 17305588 84707 20996 11179 SOD1 ALS ALS 4 0.0 In the context of ALS we review some of the salient issues related to the 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000905901536738425<>ScoreDetail__5468|IGFALS|0.000267863121944686__11179|SOD1|0.000905901536738425__ 0 0 0 0 0 67245 17305588 84707 20996 11179 SOD1 ALS ALS 33 0.0 to assessing studies in translating therapeutic strategies to patients with ALS and discuss therapeutic targets and pharmacological approaches to slowing disease 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000905901536738425<>ScoreDetail__5468|IGFALS|0.000267863121944686__11179|SOD1|0.000905901536738425__ 0 0 0 0 0 67325 17306794 84920 20996 11179 SOD1 ALS ALS 55 1.9 mouse models of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) ALS and Alzheimer's disease (AD) AD 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000516590229165011<>ScoreDetail__5468|IGFALS|0.00031808959679112__11179|SOD1|0.000516590229165011__ 0 0 0 0 0 67326 17306794 84928 926 620 APP APP APP 25 0.6 SOD1-G93A and the Alzheimer's disease double transgenic mouse model APP/PS1 APP PS1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67327 17306794 84928 17461 9508 PSEN1 PS1 PS1 25 0.9 and the Alzheimer's disease double transgenic mouse model APP/PS1 APP PS1 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67328 17306794 84930 20996 11179 SOD1 SOD1 SOD1 16 2.4 copies ( Gurney et al. 1994 of the human mutant SOD1 gene (Cu/Zn-SOD) Cu Zn-SOD containing the Gly 93 _amp_#x2192 Ala 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67329 17306794 84933 926 620 APP amyloid amyloid 5 1.3 Transgenic mice expressing the human amyloid precursor protein (APP) APP with the Swedish mutation (K670M/N671L) K670M 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 67330 17306794 84933 926 620 APP APP APP 8 0.6 Transgenic mice expressing the human amyloid precursor protein (APP) APP with the Swedish mutation (K670M/N671L) K670M N671L and the human 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67331 17306794 84933 17461 9508 PSEN1 PS1 PS1 19 0.9 mutation (K670M/N671L) K670M N671L and the human presenilin 1 (PS1) PS1 carrying the mutation (M146L) M146L under the control of the 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67332 17306794 84933 22143 11801 THY1 THY1 Thy1 30 0.3 the mutation (M146L) M146L under the control of the murine Thy1 promoter were generated on the B6D2F1 genetic background in our 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67333 17306794 84934 926 620 APP APP APP 18 0.6 mice were crossed to generate mice carrying both transgenes (APP/PS1) APP PS1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67334 17306794 84934 17461 9508 PSEN1 PS1 PS1 18 0.9 were crossed to generate mice carrying both transgenes (APP/PS1) APP PS1 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67335 17306794 84957 19573 10691 SDS SDS SDS 10 0.0 Proteins were electrophoretically separated on a 10% polyacrylamide gel containing SDS and transferred onto a PVDF-membrane (Carl Carl Roth Karlsruhe Germany 1 JUMiner_v2.2 1 0 0 2 19440 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:19440|SBDS|0.00036058737944172<>ScoreDetail__10691|SDS|0.000149094781682641__19440|SBDS|0.00036058737944172__ 0 0 0 0 0 67336 17306794 84958 19329 10524 SALL1 TBS TBS 15 0.0 1% BSA in TBS_amp_#x2013 Tween (0.1% 0.1% Tween 20_amp_#xa0 mM TBS at RT for 1_amp_#xa0 h 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67337 17306794 84961 7329 16460 FARP2 FRG FRG 32 0.0 with mouse anti-chick -tubulin (1:400,000; 1 400 000 Sigma Deisenhofen FRG HRP-coupled anti-mouse (1:50,000 1 50 000 in 1.5% milk powder 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67338 17306794 84966 5134 2527 CTSB CATB CATB 6 1.0 Second with recombinant mouse cathepsin B (CATB) CATB and cathepsin L (CATL) CATL (both both R_amp_#x26 D Systems 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 23487 12450 TYRP1 0 67339 17306794 84966 5142 2537 CTSL1 CATL CATL 10 1.3 recombinant mouse cathepsin B (CATB) CATB and cathepsin L (CATL) CATL (both both R_amp_#x26 D Systems loaded membranes were incubated with 1 JUMiner_v2.2 1 0 0 2 2537 TotalCon:2<>2537|CTSL1|1514|Complete__14006|TRPV6|55503|Complete__<>AvaiableGeneRif=2<>BEST:2537|CTSL1|0.000827463702863064<>ScoreDetail__2537|CTSL1|0.000827463702863064__14006|TRPV6|0.000468843346580431__ 0 0 0 0 0 67340 17306794 84990 5134 2527 CTSB CATB CATB 13 1.0 the reaction was followed in the presence of the specific CATB inhibitor CA-074 (1_amp_#xa0;_amp_#x3bc;M, 1_amp_#xa0 _amp_#x3bc M Bachem Weil am Rhein 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 23487 12450 TYRP1 0 67341 17306794 84990 5134 2527 CTSB CATB CATB 35 1.0 E-64 (5_amp_#xa0;_amp_#x3bc;M, 5_amp_#xa0 _amp_#x3bc M Sigma in order to inactivate CATB which is also able to hydrolyze the substrate at these 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 23487 12450 TYRP1 0 67342 17306794 84997 6336 3146 ECE1 ECE1 ECE-1 7 0.5 Cathepsin L cathepsin S as well as ECE-1 activity could be excluded (data data not shown 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67343 17306794 84999 5134 2527 CTSB CATB CATB 13 1.0 calculated as the difference between the resulting fluorescence measured with CATB inhibitor and with E-64 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 23487 12450 TYRP1 0 67344 17306794 85001 926 620 APP amyloid amyloid 3 1.3 The presence of amyloid plaques in APP/PS1 APP PS1 transgenic mice and AD tissues 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 67345 17306794 85001 926 620 APP APP APP 6 0.6 The presence of amyloid plaques in APP/PS1 APP PS1 transgenic mice and AD tissues was confirmed using thioflavine 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67346 17306794 85001 17461 9508 PSEN1 PS1 PS1 6 0.9 The presence of amyloid plaques in APP/PS1 APP PS1 transgenic mice and AD tissues was confirmed using thioflavine S 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67347 17306794 85004 10731 6149 ITGAM CD11b CD11b 29 1.0 form of CATX the microglia/macrophage microglia macrophage marker rat anti-mouse CD11b (anti-CD11b; anti-CD11b 1 50 alpha chain of a leukocyte-associated protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67348 17306794 85063 8254 4235 GFAP GFAP GFAP 13 2.5 a large number of cells expressing CATX and the astrocyte-marker GFAP ( Figs 4 B_amp_#x2013 B_amp_#x2033 or the microglial marker CD11b 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67349 17306794 85063 10731 6149 ITGAM CD11b CD11b 22 1.0 GFAP ( Figs 4 B_amp_#x2013 B_amp_#x2033 or the microglial marker CD11b ( Figs 4 C_amp_#x2013 C_amp_#x2033 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67350 17306794 85064 8254 4235 GFAP GFAP GFAP 6 2.5 The number of CATX(+) CATX cells expressing GFAP or CD11b was substantially increased in aged mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67351 17306794 85064 10731 6149 ITGAM CD11b CD11b 8 1.0 The number of CATX(+) CATX cells expressing GFAP or CD11b was substantially increased in aged mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67352 17306794 85075 20996 11179 SOD1 ALS ALS 12 1.9 the expression pattern and activity profile during the pathogenesis of ALS and AD in transgenic mouse models and patient material of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000516590229165011<>ScoreDetail__5468|IGFALS|0.00031808959679112__11179|SOD1|0.000516590229165011__ 0 0 0 0 0 67353 17306794 85087 20996 11179 SOD1 SOD1 SOD1 15 2.4 blot analysis the first changes of CATX immunostaining in the SOD1 transgenics were notable at the age of 3_amp_#xa0 months a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67354 17306794 85096 926 620 APP APP APP 0 0.6 APP/PS1 APP PS1 and human AD tissue 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67355 17306794 85096 17461 9508 PSEN1 PS1 PS1 0 0.9 APP/PS1 APP PS1 and human AD tissue 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67356 17306794 85097 926 620 APP APP APP 9 0.6 At the age of 9_amp_#xa0 months mice overexpressing both mutant APP and mutant presenilin 1 (APP/PS1) APP PS1 showed numerous thioflavine 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67357 17306794 85097 926 620 APP APP APP 14 0.6 mice overexpressing both mutant APP and mutant presenilin 1 (APP/PS1) APP PS1 showed numerous thioflavine S-positive plaques in the cerebral cortex 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67358 17306794 85097 17461 9508 PSEN1 PS1 PS1 14 0.9 overexpressing both mutant APP and mutant presenilin 1 (APP/PS1) APP PS1 showed numerous thioflavine S-positive plaques in the cerebral cortex and 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67359 17306794 85107 926 620 APP APP APP 6 0.6 In coincidence with the brain of APP/PS1 APP PS1 mice thioflavine S(+) S plaques were surrounded by CATX-loaded 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67360 17306794 85107 17461 9508 PSEN1 PS1 PS1 6 0.9 In coincidence with the brain of APP/PS1 APP PS1 mice thioflavine S(+) S plaques were surrounded by CATX-loaded cells 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67361 17306794 85110 926 620 APP APP APP 80 0.6 mouse and (v) v associated with plaques in the APP/PS1 APP PS1 transgenic mouse and human AD cerebral cortex 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67362 17306794 85110 17461 9508 PSEN1 PS1 PS1 80 0.9 and (v) v associated with plaques in the APP/PS1 APP PS1 transgenic mouse and human AD cerebral cortex 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67363 17306794 85126 5137 2530 CTSE CATE CATE 13 1.3 add another enzyme to the group of cathepsins containing CATD CATE and CATB ( Kenessey et al. 1989 Banay-Schwartz et al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67364 17306794 85126 5134 2527 CTSB CATB CATB 15 1.0 enzyme to the group of cathepsins containing CATD CATE and CATB ( Kenessey et al. 1989 Banay-Schwartz et al. 1992 Nakanishi 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 23487 12450 TYRP1 0 67365 17306794 85133 20996 11179 SOD1 ALS ALS 16 1.9 upregulated in these cells in degenerating brain regions of the ALS transgenic mouse model SOD1-G93A and around senile plaques of APP/PS1 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000516590229165011<>ScoreDetail__5468|IGFALS|0.00031808959679112__11179|SOD1|0.000516590229165011__ 0 0 0 0 0 67366 17306794 85133 926 620 APP APP APP 26 0.6 transgenic mouse model SOD1-G93A and around senile plaques of APP/PS1 APP PS1 transgenics and AD patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67367 17306794 85133 17461 9508 PSEN1 PS1 PS1 26 0.9 mouse model SOD1-G93A and around senile plaques of APP/PS1 APP PS1 transgenics and AD patients 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67368 17306794 85134 5134 2527 CTSB CATB CATB 14 1.0 in line with the plaque-associated deposition of other cathepsins like CATB CATD and CATS ( Cataldo and Nixon 1990 Bernstein et 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 23487 12450 TYRP1 0 67369 17306794 85142 5134 2527 CTSB CATB CATB 21 1.0 reports showing a strong interaction of several cathepsins such as CATB CATL and CATD with inflammatory factors ( Bever et al. 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 23487 12450 TYRP1 0 67370 17306794 85142 5142 2537 CTSL1 CATL CATL 22 1.3 showing a strong interaction of several cathepsins such as CATB CATL and CATD with inflammatory factors ( Bever et al. 1989 1 JUMiner_v2.2 1 0 0 2 2537 TotalCon:2<>2537|CTSL1|1514|Complete__14006|TRPV6|55503|Complete__<>AvaiableGeneRif=2<>BEST:2537|CTSL1|0.000827463702863064<>ScoreDetail__2537|CTSL1|0.000827463702863064__14006|TRPV6|0.000468843346580431__ 0 0 0 0 0 67371 17306794 85142 5142 2537 CTSL1 CATL CATL 50 1.3 Schmid et al. 2002 and a role of CATS and CATL in antigen presentation ( Villadangos et al. 1997 Nakagawa et 1 JUMiner_v2.2 1 0 0 2 2537 TotalCon:2<>2537|CTSL1|1514|Complete__14006|TRPV6|55503|Complete__<>AvaiableGeneRif=2<>BEST:2537|CTSL1|0.000827463702863064<>ScoreDetail__2537|CTSL1|0.000827463702863064__14006|TRPV6|0.000468843346580431__ 0 0 0 0 0 67372 17306794 85145 14317 7762 NEUROD1 BETA2 beta2 4 1.0 Via an interaction with beta2 integrins ( Obermajer et al. 2006 it might influence cell 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67373 17306794 85154 20996 11179 SOD1 ALS ALS 29 1.9 et al. 2001 and Deng et al. 2001 and in ALS ( Wootz et al. 2006 and could thereby modulate or 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000516590229165011<>ScoreDetail__5468|IGFALS|0.00031808959679112__11179|SOD1|0.000516590229165011__ 0 0 0 0 0 67374 17306794 85181 8254 4235 GFAP GFAP GFAP 21 2.5 with the neuron-marker NeuN (A, A A_amp_#x2032 A_amp_#x2033 the astrocyte-marker GFAP (B, B B_amp_#x2032 B_amp_#x2033 and the microglia-marker CD11b (C, C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67375 17306794 85181 10731 6149 ITGAM CD11b CD11b 28 1.0 the astrocyte-marker GFAP (B, B B_amp_#x2032 B_amp_#x2033 and the microglia-marker CD11b (C, C C_amp_#x2032 C_amp_#x2033 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67376 17306794 85210 926 620 APP APP APP 4 0.6 Fig 8._amp_#xa0 CATX expression in APP/PS1 APP PS1 bigenic mice and Alzheimer patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67377 17306794 85210 17461 9508 PSEN1 PS1 PS1 4 0.9 Fig 8._amp_#xa0 CATX expression in APP/PS1 APP PS1 bigenic mice and Alzheimer patients 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67378 17306794 85211 926 620 APP APP APP 1 0.6 (A_amp_#x2013;D) A_amp_#x2013 D APP/PS1 APP PS1 bigenic animals 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67379 17306794 85211 17461 9508 PSEN1 PS1 PS1 1 0.9 (A_amp_#x2013;D) A_amp_#x2013 D APP/PS1 APP PS1 bigenic animals 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67380 17306794 85212 926 620 APP amyloid amyloid 8 1.3 A A_amp_#x2032 Thioflavine and CATX staining of an amyloid plaque in the cerebral cortex of a 9-month-old APP/PS1 APP 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 67381 17306794 85212 926 620 APP APP APP 17 0.6 amyloid plaque in the cerebral cortex of a 9-month-old APP/PS1 APP PS1 bigenic animal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 67382 17306794 85212 17461 9508 PSEN1 PS1 PS1 17 0.9 plaque in the cerebral cortex of a 9-month-old APP/PS1 APP PS1 bigenic animal 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>9508|PSEN1|5663|Complete__20640|TAS2R62P|338399|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 67617 17311555 85701 20996 11179 SOD1 ALS ALS 38 0.0 rheumatoid arthritis traumatic brain injury and amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000826422729474794<>ScoreDetail__5468|IGFALS|0.000270343336036767__11179|SOD1|0.000826422729474794__ 0 0 0 0 0 69184 17350694 88332 20996 11179 SOD1 ALS ALS 10 0.5 AD Parkinson's disease (PD) PD and amyotrophic lateral sclerosis (ALS) ALS are among the best examples of neurodegenerative disorders associated with 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000948068072053173<>ScoreDetail__5468|IGFALS|0.000363147764825507__11179|SOD1|0.000948068072053173__ 0 0 0 0 0 69185 17350694 88351 20996 11179 SOD1 ALS ALS 20 0.5 or cerebrospinal fluid of individuals affected with AD PD and ALS 3 and 9 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000948068072053173<>ScoreDetail__5468|IGFALS|0.000363147764825507__11179|SOD1|0.000948068072053173__ 0 0 0 0 0 69186 17350694 88353 9353 4931 HLA-A MHC MHC 4 0.6 Since the discovery of MHC class II antigens in the microglia surrounding amyloid plaques and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69187 17350694 88353 926 620 APP amyloid amyloid 12 1.0 discovery of MHC class II antigens in the microglia surrounding amyloid plaques and dystrophic neuritis several inflammatory processes have been described 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 69188 17350694 88366 20996 11179 SOD1 ALS ALS 13 0.5 process has been described in the brains of individuals with ALS and a correlation between the intensity of inflammation and progression 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000948068072053173<>ScoreDetail__5468|IGFALS|0.000363147764825507__11179|SOD1|0.000948068072053173__ 0 0 0 0 0 69189 17350694 88367 20996 11179 SOD1 ALS ALS 19 0.5 the number of activated microglia is greater in individuals with ALS than in controls 17 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000948068072053173<>ScoreDetail__5468|IGFALS|0.000363147764825507__11179|SOD1|0.000948068072053173__ 0 0 0 0 0 69190 17350694 88368 20996 11179 SOD1 ALS ALS 6 0.5 Further evidence of microglial involvement in ALS pathology has come from studies showing pro-survival effects of the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000948068072053173<>ScoreDetail__5468|IGFALS|0.000363147764825507__11179|SOD1|0.000948068072053173__ 0 0 0 0 0 69191 17350694 88368 20996 11179 SOD1 ALS ALS 34 0.5 spinal cord neurons exposed to cerebrospinal fluid from individuals with ALS 18 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000948068072053173<>ScoreDetail__5468|IGFALS|0.000363147764825507__11179|SOD1|0.000948068072053173__ 0 0 0 0 0 69192 17350694 88369 20996 11179 SOD1 SOD1 SOD1 11 0.5 anti-inflammatory agents prolong the survival of transgenic mice expressing human SOD1 with a G93A mutation (hSOD1G93A), hSOD1G93A an animal model of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69193 17350694 88369 20996 11179 SOD1 ALS ALS 22 0.5 a G93A mutation (hSOD1G93A), hSOD1G93A an animal model of familial ALS 19 and a clinical trial exploring the effect of a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000948068072053173<>ScoreDetail__5468|IGFALS|0.000363147764825507__11179|SOD1|0.000948068072053173__ 0 0 0 0 0 69194 17350694 88369 20996 11179 SOD1 ALS ALS 39 0.5 exploring the effect of a immunomodulatory agent in individuals with ALS is currently ongoing 20 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000948068072053173<>ScoreDetail__5468|IGFALS|0.000363147764825507__11179|SOD1|0.000948068072053173__ 0 0 0 0 0 69195 17350694 88372 9353 4931 HLA-A MHC MHC 7 0.6 Normally in fact they do not express MHC molecules which is an essential requirement for cell susceptibility to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69196 17350694 88396 6901 3553 FAAH FAAH FAAH 16 2.2 opening of intracellular Ca 2 stores inhibition of AMT and FAAH antioxidative effects 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69197 17350694 88396 673 473 AMT AMT AMT 14 0.1 2 channels opening of intracellular Ca 2 stores inhibition of AMT and FAAH antioxidative effects 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69198 17350694 88397 23199 12716 TRPV1 TRPV1 TRPV1 3 0.6 _amp_#x2022 Signaling through TRPV1 receptors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69199 17350694 88414 23199 12716 TRPV1 TRPV1 TRPV1 12 0.6 characterized ECS elements often includes the type-1 vanilloid receptor (TRPV1), TRPV1 although this receptor does not strictly belong to the ECS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69200 17350694 88415 23199 12716 TRPV1 TRPV1 TRPV1 2 0.6 In fact TRPV1 has emerged as a key target of the amide N 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69201 17350694 88419 673 473 AMT AMT AMT 24 0.0 uptake of AEA (by by compounds that we term _amp_#x2018 AMT inhibitors_amp_#x2019 35 ( Table 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69202 17350694 88422 23199 12716 TRPV1 TRPV1 TRPV1 19 0.6 dopamine cell survival by potentiating the toxic effects of the TRPV1 agonist capsaicin 37 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69203 17350694 88423 23199 12716 TRPV1 TRPV1 TRPV1 12 0.6 thus conceivable that endocannabinoids such as AEA which activates both TRPV1 and CB 1 receptors 33 might contribute to PD pathophysiology 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69204 17350694 88425 6901 3553 FAAH FAAH FAAH 19 2.2 obtained through genetic ablation of fatty acid amide hydrolase (FAAH) FAAH 38 exert robust anti-inflammatory and neuroprotective effects in hSOD1G93A mice 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69205 17350694 88430 673 473 AMT AMT AMT 13 0.0 also been reported in experimental MS in response to pharmacological AMT inhibitors which can increase levels of AEA 45 and 46 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69206 17350694 88437 673 473 AMT AMT AMT 6 0.0 Promising results have been reported with AMT inhibitors such as AM404 (see see Chemical names VDM11 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69207 17350694 88438 23199 12716 TRPV1 TRPV1 TRPV1 30 0.6 the synthesis of new AEA after the direct activation of TRPV1 by AM404 rather than to AMT inhibition 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69208 17350694 88438 673 473 AMT AMT AMT 36 0.0 the direct activation of TRPV1 by AM404 rather than to AMT inhibition 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69209 17350694 88442 673 473 AMT AMT AMT 2 0.0 Notably another AMT inhibitor UCM707 significantly protects mice against the excitotoxin kainic acid 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69210 17350694 88445 6901 3553 FAAH FAAH FAAH 7 2.2 Several studies have provided strong evidence that FAAH owing to its broad distribution might represent an attractive therapeutic 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69211 17350694 88446 6901 3553 FAAH FAAH FAAH 4 2.2 For example inhibition of FAAH by URB597 can augment endogenous brain levels of AEA and 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69212 17350694 88448 6901 3553 FAAH FAAH FAAH 3 2.2 Similarly AM374 another FAAH inhibitor has been shown to exert potent neuroprotective effects in 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69213 17350694 88450 6901 3553 FAAH FAAH FAAH 5 2.2 Furthermore another selective and powerful FAAH inhibitor that has been used for the treatment of pathological 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69214 17350694 88452 6901 3553 FAAH FAAH FAAH 29 2.2 on the endocannabinoid tone and thus favors the use of FAAH inhibitors to treat the inflammatory and neurodegenerative damage associated with 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69215 17350694 88455 23199 12716 TRPV1 TRPV1 TRPV1 15 0.6 have distinct pharmacological profiles on CB 1 CB 2 and TRPV1 receptors thus it can be anticipated that differential modulation of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69216 17350694 88456 23199 12716 TRPV1 TRPV1 TRPV1 27 0.6 with the fact that AEA but not 2-AG binds to TRPV1 33 suggests that agents that can modulate 2-AG levels within 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69217 17350694 88458 23199 12716 TRPV1 TRPV1 TRPV1 4 0.6 By contrast stimulation of TRPV1 favors inflammation 27 as a result modulation of AEA-dependent activation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69218 17350694 88463 14093 21683 NAPEPLD NAPE-PLD NAPE-PLD 69 1.3 been for N -acylphosphatidylethanolamine (NAPE)-specific NAPE -specific phospholipase D (NAPE-PLD) NAPE-PLD 59 and FAAH 60 and 61 with respect to AEA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69219 17350694 88463 6901 3553 FAAH FAAH FAAH 72 2.2 -acylphosphatidylethanolamine (NAPE)-specific NAPE -specific phospholipase D (NAPE-PLD) NAPE-PLD 59 and FAAH 60 and 61 with respect to AEA 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69220 17350694 88464 23199 12716 TRPV1 TRPV1 TRPV1 13 0.6 that our hypothesis that a balance between CB receptors and TRPV1 modulates the dual nature of neurological diseases finds a nice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69221 17350694 88464 23199 12716 TRPV1 TRPV1 TRPV1 35 0.6 in pathological pain sensation where it has been demonstrated that TRPV1 functions to oppose CB-receptor-dependent effects 62 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69222 17350694 88475 6901 3553 FAAH FAAH FAAH 18 2.2 AEA seems to be largely dependent on its hydrolysis by FAAH rather than on its synthesis by Ca 2 -dependent N 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69223 17350694 88475 14093 21683 NAPEPLD NAPE-PLD NAPE-PLD 31 1.3 on its synthesis by Ca 2 -dependent N -acyltransferase or NAPE-PLD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69224 17350694 88477 14093 21683 NAPEPLD NAPE-PLD NAPE-PLD 9 1.3 If not therapeutic agents per se inhibitors of NAPE-PLD FAAH AMT DAGL or MAGL could be used together with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69225 17350694 88477 6901 3553 FAAH FAAH FAAH 10 2.2 If not therapeutic agents per se inhibitors of NAPE-PLD FAAH AMT DAGL or MAGL could be used together with AEA 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69226 17350694 88477 673 473 AMT AMT AMT 11 0.3 If not therapeutic agents per se inhibitors of NAPE-PLD FAAH AMT DAGL or MAGL could be used together with AEA or 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69227 17350694 88479 6901 3553 FAAH FAAH FAAH 10 2.2 The mechanism of action of cannabidiol relies on AMT and FAAH inhibition and on antioxidative properties as a result this natural 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69228 17350694 88479 673 473 AMT AMT AMT 8 0.1 The mechanism of action of cannabidiol relies on AMT and FAAH inhibition and on antioxidative properties as a result 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69229 17350694 88486 1760 1103 BRD2 NAT NAT 37 0.0 a Ca 2 -dependent N -acyltransferase or trans -acylase (NAT) NAT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69230 17350694 88487 14093 21683 NAPEPLD NAPE-PLD NAPE-PLD 5 1.3 NArPE is then cleaved by NAPE-PLD a recently characterized phospholipase D which releases AEA and phosphatidic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69231 17350694 88488 673 473 AMT AMT AMT 29 0.0 occurs through cellular uptake by a purported high-affinity transporter (AMT) AMT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69232 17350694 88489 673 473 AMT AMT AMT 7 0.0 As yet the existence of a true AMT is a matter of debate and it is possible that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69233 17350694 88490 6901 3553 FAAH FAAH FAAH 13 2.2 up by cells AEA is a substrate for the hydrolase FAAH which breaks the amide bond and releases arachidonic acid and 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69234 17350694 88493 673 473 AMT AMT AMT 24 0.0 purported 2-AG membrane transporter that might be the same as AMT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69235 17350694 88494 6901 3553 FAAH FAAH FAAH 10 2.2 Once accumulated in the cell 2-AG can be degraded by FAAH or more efficiently by a specific MAGL 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69236 17350694 88497 23199 12716 TRPV1 TRPV1 TRPV1 0 0.6 TRPV1 is another key molecular target of AEA but importantly not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69237 17350694 88498 23199 12716 TRPV1 TRPV1 TRPV1 21 0.6 CB 1 or CB 2 receptors and by AEA through TRPV1 are summarized in Box 1 along with the biological actions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69238 17350694 88499 6901 3553 FAAH FAAH FAAH 13 2.2 the ECS are located in the plasma membrane apart from FAAH which is bound to intracellular membranes and MAGL which is 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 69239 17350694 88501 23199 12716 TRPV1 TRPV1 TRPV1 12 0.6 one hand AEA might control inflammatory processes by binding to TRPV1 such that drugs that are able to modulate the AEA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69240 17350694 88501 14093 21683 NAPEPLD NAPE-PLD NAPE-PLD 25 1.3 drugs that are able to modulate the AEA metabolic enzymes NAPE-PLD and FAAH might be exploited to curb neuroinflammation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 69241 17350694 88501 6901 3553 FAAH FAAH FAAH 27 2.2 are able to modulate the AEA metabolic enzymes NAPE-PLD and FAAH might be exploited to curb neuroinflammation 1 JUMiner_v2.2 1 0 0 2 3553 TotalCon:2<>3553|FAAH|2166|Complete__21197|FA2H|79152|Complete__<>AvaiableGeneRif=2<>BEST:3553|FAAH|0.000667783686651611<>ScoreDetail__21197|FA2H|0.000335739466174249__3553|FAAH|0.000667783686651611__ 0 0 0 0 0 60778 17418957 76946 22551 11892 TNF TNF TNF-A 18 1.2 fluid levels of the inflammatory cytokine tumor necrosis factor-alpha (TNF-_amp_#x3b1;) TNF-_amp_#x3b1 have been implicated in the pathogenesis of amyotrophic lateral sclerosis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60779 17418957 76946 20996 11179 SOD1 ALS ALS 29 0.5 been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60780 17418957 76947 20996 11179 SOD1 ALS ALS 6 0.5 The mechanism of neuron death in ALS remains unclear along with the contributions of mitochondrial dysfunction and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60781 17418957 76948 22551 11892 TNF TNF TNF-A 20 1.2 cords were established and directly exposed in vitro to recombinant TNF-_amp_#x3b1 for varying lengths of time 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60782 17418957 76950 22551 11892 TNF TNF TNF-A 4 1.2 Our results demonstrate that TNF-_amp_#x3b1 induced mitochondrial redistribution toward the soma in MN 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60783 17418957 76951 20996 11179 SOD1 ALS ALS 15 0.5 precede and in fact cause the mitochondrial changes observed in ALS tissue 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60784 17418957 76952 20996 11179 SOD1 ALS ALS 3 0.5 Amyotrophic lateral sclerosis (ALS) ALS is a common fatal neurodegenerative disease which involves the degeneration 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60785 17418957 76953 20996 11179 SOD1 ALS ALS 3 0.5 The pathogenesis of ALS most likely reflects a multifaceted interaction of genetic factors ( 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60786 17418957 76954 20996 11179 SOD1 ALS ALS 9 0.5 Mitochondrial dysfunction is involved in the cellular pathology of ALS ( Orrell and Schapira 2002 and Hervias et al 2005 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60787 17418957 76955 20996 11179 SOD1 ALS ALS 2 0.5 Mitochondria in ALS have been shown to have impaired electron transport increased free 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60788 17418957 76957 20996 11179 SOD1 SOD1 SOD1 19 0.5 the onset of MN degeneration in mice expressing a mutant SOD1 ( Kong and Xu 1998 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60789 17418957 76958 20996 11179 SOD1 ALS ALS 13 0.5 ultrastructurally abnormal mitochondria occur at the synapses of MN from ALS patients ( Sasaki and Iwata 1999 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60790 17418957 76959 20996 11179 SOD1 ALS ALS 9 0.5 In addition ultrastructural studies of anterior horn cells of ALS patients and SOD1 mouse model show accumulation of mitochondria in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60791 17418957 76959 20996 11179 SOD1 SOD1 SOD1 12 0.5 ultrastructural studies of anterior horn cells of ALS patients and SOD1 mouse model show accumulation of mitochondria in the axonal hillock 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60792 17418957 76960 22551 11892 TNF TNF TNF-A 8 1.2 Serum levels of the cytokine tumor necrosis factor-alpha (TNF-_amp_#x3b1;) TNF-_amp_#x3b1 and its soluble receptors have been reported to be elevated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60793 17418957 76960 20996 11179 SOD1 ALS ALS 20 0.5 its soluble receptors have been reported to be elevated in ALS patients as compared with healthy controls ( Poloni et al 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60794 17418957 76961 22551 11892 TNF TNF TNF-A 5 1.2 In the G93A-SOD1 mouse the TNF-_amp_#x3b1 receptor p55 is upregulated between pre-symptomatic and symptomatic stages of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60795 17418957 76961 22561 11916 TNFRSF1A p55 p55 7 1.2 In the G93A-SOD1 mouse the TNF-_amp_#x3b1 receptor p55 is upregulated between pre-symptomatic and symptomatic stages of disease suggesting 1 JUMiner_v2.2 1 0 0 2 8981 TotalCon:5<>8981|PIK3R3|8503|Complete__9557|PSMD12|5718|No_GeneRif__3446|ERG|2078|Complete__11148|FSCN1|6624|Complete__11916|TNFRSF1A|7132|Complete__<>AvaiableGeneRif=4<>BEST:8981|PIK3R3|0.000377719580983078<>ScoreDetail__11916|TNFRSF1A|0.000346084553077064__3446|ERG|0.000363966924505736__11148|FSCN1|0.000316296022954054__8981|PIK3R3|0.000377719580983078__ 0 0 0 0 0 60796 17418957 76961 22551 11892 TNF TNF TNF-A 19 1.2 upregulated between pre-symptomatic and symptomatic stages of disease suggesting that TNF-_amp_#x3b1 and its receptors may be involved in MN degeneration ( 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60797 17418957 76962 22551 11892 TNF TNF TNF-A 0 1.2 TNF-_amp_#x3b1 has been shown to cause or contribute to cell death 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60798 17418957 76962 7708 3811 FOXG1 QIN Qin 60 0.0 2001 Brabers and Nottet 2006 and Nakazawa et al 2006 Qin et al. 2007 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60799 17418957 76963 22551 11892 TNF TNF TNF-A 10 1.2 Previous reports have demonstrated that stimulation of sensitive cells with TNF-_amp_#x3b1 induces abnormal perinuclear clustering of mitochondria from an evenly spread 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60800 17418957 76964 22551 11892 TNF TNF TNF-A 15 1.2 trafficking of mitochondria in MN within neurites is altered by TNF-_amp_#x3b1 an observation that mimics the in vivo histological findings in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60801 17418957 76964 20996 11179 SOD1 ALS ALS 27 0.5 observation that mimics the in vivo histological findings in human ALS and mouse models of the disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60802 17418957 76965 22551 11892 TNF TNF TNF-A 6 1.2 Because of the reported elevation of TNF-_amp_#x3b1 and its receptors ( Poloni et al 2000 Hensley et 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60803 17418957 76965 20996 11179 SOD1 ALS ALS 28 0.5 et al 2002 and Strong 2003 in the setting of ALS and the known positive effects of the TNF-_amp_#x3b1 blocker thalidomide 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60804 17418957 76965 22551 11892 TNF TNF TNF-A 36 1.2 setting of ALS and the known positive effects of the TNF-_amp_#x3b1 blocker thalidomide on the progression of ALS in the SOD1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60805 17418957 76965 20996 11179 SOD1 ALS ALS 43 0.5 effects of the TNF-_amp_#x3b1 blocker thalidomide on the progression of ALS in the SOD1 mouse model ( Wong et al 2004 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60806 17418957 76965 20996 11179 SOD1 SOD1 SOD1 46 0.5 TNF-_amp_#x3b1 blocker thalidomide on the progression of ALS in the SOD1 mouse model ( Wong et al 2004 and Kiaei et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60807 17418957 76965 22551 11892 TNF TNF TNF-A 69 1.2 2006 we initiated experiments to study the biological effects of TNF-_amp_#x3b1 on MN in vitro 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60808 17418957 76966 22551 11892 TNF TNF TNF-A 17 1.2 survival axonal transport necrosis and apoptosis have well-documented responses to TNF-_amp_#x3b1 (both both related to apoptosis and cellular migration and have 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60809 17418957 76966 20996 11179 SOD1 ALS ALS 34 0.5 migration and have well-documented histological characteristics in the setting of ALS ( Sasaki and Iwata 1996 and Sasaki et al 2005 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60810 17418957 76966 22551 11892 TNF TNF TNF-A 59 1.2 vitro studies specifically to evaluate the responses of mitochondria to TNF-_amp_#x3b1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60811 17418957 76969 14565 7896 NPAT E14 E14 21 0.0 Sasco Sprague_amp_#x2013 Dawley rat embryos at gestation day 14 (E14) E14 as described previously ( Hanson et al 1998 and Ullian 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60812 17418957 76971 22562 11917 TNFRSF1B p75 p75 20 1.2 MNs by positive selection immuno-panning using antibody against the low-affinity p75 NGF receptor (192 192 antibody was a gift of the 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.00049139332912734<>ScoreDetail__9527|PSIP1|0.000349925290091502__2557|CUX1|0.000385430929248857__10876|SIGLEC7|0.00049139332912734__11917|TNFRSF1B|0.00029371887143749__ 0 0 0 0 0 60813 17418957 76971 14373 7808 NGF NGF NGF 21 0.3 by positive selection immuno-panning using antibody against the low-affinity p75 NGF receptor (192 192 antibody was a gift of the E 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60814 17418957 76973 7361 20442 FBRS FBS FBS 21 0.0 spun down at 1000 r.p.m in the presence of 30% FBS and brought up in serum-free growth medium 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>20442|FBRS|64319|Complete__13587|FBXO8|26269|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 60815 17418957 76974 8240 4232 GDNF GDNF GDNF 19 0.9 Invitrogen 10 ng/ml ng ml each of BDNF CNTF and GDNF (Peprotech, Peprotech Rocky Hill NJ USA 100 _amp_#x3bc;g/ml _amp_#x3bc g 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60816 17418957 76974 13439 1304 MRAP B27 B27 10 0.0 base media (Invitrogen, Invitrogen Carlsbad CA USA was supplemented with B27 (Invitrogen), Invitrogen 10 ng/ml ng ml each of BDNF CNTF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60817 17418957 76974 1624 1033 BDNF BDNF BDNF 16 0.0 with B27 (Invitrogen), Invitrogen 10 ng/ml ng ml each of BDNF CNTF and GDNF (Peprotech, Peprotech Rocky Hill NJ USA 100 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60818 17418957 76974 4649 2169 CNTF CNTF CNTF 17 0.1 B27 (Invitrogen), Invitrogen 10 ng/ml ng ml each of BDNF CNTF and GDNF (Peprotech, Peprotech Rocky Hill NJ USA 100 _amp_#x3bc;g/ml 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60819 17418957 76980 22551 11892 TNF TNF TNF-A 9 1.2 cultures were exposed to 0 or 20 ng/ml ng ml TNF-_amp_#x3b1 (R_amp_#x26;D R_amp_#x26 D Systems Minneapolis MN USA on days 3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60820 17418957 76995 22551 11892 TNF TNF TNF-A 12 1.2 was also evaluated with exposure to 100 ng/ml ng ml TNF-_amp_#x3b1 using TUNEL staining (DeadEndTM DeadEndTM Fluorometric TUNEL System Promega Madison 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60821 17418957 76997 22551 11892 TNF TNF TNF-A 7 1.2 Doses of 100 ng/ml ng ml or lower of TNF-_amp_#x3b1 were used in all experiments 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60822 17418957 76999 22551 11892 TNF TNF TNF-A 27 1.2 washed three times with the medium cells were treated with TNF-_amp_#x3b1 at 20 ng/ml ng ml in growth medium 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60823 17418957 77000 19254 10472 RUNX2 CCD CCD 38 0.0 objective lens and recorded with a Cooke Sensicam QE digital CCD camera (Applied Applied Scientific Instrumentation Eugene OR USA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60824 17418957 77013 22551 11892 TNF TNF TNF-A 2 1.2 For the TNF-_amp_#x3b1 cultures and the same conditions 16 cells were counted from 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60825 17418957 77016 22551 11892 TNF TNF TNF-A 15 1.2 were used to determine velocity of mitochondrial transport in both TNF-_amp_#x3b1 -treated and untreated cell populations 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60826 17418957 77022 22551 11892 TNF TNF TNF-A 2 1.2 For the TNF-_amp_#x3b1 treated cells we looked at five cells from three different 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60827 17418957 77023 22551 11892 TNF TNF TNF-A 9 1.2 There were more cells of sufficient clarity for the TNF-_amp_#x3b1 group 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60828 17418957 77024 22551 11892 TNF TNF TNF-A 22 1.2 left fewer wells as controls and treated the rest with TNF-_amp_#x3b1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60829 17418957 77025 22551 11892 TNF TNF TNF-A 9 1.2 were determined from multiple experiments using 20 ng/ml ng ml TNF-_amp_#x3b1 between 6 and 20 h 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60830 17418957 77031 22551 11892 TNF TNF TNF-A 10 1.2 MN survival and cellular distribution of mitochondria in response to TNF-_amp_#x3b1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60831 17418957 77032 22551 11892 TNF TNF TNF-A 9 1.2 in MN cultures exposed to 100 ng/ml ng ml of TNF-_amp_#x3b1 appeared similar to untreated cultures based on cell numbers and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60832 17418957 77033 22551 11892 TNF TNF TNF-A 32 1.2 of multiple neurites (untreated=23.2_amp_#xb1;2.1 untreated=23.2_amp_#xb1 2.1 neurons/mm neurons mm 2 TNF-_amp_#x3b1 =23.9_amp_#xb1 2.7 neurons/mm neurons mm 2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60833 17418957 77034 22551 11892 TNF TNF TNF-A 13 1.2 the percentage of TUNEL-positive cells was observed after treatment with TNF-_amp_#x3b1 (18_amp_#xb1;4%) 18_amp_#xb1 4% for 2 days at concentrations of 100 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60834 17418957 77035 22551 11892 TNF TNF TNF-A 0 1.2 TNF-_amp_#x3b1 alone was insufficient in inducing MN death in cultures 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60835 17418957 77036 22551 11892 TNF TNF TNF-A 20 1.2 the somas of cells treated with 20 ng/ml ng ml TNF-_amp_#x3b1 ( Fig 2 B D as compared with controls ( 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60836 17418957 77038 22551 11892 TNF TNF TNF-A 11 1.2 of mitochondrial movement in neurites of MN during exposure to TNF-_amp_#x3b1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60837 17418957 77039 22551 11892 TNF TNF TNF-A 48 1.2 and 0.671_amp_#xb1 0.115 _amp_#x3bc;m/s _amp_#x3bc m s for control and TNF-_amp_#x3b1 -treated respectively 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60838 17418957 77040 22551 11892 TNF TNF TNF-A 12 1.2 and 0.704_amp_#xb1 0.117 _amp_#x3bc;m/s _amp_#x3bc m s for control and TNF-_amp_#x3b1 -treated respectively 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60839 17418957 77041 22551 11892 TNF TNF TNF-A 7 1.2 No significant velocity changes were observed with TNF-_amp_#x3b1 treatment as assessed using Student t -test for two-sample comparisons 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60840 17418957 77043 22551 11892 TNF TNF TNF-A 18 1.2 1.5 2_amp_#x2013 4 and 6_amp_#x2013 8 h after treatment with TNF-_amp_#x3b1 to evaluate the time-frame that an increase in MT Green 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60841 17418957 77044 22551 11892 TNF TNF TNF-A 18 1.2 the retrograde-moving was observed after 1.5 h of treatment with TNF-_amp_#x3b1 ( Fig 3 B 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60842 17418957 77045 22551 11892 TNF TNF TNF-A 27 1.2 opposed to the exposure to 20 ng/ml ng ml of TNF-_amp_#x3b1 (stacktnf3.avi) stacktnf3.avi at 6 h 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60843 17418957 77048 22551 11892 TNF TNF TNF-A 7 1.2 Retrograde/anterograde Retrograde anterograde neuritic transport ratios in response to TNF-_amp_#x3b1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60844 17418957 77049 22551 11892 TNF TNF TNF-A 14 1.2 retrograde/anterograde retrograde anterograde mitochondrial movement increases in the presence of TNF-_amp_#x3b1 in vitro 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60845 17418957 77050 22551 11892 TNF TNF TNF-A 4 1.2 In the presence of TNF-_amp_#x3b1 we observed an increase in the retrograde/anterograde retrograde anterograde ratio 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60846 17418957 77051 20996 11179 SOD1 ALS ALS 38 0.5 h representing a typical pattern seen in the histopathology of ALS ( Sasaki and Iwata 1996 and Sasaki et al 2005 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60847 17418957 77052 22551 11892 TNF TNF TNF-A 26 1.2 a unipolar perinuclear cluster has been documented in response to TNF-_amp_#x3b1 in murine L929 cells ( De Vos et al. 1998 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60848 17418957 77053 22551 11892 TNF TNF TNF-A 4 1.2 Our observed effects with TNF-_amp_#x3b1 seem to be greatest at about 4 h and then 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60849 17418957 77062 22551 11892 TNF TNF TNF-A 8 1.2 We are unable to say by what mechanism TNF-_amp_#x3b1 effects the localization and movement of mitochondria in MN 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60850 17418957 77065 22551 11892 TNF TNF TNF-A 7 1.2 We did not see an effect of TNF-_amp_#x3b1 on the average or maximum velocity of anterograde or retrograde 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60851 17418957 77065 22551 11892 TNF TNF TNF-A 31 1.2 the net mitochondrial transport toward the soma in response to TNF-_amp_#x3b1 appears to be related to an increased amount of retrograde 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60852 17418957 77067 22551 11892 TNF TNF TNF-A 14 1.2 ratio of retrograde to anterograde movements the observed changes with TNF-_amp_#x3b1 treatment were significant 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60853 17418957 77072 22551 11892 TNF TNF TNF-A 1 1.2 Whether TNF-_amp_#x3b1 perturbs the ATP distribution in MNs is not known but 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60854 17418957 77072 22551 11892 TNF TNF TNF-A 13 1.2 the ATP distribution in MNs is not known but if TNF-_amp_#x3b1 were able to decrease levels of ATP near the cell 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60855 17418957 77074 22551 11892 TNF TNF TNF-A 0 1.2 TNF-_amp_#x3b1 has been shown to cause or contribute to cell death 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60856 17418957 77074 7708 3811 FOXG1 QIN Qin 60 0.0 2001 Brabers and Nottet 2006 and Nakazawa et al 2006 Qin et al. 2007 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60857 17418957 77075 22551 11892 TNF TNF TNF-A 5 1.2 Previous studies have shown that TNF-_amp_#x3b1 mediates apoptosis in cultured MN and DRG neurons that over-express 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60858 17418957 77075 20996 11179 SOD1 ALS ALS 31 0.5 that associates with axonal spheroid inclusions in degenerating MN of ALS patients ( Robertson et al. 2001 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60859 17418957 77076 22551 11892 TNF TNF TNF-A 6 1.2 Recent studies have demonstrated that the TNF-_amp_#x3b1 blocker thalidomide is effective in increasing survival and delaying progression 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60860 17418957 77076 20996 11179 SOD1 ALS ALS 18 0.5 thalidomide is effective in increasing survival and delaying progression of ALS phenotypes in the SOD1 G93A mouse model ( Wong et 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60861 17418957 77076 20996 11179 SOD1 SOD1 SOD1 22 0.5 increasing survival and delaying progression of ALS phenotypes in the SOD1 G93A mouse model ( Wong et al 2004 and Kiaei 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60862 17418957 77077 22551 11892 TNF TNF TNF-A 1 1.2 Interestingly TNF-_amp_#x3b1 knockout mice are resistant to some forms of neurodegeneration as 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60863 17418957 77077 20996 11179 SOD1 SOD1 SOD1 29 0.5 ( Sriram et al. 2002 yet generation of mice expressing SOD1 G37R or SOD1 G93A mutants in the context of TNF-_amp_#x3b1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60864 17418957 77077 20996 11179 SOD1 SOD1 SOD1 32 0.5 al. 2002 yet generation of mice expressing SOD1 G37R or SOD1 G93A mutants in the context of TNF-_amp_#x3b1 gene knockout did 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60865 17418957 77077 22551 11892 TNF TNF TNF-A 39 1.2 SOD1 G37R or SOD1 G93A mutants in the context of TNF-_amp_#x3b1 gene knockout did not affect the lifespan or the extent 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60866 17418957 77077 20996 11179 SOD1 SOD1 SOD1 54 0.5 affect the lifespan or the extent of MN loss in SOD1 transgenic mice ( Gowing et al. 2006 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60867 17418957 77078 22551 11892 TNF TNF TNF-A 5 1.2 In the G93A-SOD1 mouse the TNF-_amp_#x3b1 receptor p55 is upregulated between presymptomatic and symptomatic stages of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60868 17418957 77078 22561 11916 TNFRSF1A p55 p55 7 1.2 In the G93A-SOD1 mouse the TNF-_amp_#x3b1 receptor p55 is upregulated between presymptomatic and symptomatic stages of disease suggesting 1 JUMiner_v2.2 1 0 0 2 8981 TotalCon:5<>8981|PIK3R3|8503|Complete__9557|PSMD12|5718|No_GeneRif__3446|ERG|2078|Complete__11148|FSCN1|6624|Complete__11916|TNFRSF1A|7132|Complete__<>AvaiableGeneRif=4<>BEST:8981|PIK3R3|0.000377719580983078<>ScoreDetail__11916|TNFRSF1A|0.000346084553077064__3446|ERG|0.000363966924505736__11148|FSCN1|0.000316296022954054__8981|PIK3R3|0.000377719580983078__ 0 0 0 0 0 60869 17418957 77078 22551 11892 TNF TNF TNF-A 19 1.2 upregulated between presymptomatic and symptomatic stages of disease suggesting that TNF-_amp_#x3b1 and its receptors may connect inflammation to apoptosis in ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60870 17418957 77078 20996 11179 SOD1 ALS ALS 29 0.5 TNF-_amp_#x3b1 and its receptors may connect inflammation to apoptosis in ALS ( Hensley et al. 2002 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60871 17418957 77079 22551 11892 TNF TNF TNF-A 16 1.2 in isolated MNs was affected on the order of hours TNF-_amp_#x3b1 exposure for several days failed to increase the number of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60872 17418957 77080 22551 11892 TNF TNF TNF-A 3 1.2 The role of TNF-_amp_#x3b1 appears to often require the synergism of other cytokines 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60873 17418957 77081 22551 11892 TNF TNF TNF-A 9 1.2 There is a 20-fold increase in the amount of TNF-_amp_#x3b1 required to kill NSC-34 cells in the absence of LPS-activated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60874 17418957 77081 22551 11892 TNF TNF TNF-A 31 1.2 indicating that microglia secrete a factor(s) factor s that facilitate TNF-_amp_#x3b1 mediated MN death in vitro ( He et al. 2002 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60875 17418957 77081 24053 12728 VWS LPS LPS-activated 19 0.0 TNF-_amp_#x3b1 required to kill NSC-34 cells in the absence of LPS-activated BV-2 microglial supernatant indicating that microglia secrete a factor(s) factor 11 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 60876 17418957 77082 20996 11179 SOD1 ALS ALS 5 0.5 There is increasing evidence that ALS is not just a disease of MN and that neighboring 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60877 17418957 77083 22551 11892 TNF TNF TNF-A 4 1.2 Our data suggest that TNF-_amp_#x3b1 alone is not sufficient to cause apoptosis in our isolated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60878 17418957 77084 22551 11892 TNF TNF TNF-A 12 1.2 of mitochondria closer to the cell body in response to TNF-_amp_#x3b1 could predispose cells to elevated levels of reactive oxygen species 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60879 17418957 77086 22551 11892 TNF TNF TNF-A 14 1.2 shown effects on neuritic transport of mitochondria with the cytokine TNF-_amp_#x3b1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60880 17418957 77087 22551 11892 TNF TNF TNF-A 8 1.2 The observed redistribution of mitochondria in response to TNF-_amp_#x3b1 is similar to that observed in the MN of ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60881 17418957 77087 20996 11179 SOD1 ALS ALS 18 0.5 TNF-_amp_#x3b1 is similar to that observed in the MN of ALS patients a disease which has been shown to have elevated 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 60882 17418957 77087 22551 11892 TNF TNF TNF-A 31 1.2 disease which has been shown to have elevated levels of TNF-_amp_#x3b1 in the spinal cord and serum 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60883 17418957 77088 22551 11892 TNF TNF TNF-A 20 1.2 necrosis which may require the presence of glial cells for TNF-_amp_#x3b1 to be effective 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60884 17418957 77089 14535 7873 NOS2A iNOS iNOS 11 1.0 also plan to evaluate apoptosis and necrosis as well as iNOS production in response to a variety of cytokines 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 60885 17418957 77090 20996 11179 SOD1 ALS ALS 19 0.5 glia and secreted cytokines is involved in MN degeneration and ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000611016399378423<>ScoreDetail__5468|IGFALS|0.000375697724345213__11179|SOD1|0.000611016399378423__ 0 0 0 0 0 63131 17439481 80138 20996 11179 SOD1 ALS ALS 13 1.7 suppresses symptom onset and progression of G93A-SOD1 mouse model of ALS by preventing motor neuron death and inflammation 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00147096540591102<>ScoreDetail__5468|IGFALS|0.00078717618434235__11179|SOD1|0.00147096540591102__ 0 0 0 0 0 63132 17439481 80139 20996 11179 SOD1 ALS ALS 18 1.7 enhanced death signals are involved in amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00147096540591102<>ScoreDetail__5468|IGFALS|0.00078717618434235__11179|SOD1|0.00147096540591102__ 0 0 0 0 0 63133 17439481 80140 6708 3415 EPO EPO EPO 1 1.0 Erythropoietin (EPO) EPO has recently been highlighted as a cytokine with various potent 1 JUMiner_v2.2 1 0 0 2 3415 TotalCon:3<>3415|EPO|2056|Complete__3423|EPX|8288|Complete__11820|TIMP1|7076|Complete__<>AvaiableGeneRif=3<>BEST:3415|EPO|0.001203696513163<>ScoreDetail__3423|EPX|0.000538647993536224__3415|EPO|0.001203696513163__11820|TIMP1|0.000692928852029681__ 0 0 0 0 0 63134 17439481 80141 6708 3415 EPO EPO EPO 11 1.0 study was undertaken to evaluate the effect of recombinant human EPO (rhEPO) rhEPO on ALS model mice 1 JUMiner_v2.2 1 0 0 2 3415 TotalCon:3<>3415|EPO|2056|Complete__3423|EPX|8288|Complete__11820|TIMP1|7076|Complete__<>AvaiableGeneRif=3<>BEST:3415|EPO|0.001203696513163<>ScoreDetail__3423|EPX|0.000538647993536224__3415|EPO|0.001203696513163__11820|TIMP1|0.000692928852029681__ 0 0 0 0 0 63135 17439481 80141 20996 11179 SOD1 ALS ALS 14 1.7 evaluate the effect of recombinant human EPO (rhEPO) rhEPO on ALS model mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00147096540591102<>ScoreDetail__5468|IGFALS|0.00078717618434235__11179|SOD1|0.00147096540591102__ 0 0 0 0 0 63136 17439481 80142 20996 11179 SOD1 ALS ALS 3 1.7 We treated 96 ALS model mice with vehicle only or 1 2.5 or 5 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00147096540591102<>ScoreDetail__5468|IGFALS|0.00078717618434235__11179|SOD1|0.00147096540591102__ 0 0 0 0 0 63137 17439481 80144 20996 11179 SOD1 ALS ALS 13 1.7 that treatment with rhEPO represents a potential therapeutic strategy for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00147096540591102<>ScoreDetail__5468|IGFALS|0.00078717618434235__11179|SOD1|0.00147096540591102__ 0 0 0 0 0 57132 17555556 72109 20996 11179 SOD1 SOD1 mSOD1 10 1.9 studies suggest that microglia over-expressing mutant human superoxide dismutase (mSOD1 mSOD1 G93A may contribute to motoneuron death in a transgenic mouse 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57133 17555556 72110 20996 11179 SOD1 SOD1 mSOD1 9 1.9 To further assess the relative neurotoxicity of wild-type microglia mSOD1 G93A microglia and microglia over-expressing wild-type human SOD1 we used 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57134 17555556 72110 20996 11179 SOD1 SOD1 SOD1 17 1.9 wild-type microglia mSOD1 G93A microglia and microglia over-expressing wild-type human SOD1 we used primary cultures of microglia and motoneurons in the 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57135 17555556 72111 20996 11179 SOD1 SOD1 mSOD1 4 1.9 Following activation with lipopolysaccharide mSOD1 G93A microglia released more nitric oxide more superoxide and less 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57136 17555556 72112 20996 11179 SOD1 SOD1 mSOD1 3 1.9 In microglia/motoneuron microglia motoneuron co-cultures mSOD1 G93A microglia induced more motoneuron death and decreased neurite numbers 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57137 17555556 72113 20996 11179 SOD1 SOD1 SOD1 1 1.9 Mutant SOD1 G93A microglia also induced more motoneuron injury than microglia over-expressing 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57138 17555556 72113 20996 11179 SOD1 SOD1 SOD1 14 1.9 also induced more motoneuron injury than microglia over-expressing wild-type human SOD1 in microglia/motoneuron microglia motoneuron co-cultures 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57139 17555556 72114 20996 11179 SOD1 SOD1 mSOD1 11 1.9 Motoneuron survival was inversely correlated with nitrate nitrite concentrations in mSOD1 G93A co-cultures suggesting the important role of nitric oxide in 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57140 17555556 72115 20996 11179 SOD1 SOD1 mSOD1 5 1.9 Thus relative to wild-type microglia mSOD1 G93A microglia were more neurotoxic and induced more motoneuron injury 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57141 17555556 72116 20996 11179 SOD1 ALS ALS 3 1.9 Amyotrophic lateral sclerosis (ALS) ALS is a progressive neurodegenerative disease characterized by the selective loss 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00146837970366485<>ScoreDetail__5468|IGFALS|0.000620334567109861__11179|SOD1|0.00146837970366485__ 0 0 0 0 0 57142 17555556 72118 20996 11179 SOD1 ALS ALS 21 1.9 recently been considered as important contributors to the pathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00146837970366485<>ScoreDetail__5468|IGFALS|0.000620334567109861__11179|SOD1|0.00146837970366485__ 0 0 0 0 0 57143 17555556 72119 20996 11179 SOD1 ALS ALS 18 1.9 have been demonstrated in the affected areas of tissue from ALS patients ( Engelhardt et al 1993 Henkel et al 2004 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00146837970366485<>ScoreDetail__5468|IGFALS|0.000620334567109861__11179|SOD1|0.00146837970366485__ 0 0 0 0 0 57144 17555556 72120 20996 11179 SOD1 SOD1 mSOD1 12 1.9 human mutant Cu 2 /Zn Zn 2 superoxide dismutase (mSOD1), mSOD1 an animal model of familial ALS immune/inflammatory immune inflammatory changes 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57145 17555556 72120 20996 11179 SOD1 ALS ALS 18 1.9 2 superoxide dismutase (mSOD1), mSOD1 an animal model of familial ALS immune/inflammatory immune inflammatory changes have been observed at early symptomatic 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00146837970366485<>ScoreDetail__5468|IGFALS|0.000620334567109861__11179|SOD1|0.00146837970366485__ 0 0 0 0 0 57146 17555556 72120 20996 11179 SOD1 ALS ALS 55 1.9 suggesting a role for these factors in the pathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00146837970366485<>ScoreDetail__5468|IGFALS|0.000620334567109861__11179|SOD1|0.00146837970366485__ 0 0 0 0 0 57147 17555556 72121 20996 11179 SOD1 SOD1 mSOD1 4 1.9 The selective over-expression of mSOD1 in motoneurons alone does not appear to be sufficient to 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57148 17555556 72121 20996 11179 SOD1 SOD1 mSOD1 22 1.9 be sufficient to fully reproduce the motoneuron disease observed in mSOD1 mice ( Pramatarova et al 2001 Lino et al 2002 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57149 17555556 72123 20996 11179 SOD1 SOD1 mSOD1 1 1.9 In mSOD1 transgenic mice microglial activation is evident prior to the onset 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57150 17555556 72125 20996 11179 SOD1 SOD1 mSOD1 10 1.9 An earlier in vivo study with chimeric mice suggested that mSOD1 glia may contribute to motoneuron injury while wild-type glia may 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57151 17555556 72126 14535 7873 NOS2A iNOS iNOS 19 2.8 by lipopolysaccharide (LPS) LPS up-regulated inducible nitric oxide synthase (iNOS) iNOS expression and released nitric oxide and superoxide which were cytotoxic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57152 17555556 72126 24053 12728 VWS LPS LPS 13 0.0 studies have demonstrated that primary microglia activated by lipopolysaccharide (LPS) LPS up-regulated inducible nitric oxide synthase (iNOS) iNOS expression and released 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57153 17555556 72128 20996 11179 SOD1 SOD1 mSOD1 16 1.9 viability was confirmed in vivo by bone marrow transplantation of mSOD1 G93A /PU.1 PU.1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 mice in which replacing 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57154 17555556 72128 21160 11241 SPI1 PU.1 PU.1 18 1.0 in vivo by bone marrow transplantation of mSOD1 G93A /PU.1 PU.1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 mice in which replacing SOD1 G93A microglia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57155 17555556 72128 20996 11179 SOD1 SOD1 SOD1 24 1.9 G93A /PU.1 PU.1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 mice in which replacing SOD1 G93A microglia with wild-type microglia significantly slowed motoneuron loss prolonged 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57156 17555556 72130 20996 11179 SOD1 SOD1 mSOD1 9 1.9 (2006) 2006 used the Cre-Lox system to document that reducing mSOD1 expression in mSOD1 G37R microglia also resulted in longer disease 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57157 17555556 72130 20996 11179 SOD1 SOD1 mSOD1 12 1.9 the Cre-Lox system to document that reducing mSOD1 expression in mSOD1 G37R microglia also resulted in longer disease duration and survival 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57158 17555556 72130 20996 11179 SOD1 ALS ALS 24 1.9 microglia also resulted in longer disease duration and survival in ALS mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00146837970366485<>ScoreDetail__5468|IGFALS|0.000620334567109861__11179|SOD1|0.00146837970366485__ 0 0 0 0 0 57159 17555556 72131 20996 11179 SOD1 SOD1 mSOD1 18 1.9 evidence comparing the relative toxicity of primary microglia cultures from mSOD1 G93A mice with microglia from their wild-type littermates ( Beers 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57160 17555556 72132 20996 11179 SOD1 SOD1 mSOD1 14 1.9 microglia expressing the human G93A mutation the present paper compares mSOD1 G93A microglia with microglia from mice over-expressing wild-type human SOD1 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57161 17555556 72132 20996 11179 SOD1 SOD1 SOD1 24 1.9 mSOD1 G93A microglia with microglia from mice over-expressing wild-type human SOD1 (wt-hSOD1) wt-hSOD1 as well as microglia from wild-type mice 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57162 17555556 72133 20996 11179 SOD1 SOD1 mSOD1 4 1.9 Our results demonstrate that mSOD1 G93A mouse microglia release more nitric oxide more superoxide and 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57163 17555556 72133 9939 5464 IGF1 IGF1 IGF-1 19 1.2 nitric oxide more superoxide and less insulin-like growth factor-1 (IGF-1) IGF-1 than wild-type microglia 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57164 17555556 72134 20996 11179 SOD1 SOD1 mSOD1 1 1.9 Furthermore mSOD1 G93A microglia induced more motoneuron injury than both wild-type microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57165 17555556 72135 1759 1102 BRD1 BRL BRL 9 0.3 Culture media sera and antibiotics were purchased from Gibco BRL (Rockville, Rockville MD USA and all other reagents were from 1 JUMiner_v2.2 1 2 gibco brl 0 0 0 0 0 0 0 0 57166 17555556 72136 20996 11179 SOD1 SOD1 mSOD1 7 1.9 Experimental animals Mice over-expressing mutant human G93A-SOD1 (mSOD1 mSOD1 G93A B6SJL-TgN SOD1-G93A 1Gur wt-hSOD1 (B6SJL-TgN[SOD1]2Gur), B6SJL-TgN SOD1 2Gur and 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57167 17555556 72136 20996 11179 SOD1 SOD1 SOD1 12 1.9 G93A-SOD1 (mSOD1 mSOD1 G93A B6SJL-TgN SOD1-G93A 1Gur wt-hSOD1 (B6SJL-TgN[SOD1]2Gur), B6SJL-TgN SOD1 2Gur and their non-transgenic littermates were bred and maintained in 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57168 17555556 72140 20996 11179 SOD1 SOD1 mSOD1 6 1.9 Microglial cultures were prepared from 8-day-old mSOD1 G93A mice wt-hSOD1 mice and their non-transgenic littermates as previously 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57169 17555556 72147 24053 12728 VWS LPS LPS 0 0.0 LPS (10 10 or 1 _amp_#x03BC;g/mL) _amp_#x03BC g mL was added 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57170 17555556 72148 9939 5464 IGF1 IGF1 IGF-1 8 1.2 The supernatants were collected for nitric oxide and IGF-1 assays and the cells were collected for western analyses 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57171 17555556 72153 3628 25079 CCDC34 L15 L-15 7 0.3 The cells were then re-suspended in the L-15 culture medium supplemented with sodium bicarbonate (0.2%), 0.2% glucose (3.6 11 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>25079|CCDC34|91057|No_GeneRif__5748|IGKV1D-16|28901|No_GeneRif__<>AvaiableGeneRif=0<> 0 0 0 0 0 57172 17555556 72156 24053 12728 VWS LPS LPS 0 0.0 LPS (10 10 ng/mL ng mL or 1 _amp_#x03BC;g/mL) _amp_#x03BC g 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57173 17555556 72157 14535 7873 NOS2A iNOS iNOS 1 2.8 The iNOS inhibitor L-N 6 -(1-iminoethyl)lysine - 1-iminoethyl lysine hydrochloride (L-NIL, L-NIL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57174 17555556 72157 24053 12728 VWS LPS LPS 16 0.0 _amp_#x03BC;g/mL) _amp_#x03BC g mL was added 1 h prior to LPS treatment in some experiments 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57175 17555556 72158 9939 5464 IGF1 IGF1 IGF-1 11 1.2 supernatants of the co-cultures were collected for nitric oxide and IGF-1 assays and the cells on the coverslips were fixed with 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57176 17555556 72161 19941 10876 SIGLEC7 p75 p75 24 0.3 PBS containing 2% horse serum and then with mouse anti-rat p75 LNTR monoclonal antibody (p75, p75 1 800 Chemicon overnight at 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000450155237357589<>ScoreDetail__9527|PSIP1|0.000260379206808461__2557|CUX1|0.000372136940839946__10876|SIGLEC7|0.000450155237357589__11917|TNFRSF1B|0.000427976438562181__ 0 0 0 0 0 57177 17555556 72161 19941 10876 SIGLEC7 p75 p75 28 0.3 and then with mouse anti-rat p75 LNTR monoclonal antibody (p75, p75 1 800 Chemicon overnight at 4_amp_deg C 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000450155237357589<>ScoreDetail__9527|PSIP1|0.000260379206808461__2557|CUX1|0.000372136940839946__10876|SIGLEC7|0.000450155237357589__11917|TNFRSF1B|0.000427976438562181__ 0 0 0 0 0 57178 17555556 72163 19941 10876 SIGLEC7 p75 p75 9 0.3 Motoneuron survival was assessed by direct counting of large p75 positive cells (cell cell bodies > 30 _amp_#x03BC m displaying 1 JUMiner_v2.2 1 0 0 2 10876 TotalCon:4<>9527|PSIP1|11168|Complete__11917|TNFRSF1B|7133|Complete__2557|CUX1|1523|Complete__10876|SIGLEC7|27036|Complete__<>AvaiableGeneRif=4<>BEST:10876|SIGLEC7|0.000450155237357589<>ScoreDetail__9527|PSIP1|0.000260379206808461__2557|CUX1|0.000372136940839946__10876|SIGLEC7|0.000450155237357589__11917|TNFRSF1B|0.000427976438562181__ 0 0 0 0 0 57179 17555556 72175 20996 11179 SOD1 SOD1 mSOD1 4 1.9 Western blots Wild-type or mSOD1 mouse microglia were incubated at 37_amp_deg C with or without 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57180 17555556 72175 24053 12728 VWS LPS LPS 14 0.0 mouse microglia were incubated at 37_amp_deg C with or without LPS for 48 h 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57181 17555556 72183 3778 10620 CCL21 ECL ECL 1 0.0 The ECL system (Amersham Amersham Biosciences Piscataway NJ USA was used to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57182 17555556 72188 20996 11179 SOD1 SOD SOD 9 1.9 Superoxide assay Superoxide production from microglia was assessed by SOD reduction of ferricytochrome c using a modified protocol of Gao 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57183 17555556 72190 24053 12728 VWS LPS LPS 9 0.0 Microglia were incubated at 37_amp_deg C overnight with and without LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57184 17555556 72196 9939 5464 IGF1 IGF1 IGF-1 2 1.2 ELISA for IGF-1 Insulin-like growth factor-1 ELISA Duoset kit (R R _amp_ D 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57185 17555556 72196 9939 5464 IGF1 IGF1 IGF-1 23 1.2 Minneapolis MN USA was used to determine the concentrations of IGF-1 in cell culture supernatants 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57186 17555556 72199 9939 5464 IGF1 IGF1 IGF-1 16 1.2 the addition of 100 _amp_#x03BC L of samples or mouse IGF-1 standard and incubated for 2 h at 22_amp_deg C 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57187 17555556 72204 20996 11179 SOD1 SOD1 SOD1 1 1.9 Mutant SOD1 G93A microglia produce more neurotoxins and less IGF-1 than wild-type 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57188 17555556 72204 9939 5464 IGF1 IGF1 IGF-1 9 1.2 Mutant SOD1 G93A microglia produce more neurotoxins and less IGF-1 than wild-type microglia 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57189 17555556 72206 20996 11179 SOD1 SOD1 mSOD1 10 1.9 In this study nitric oxide release was compared between primary mSOD1 G93A and wild-type microglia by measuring the nitrate nitrite concentrations 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57190 17555556 72207 20996 11179 SOD1 SOD1 mSOD1 7 1.9 Although nitrate nitrite concentrations from untreated mSOD1 G93A and wild-type microglia were below the linear range of 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57191 17555556 72207 20996 11179 SOD1 SOD1 mSOD1 35 1.9 of nitrate nitrite were within the linear range with both mSOD1 G93A and wild-type microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57192 17555556 72207 24053 12728 VWS LPS LPS 21 0.0 microglia were below the linear range of the assay after LPS stimulation levels of nitrate nitrite were within the linear range 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57193 17555556 72208 20996 11179 SOD1 SOD1 mSOD1 5 1.9 Following 10 ng/mL ng mL LPS treatment mSOD1 G93A microglia produced 4.1 _amp_plusmn 0.58 _amp_#x03BC;mol/L _amp_#x03BC mol L 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57194 17555556 72208 20996 11179 SOD1 SOD1 mSOD1 31 1.9 representing a 73% increase of nitrate/nitrite nitrate nitrite release from mSOD1 G93A microglia compared with wild-type microglia ( p _lt_ 0.01 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57195 17555556 72208 24053 12728 VWS LPS LPS 3 0.1 Following 10 ng/mL ng mL LPS treatment mSOD1 G93A microglia produced 4.1 _amp_plusmn 0.58 _amp_#x03BC;mol/L _amp_#x03BC 6 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57196 17555556 72209 20996 11179 SOD1 SOD1 mSOD1 18 1.9 _amp_plusmn 0.72 _amp_#x03BC;mol/L _amp_#x03BC mol L in the supernatant from mSOD1 G93A microglia and 5.8 _amp_plusmn 0.52 _amp_#x03BC;mol/L _amp_#x03BC mol L 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57197 17555556 72209 24053 12728 VWS LPS LPS 3 0.0 After 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS stimulation nitrate nitrite levels were 8.8 _amp_plusmn 0.72 _amp_#x03BC;mol/L _amp_#x03BC 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57198 17555556 72210 20996 11179 SOD1 SOD1 mSOD1 10 1.9 This represents a 51% increase of nitrate nitrite from mSOD1 G93A microglia compared with wild-type microglia ( p _lt_ 0.05 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57199 17555556 72211 14535 7873 NOS2A iNOS iNOS 19 2.8 of the cultured microglia we measured the protein levels of iNOS in microglia which is the major source of nitric oxide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57200 17555556 72212 14535 7873 NOS2A iNOS iNOS 6 2.8 As demonstrated by western analyses the iNOS expression in untreated microglia was at background levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57201 17555556 72213 20996 11179 SOD1 SOD1 mSOD1 7 1.9 However after treatment with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS mSOD1 G93A microglia expressed 170% more iNOS than wild-type microglia ( 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57202 17555556 72213 14535 7873 NOS2A iNOS iNOS 13 2.8 _amp_#x03BC g mL LPS mSOD1 G93A microglia expressed 170% more iNOS than wild-type microglia ( p _lt_ 0.05 ( Fig 1b 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57203 17555556 72213 24053 12728 VWS LPS LPS 6 0.2 However after treatment with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS mSOD1 G93A microglia expressed 170% more iNOS than wild-type microglia 5 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57204 17555556 72214 20996 11179 SOD1 SOD1 mSOD1 28 1.9 et al 2004 therefore superoxide levels were compared between primary mSOD1 G93A and wild-type microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57205 17555556 72215 20996 11179 SOD1 SOD1 mSOD1 1 1.9 Untreated mSOD1 G93A microglia produced 40% more superoxide than wild-type untreated microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57206 17555556 72216 20996 11179 SOD1 SOD1 mSOD1 6 1.9 After treatment with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS mSOD1 G93A microglia produced 73% more superoxide than similarly treated wild-type 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57207 17555556 72216 20996 11179 SOD1 SOD1 mSOD1 22 1.9 than similarly treated wild-type microglia (370 370 _amp_plusmn 16% in mSOD1 G93A microglia vs 220 _amp_plusmn 23% in wild-type microglia p 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57208 17555556 72216 24053 12728 VWS LPS LPS 5 0.2 After treatment with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS mSOD1 G93A microglia produced 73% more superoxide than similarly treated 5 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57209 17555556 72217 20996 11179 SOD1 SOD SOD 19 1.9 the reduction of ferricytochrome c we added superoxide dismutase (SOD) SOD to the assay to test if the reduction of ferricytochrome 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57210 17555556 72218 20996 11179 SOD1 SOD SOD 3 1.9 The addition of SOD to the assay abolished the reduction of ferricytochrome c suggesting 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57211 17555556 72220 9939 5464 IGF1 IGF1 IGF-1 13 1.2 other previous studies demonstrated that microglia produce significant amounts of IGF-1 ( Butovsky et al 2005 Zhao et al 2006 we 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57212 17555556 72220 9939 5464 IGF1 IGF1 IGF-1 30 1.2 2005 Zhao et al 2006 we measured the presence of IGF-1 in the supernatants of the untreated and LPS-treated microglia cultures 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57213 17555556 72220 24053 12728 VWS LPS LPS-treated 38 0.0 presence of IGF-1 in the supernatants of the untreated and LPS-treated microglia cultures 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57214 17555556 72221 9939 5464 IGF1 IGF1 IGF-1 6 1.2 There was 1100 _amp_plusmn 180 pg/mL pg mL IGF-1 in the untreated wild-type microglia supernatants which was set at 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57215 17555556 72222 20996 11179 SOD1 SOD1 mSOD1 1 1.9 Untreated mSOD1 G93A microglia released 22% less IGF-1 compared with untreated wild-type 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57216 17555556 72222 9939 5464 IGF1 IGF1 IGF-1 7 1.2 Untreated mSOD1 G93A microglia released 22% less IGF-1 compared with untreated wild-type microglia ( p _lt_ 0.01 ( 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57217 17555556 72223 9939 5464 IGF1 IGF1 IGF-1 9 1.2 with 10 or 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS less IGF-1 was measured in both wild-type and mSOD1 G93A microglia 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57218 17555556 72223 20996 11179 SOD1 SOD1 mSOD1 16 1.9 mL LPS less IGF-1 was measured in both wild-type and mSOD1 G93A microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57219 17555556 72223 24053 12728 VWS LPS LPS 7 0.1 After treatment with 10 or 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS less IGF-1 was measured in both wild-type and mSOD1 G93A 6 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57220 17555556 72224 20996 11179 SOD1 SOD1 mSOD1 6 1.9 However using either concentrations of LPS mSOD1 G93A microglia released significantly less IGF-1 than wild-type microglia (10 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57221 17555556 72224 9939 5464 IGF1 IGF1 IGF-1 12 1.2 either concentrations of LPS mSOD1 G93A microglia released significantly less IGF-1 than wild-type microglia (10 10 ng/mL ng mL LPS 21 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57222 17555556 72224 20996 11179 SOD1 SOD1 mSOD1 23 1.9 (10 10 ng/mL ng mL LPS 21 _amp_plusmn 3.4% from mSOD1 G93A microglia and 27 _amp_plusmn 2.4% from wild-type microglia a 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57223 17555556 72224 9939 5464 IGF1 IGF1 IGF-1 39 1.2 2.4% from wild-type microglia a 22% decrease in production of IGF-1 p _lt_ 0.01 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS 18 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57224 17555556 72224 20996 11179 SOD1 SOD1 mSOD1 50 1.9 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS 18 _amp_plusmn 1.7% in mSOD1 G93A microglia and 23 _amp_plusmn 2.2% in wild-type microglia a 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57225 17555556 72224 9939 5464 IGF1 IGF1 IGF-1 66 1.2 2.2% in wild-type microglia a 22% decrease in production of IGF-1 p _lt_ 0.05 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57226 17555556 72224 24053 12728 VWS LPS LPS 5 0.2 However using either concentrations of LPS mSOD1 G93A microglia released significantly less IGF-1 than wild-type microglia 5 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57227 17555556 72224 24053 12728 VWS LPS LPS 18 0.0 less IGF-1 than wild-type microglia (10 10 ng/mL ng mL LPS 21 _amp_plusmn 3.4% from mSOD1 G93A microglia and 27 _amp_plusmn 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57228 17555556 72224 24053 12728 VWS LPS LPS 45 0.0 of IGF-1 p _lt_ 0.01 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS 18 _amp_plusmn 1.7% in mSOD1 G93A microglia and 23 _amp_plusmn 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57229 17555556 72225 20996 11179 SOD1 SOD1 mSOD1 3 1.9 Without LPS treatment mSOD1 G93A microglia released significantly more superoxide and less IGF-1 than 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57230 17555556 72225 9939 5464 IGF1 IGF1 IGF-1 12 1.2 treatment mSOD1 G93A microglia released significantly more superoxide and less IGF-1 than wild-type microglia suggesting that mSOD1 G93A microglia are more 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57231 17555556 72225 20996 11179 SOD1 SOD1 mSOD1 18 1.9 more superoxide and less IGF-1 than wild-type microglia suggesting that mSOD1 G93A microglia are more activated than wild-type microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57232 17555556 72225 24053 12728 VWS LPS LPS 1 0.1 Without LPS treatment mSOD1 G93A microglia released significantly more superoxide and less 6 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57233 17555556 72226 20996 11179 SOD1 SOD1 mSOD1 19 1.9 wild-type microglia did not significantly produce more nitric oxide than mSOD1 G93A microglia treated with 10 ng/mL ng mL LPS 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57234 17555556 72226 24053 12728 VWS LPS LPS 8 0.0 Furthermore in the presence of 100 times more LPS wild-type microglia did not significantly produce more nitric oxide than 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57235 17555556 72226 24053 12728 VWS LPS LPS 26 0.0 than mSOD1 G93A microglia treated with 10 ng/mL ng mL LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57236 17555556 72227 20996 11179 SOD1 SOD1 mSOD1 17 1.9 wild-type microglia did not significantly produce more superoxide than untreated mSOD1 G93A microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57237 17555556 72227 24053 12728 VWS LPS LPS 6 0.0 Even after treatment with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS wild-type microglia did not significantly produce more superoxide than untreated 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57238 17555556 72228 9939 5464 IGF1 IGF1 IGF-1 13 1.2 presence of 100 times less LPS although the amount of IGF-1 released was small mSOD1 G93A microglia did not release significantly 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57239 17555556 72228 20996 11179 SOD1 SOD1 mSOD1 17 1.9 less LPS although the amount of IGF-1 released was small mSOD1 G93A microglia did not release significantly more IGF-1 than wild-type 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57240 17555556 72228 9939 5464 IGF1 IGF1 IGF-1 25 1.2 was small mSOD1 G93A microglia did not release significantly more IGF-1 than wild-type microglia treated with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57241 17555556 72228 24053 12728 VWS LPS LPS 8 0.0 Interestingly in the presence of 100 times less LPS although the amount of IGF-1 released was small mSOD1 G93A 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57242 17555556 72228 24053 12728 VWS LPS LPS 34 0.0 wild-type microglia treated with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL of LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57243 17555556 72229 20996 11179 SOD1 SOD1 mSOD1 4 1.9 These data demonstrated that mSOD1 G93A microglia are more responsive to stimuli than wild-type microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57244 17555556 72230 20996 11179 SOD1 SOD SOD 1 1.9 Mutant SOD G93A microglia co-cultured with motoneurons produce more nitric oxide and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57245 17555556 72230 9939 5464 IGF1 IGF1 IGF-1 13 1.2 microglia co-cultured with motoneurons produce more nitric oxide and less IGF-1 than wild-type microglia Because we demonstrated that primary cultures of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57246 17555556 72231 20996 11179 SOD1 SOD1 mSOD1 6 1.9 Following treatment with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS mSOD1 G93A microglia co-cultured with motoneurons produced significantly more nitrate nitrite 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57247 17555556 72231 20996 11179 SOD1 SOD1 mSOD1 29 1.9 motoneurons (5.4 5.4 _amp_plusmn 0.37 _amp_#x03BC;mol/L _amp_#x03BC mol L in mSOD1 G93A microglia vs 3.3 _amp_plusmn 0.43 _amp_#x03BC;mol/L _amp_#x03BC mol L 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57248 17555556 72231 24053 12728 VWS LPS LPS 5 0.2 Following treatment with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS mSOD1 G93A microglia co-cultured with motoneurons produced significantly more nitrate 5 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57249 17555556 72232 9939 5464 IGF1 IGF1 IGF-1 1 1.2 The IGF-1 levels in untreated mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures were 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57250 17555556 72232 20996 11179 SOD1 SOD1 mSOD1 5 1.9 The IGF-1 levels in untreated mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures were 14% lower than those 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57251 17555556 72233 9939 5464 IGF1 IGF1 IGF-1 10 1.2 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS both co-cultures released less IGF-1 (37 37 _amp_plusmn 2.1% in wild-type microglia and 26 _amp_plusmn 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57252 17555556 72233 20996 11179 SOD1 SOD1 mSOD1 22 1.9 _amp_plusmn 2.1% in wild-type microglia and 26 _amp_plusmn 2.9% in mSOD1 G93A microglia 500 _amp_plusmn 84 pg/mL pg mL corresponds to 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57253 17555556 72233 24053 12728 VWS LPS LPS 5 0.0 After treatment with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS both co-cultures released less IGF-1 (37 37 _amp_plusmn 2.1% in 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57254 17555556 72234 20996 11179 SOD1 SOD1 mSOD1 1 1.9 However mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures released significantly less IGF-1 (30% 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57255 17555556 72234 9939 5464 IGF1 IGF1 IGF-1 8 1.2 However mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures released significantly less IGF-1 (30% 30% decrease than wild-type microglia/motoneuron microglia motoneuron co-cultures ( 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57256 17555556 72235 20996 11179 SOD1 SOD1 SOD1 1 1.9 Mutant SOD1 G93A microglia induce more motoneuron injury than wild-type microglia Because 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57257 17555556 72235 20996 11179 SOD1 SOD1 mSOD1 12 1.9 G93A microglia induce more motoneuron injury than wild-type microglia Because mSOD1 G93A microglia co-cultured with motoneurons produced more nitric oxide and 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57258 17555556 72235 9939 5464 IGF1 IGF1 IGF-1 24 1.2 microglia co-cultured with motoneurons produced more nitric oxide and less IGF-1 than wild-type microglia we asked whether mSOD1 G93A microglia would 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57259 17555556 72235 20996 11179 SOD1 SOD1 mSOD1 31 1.9 oxide and less IGF-1 than wild-type microglia we asked whether mSOD1 G93A microglia would induce more motoneuron injury compared with wild-type 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57260 17555556 72236 20996 11179 SOD1 SOD1 mSOD1 5 1.9 When co-cultured with motoneurons untreated mSOD1 G93A microglia resulted in 17.9% less motoneuron survival than untreated 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57261 17555556 72237 20996 11179 SOD1 SOD1 mSOD1 16 1.9 were decreased 28% when co-cultured with wild-type microglia compared with mSOD1 G93A microglia (12 12 _amp_plusmn 0.7/cell 0.7 cell in WT-Mc 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57262 17555556 72238 20996 11179 SOD1 SOD1 mSOD1 17 1.9 decreased 28% respectively when co-cultured with wild-type microglia compared with mSOD1 G93A microglia (520 520 _amp_plusmn 31 _amp_#x03BC;m/cell _amp_#x03BC m cell 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57263 17555556 72239 20996 11179 SOD1 SOD1 mSOD1 13 1.9 LPS compared with wild-type microglia/motoneuron microglia motoneuron co-cultures co-cultures with mSOD1 G93A microglia had less surviving motoneurons and decreased number and 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57264 17555556 72239 24053 12728 VWS LPS LPS 5 0.0 Following stimulation with 10 ng/mL ng mL LPS compared with wild-type microglia/motoneuron microglia motoneuron co-cultures co-cultures with mSOD1 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57265 17555556 72240 20996 11179 SOD1 SOD1 mSOD1 20 1.9 length were again decreased when the motoneurons were co-cultured with mSOD1 G93A microglia and were compared with similarly treated co-cultures using 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57266 17555556 72240 24053 12728 VWS LPS LPS 5 0.0 After stimulation with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS motoneuron survival and neurite number/length number length were again decreased 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57267 17555556 72241 20996 11179 SOD1 SOD1 mSOD1 8 1.9 More importantly after treatment with 100-fold less LPS mSOD1 G93A microglia did not significantly alter the number of surviving 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57268 17555556 72241 24053 12728 VWS LPS LPS 7 0.2 More importantly after treatment with 100-fold less LPS mSOD1 G93A microglia did not significantly alter the number of 5 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57269 17555556 72241 24053 12728 VWS LPS LPS 28 0.0 with wild-type microglia treated with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57270 17555556 72242 20996 11179 SOD1 SOD1 mSOD1 12 1.9 number and length of motoneuron neurites were significantly less in mSOD1 G93A co-cultures treated with 10 ng/mL ng mL LPS than 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57271 17555556 72242 24053 12728 VWS LPS LPS 19 0.0 in mSOD1 G93A co-cultures treated with 10 ng/mL ng mL LPS than wild-type co-cultures treated with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57272 17555556 72242 24053 12728 VWS LPS LPS 27 0.0 than wild-type co-cultures treated with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS ( p _lt_ 0.05 and p _lt_ 0.02 respectively 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57273 17555556 72244 14535 7873 NOS2A iNOS iNOS 25 2.8 motoneurons we tested if the addition of an inhibitor of iNOS can rescue motoneurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57274 17555556 72245 14535 7873 NOS2A iNOS iNOS 4 2.8 The addition of the iNOS inhibitor L-NIL (100 100 _amp_#x03BC;g/mL) _amp_#x03BC g mL 1 h 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57275 17555556 72245 24053 12728 VWS LPS LPS 13 0.0 (100 100 _amp_#x03BC;g/mL) _amp_#x03BC g mL 1 h prior to LPS (1 1 _amp_#x03BC;g/mL) _amp_#x03BC g mL treatment significantly decreased the 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57276 17555556 72246 20996 11179 SOD1 SOD1 mSOD1 7 1.9 L-NIL also partially rescued motoneurons in both mSOD1 G93A and wild-type co-cultures ( Fig 4b 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57277 17555556 72247 20996 11179 SOD1 SOD1 mSOD1 5 1.9 Motoneuron survival was increased significantly (mSOD1 mSOD1 G93A co-cultures 71 _amp_plusmn 0.9% wild-type co-cultures 86 _amp_plusmn 0.8% 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57278 17555556 72247 20996 11179 SOD1 SOD1 mSOD1 23 1.9 _amp_plusmn 0.8% compared with those treated with LPS only (mSOD1 mSOD1 G93A co-cultures 48 _amp_plusmn 1.8% p _lt_ 0.001 wild-type co-cultures 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57279 17555556 72247 24053 12728 VWS LPS LPS 21 0.1 wild-type co-cultures 86 _amp_plusmn 0.8% compared with those treated with LPS only (mSOD1 mSOD1 G93A co-cultures 48 _amp_plusmn 1.8% p _lt_ 6 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57280 17555556 72250 20996 11179 SOD1 SOD1 mSOD1 12 1.9 the more nitrate nitrite produced the fewer motoneuron survived in mSOD1 G93A and wild-type-co-cultures ( r = _amp_#8722 0.90 p _lt_ 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57281 17555556 72251 20996 11179 SOD1 SOD1 SOD1 1 1.9 Mutant SOD1 G93A microglia are more neurotoxic than wt-hSOD1 microglia Having demonstrated 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57282 17555556 72251 20996 11179 SOD1 SOD1 mSOD1 13 1.9 microglia are more neurotoxic than wt-hSOD1 microglia Having demonstrated that mSOD1 G93A mouse microglia induced more motoneuron injury than wild-type microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57283 17555556 72251 20996 11179 SOD1 SOD1 mSOD1 27 1.9 induced more motoneuron injury than wild-type microglia we asked whether mSOD1 microglia were more neurotoxic than microglia from mice over-expressing wt-hSOD1 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57284 17555556 72253 24053 12728 VWS LPS LPS 5 0.0 After treatment with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS there was increased neurotoxicity of wt-hSOD1 microglia compared with their 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57285 17555556 72254 20996 11179 SOD1 SOD1 mSOD1 16 1.9 of motoneurons fewer neurites and shortening of motoneuron neurites in mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures compared with wt-hSOD1-microglia/motoneuron wt-hSOD1-microglia motoneuron 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57286 17555556 72255 20996 11179 SOD1 SOD1 mSOD1 1 1.9 Therefore mSOD1 G93A microglia induced more motoneuron injury than wt-hSOD1 microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57287 17555556 72256 9939 5464 IGF1 IGF1 IGF-1 13 1.2 not observe significant increase of nitric oxide superoxide or less IGF-1 from wt-hSOD1 microglia compared with their littermate controls ( Table 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57288 17555556 72258 20996 11179 SOD1 SOD1 mSOD1 21 1.9 comparison of the relative neurotoxicity versus neuroprotection of wild-type and mSOD1 microglia from mSOD1 G93A mice and their non-transgenic littermates in 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57289 17555556 72258 20996 11179 SOD1 SOD1 mSOD1 24 1.9 relative neurotoxicity versus neuroprotection of wild-type and mSOD1 microglia from mSOD1 G93A mice and their non-transgenic littermates in the absence and 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57290 17555556 72259 20996 11179 SOD1 SOD1 mSOD1 45 1.9 2006 the present in vitro study demonstrates that microglia from mSOD1 G93A transgenic mice were more activated and more responsive to 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57291 17555556 72259 24053 12728 VWS LPS LPS 56 0.0 G93A transgenic mice were more activated and more responsive to LPS activation than microglia from their non-transgenic wild-type littermates 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57292 17555556 72260 20996 11179 SOD1 SOD1 mSOD1 6 1.9 Additionally when compared with wild-type microglia mSOD1 G93A microglia caused more motoneuron injury in microglia/motoneuron microglia motoneuron 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57293 17555556 72261 22551 11892 TNF TNFA TNF-A 21 0.5 substances such as nitric oxide superoxide and pro-inflammatory cytokines including TNF-A IL-1B and IL-6 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57294 17555556 72261 10463 6018 IL6 IL-6 IL-6 24 1.0 nitric oxide superoxide and pro-inflammatory cytokines including TNF-A IL-1B and IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57295 17555556 72261 10437 5992 IL1B IL-1B IL-1B 22 0.3 such as nitric oxide superoxide and pro-inflammatory cytokines including TNF-A IL-1B and IL-6 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57296 17555556 72262 14535 7873 NOS2A iNOS iNOS 36 2.8 leading to further cell damage ( Mhatre et al 2004 iNOS was found to be up-regulated in a transgenic mouse model 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57297 17555556 72262 20996 11179 SOD1 ALS ALS 49 1.9 to be up-regulated in a transgenic mouse model of familial ALS both in early symptomatic stages and at the end-stage of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00146837970366485<>ScoreDetail__5468|IGFALS|0.000620334567109861__11179|SOD1|0.00146837970366485__ 0 0 0 0 0 57298 17555556 72263 14535 7873 NOS2A iNOS iNOS 2 2.8 Up-regulation of iNOS may in turn stimulate nitric oxide production which plays a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57299 17555556 72263 20996 11179 SOD1 ALS ALS 19 1.9 production which plays a deleterious role in the pathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00146837970366485<>ScoreDetail__5468|IGFALS|0.000620334567109861__11179|SOD1|0.00146837970366485__ 0 0 0 0 0 57300 17555556 72265 20996 11179 SOD1 SOD1 mSOD1 7 1.9 In the present study we demonstrated that mSOD1 G93A microglia expressed more iNOS and released more nitric oxide 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57301 17555556 72265 14535 7873 NOS2A iNOS iNOS 12 2.8 present study we demonstrated that mSOD1 G93A microglia expressed more iNOS and released more nitric oxide and superoxide release relative to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57302 17555556 72270 20996 11179 SOD1 SOD1 mSOD1 13 1.9 nitrate nitrite produced the fewer motoneurons survived in wild-type or mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57303 17555556 72271 14535 7873 NOS2A iNOS iNOS 4 2.8 Furthermore pre-treatment with the iNOS inhibitor (L-NIL) L-NIL prior to LPS treatment significantly decreased nitrate 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57304 17555556 72271 24053 12728 VWS LPS LPS 9 0.0 Furthermore pre-treatment with the iNOS inhibitor (L-NIL) L-NIL prior to LPS treatment significantly decreased nitrate nitrite concentrations and increased motoneuron survival 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57305 17555556 72272 14535 7873 NOS2A iNOS iNOS 9 2.8 Although two earlier reports demonstrated that gene deletion of iNOS or neuronal nitric oxide synthase (nNOS) nNOS does not alter 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57306 17555556 72272 14533 7872 NOS1 nNOS nNOS 15 2.2 gene deletion of iNOS or neuronal nitric oxide synthase (nNOS) nNOS does not alter motoneuron disease in double transgenic iNOS _amp_#8722;/_amp_#8722; 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57307 17555556 72272 14535 7873 NOS2A iNOS iNOS 24 2.8 (nNOS) nNOS does not alter motoneuron disease in double transgenic iNOS _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 /mSOD1 mSOD1 G93A or nNOS _amp_#8722;/_amp_#8722; _amp_#8722 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57308 17555556 72272 20996 11179 SOD1 SOD1 mSOD1 26 1.9 motoneuron disease in double transgenic iNOS _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 /mSOD1 mSOD1 G93A or nNOS _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 /mSOD1 mSOD1 G93A mice 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57309 17555556 72272 14533 7872 NOS1 nNOS nNOS 29 2.2 double transgenic iNOS _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 /mSOD1 mSOD1 G93A or nNOS _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 /mSOD1 mSOD1 G93A mice ( Facchinetti et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57310 17555556 72272 20996 11179 SOD1 SOD1 mSOD1 31 1.9 _amp_#8722 /mSOD1 mSOD1 G93A or nNOS _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 /mSOD1 mSOD1 G93A mice ( Facchinetti et al 1999 Son et al 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57311 17555556 72274 20996 11179 SOD1 SOD1 mSOD1 3 1.9 (2007) 2007 demonstrated that mSOD1 G93A mice with both iNOS alleles deleted have a delayed 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57312 17555556 72274 14535 7873 NOS2A iNOS iNOS 8 2.8 (2007) 2007 demonstrated that mSOD1 G93A mice with both iNOS alleles deleted have a delayed disease progression and a prolonged 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57313 17555556 72275 7333 11920 FAS FAS Fas 9 0.6 Other studies have shown that nitric oxide can induce Fas signaling in mutant SOD1 motoneurons which resulted in mutant SOD1 2 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.00047027456989493<>ScoreDetail__11920|FAS|0.00047027456989493__3594|FASN|0.000389423025326295__ 0 0 0 0 0 57314 17555556 72275 20996 11179 SOD1 SOD1 SOD1 13 1.9 shown that nitric oxide can induce Fas signaling in mutant SOD1 motoneurons which resulted in mutant SOD1 motoneuron death but not 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57315 17555556 72275 20996 11179 SOD1 SOD1 SOD1 19 1.9 Fas signaling in mutant SOD1 motoneurons which resulted in mutant SOD1 motoneuron death but not wild-type motoneurons 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57316 17555556 72276 14533 7872 NOS1 nNOS nNOS 3 2.2 Additionally up-regulation of nNOS was required in this Fas-triggered motoneuron death ( Raoul et 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57317 17555556 72276 7333 11920 FAS FAS Fas-triggered 8 0.6 Additionally up-regulation of nNOS was required in this Fas-triggered motoneuron death ( Raoul et al 2002 2006 1 JUMiner_v2.2 1 0 0 2 11920 TotalCon:2<>11920|FAS|355|Complete__3594|FASN|2194|Complete__<>AvaiableGeneRif=2<>BEST:11920|FAS|0.00047027456989493<>ScoreDetail__11920|FAS|0.00047027456989493__3594|FASN|0.000389423025326295__ 0 0 0 0 0 57318 17555556 72280 9939 5464 IGF1 IGF1 IGF-1 4 1.2 Among these neurotrophic factors IGF-1 has been shown to have a protective effect on motoneurons 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57319 17555556 72281 9939 5464 IGF1 IGF1 IGF-1 0 1.2 IGF-1 is a potent neurotrophic and survival factor ( Vincent et 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57320 17555556 72282 9939 5464 IGF1 IGF1 IGF-1 3 1.2 In contrast free IGF-1 levels in ALS patients_amp_#8217 spinal cords and serum were shown 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57321 17555556 72282 20996 11179 SOD1 ALS ALS 6 1.9 In contrast free IGF-1 levels in ALS patients_amp_#8217 spinal cords and serum were shown to be significantly 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00146837970366485<>ScoreDetail__5468|IGFALS|0.000620334567109861__11179|SOD1|0.00146837970366485__ 0 0 0 0 0 57322 17555556 72282 9939 5464 IGF1 IGF1 IGF-1 43 1.2 al 1998 Wilczak et al 2003 suggesting that down-regulation of IGF-1 trophic support may lead to degeneration of motoneurons 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57323 17555556 72283 9939 5464 IGF1 IGF1 IGF-1 0 1.2 IGF-1 has been reported to prevent glutamate-induced embryonic rat spinal cord 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57324 17555556 72285 20996 11179 SOD1 ALS ALS 10 1.9 2003 successfully prolonged life and delayed disease progression in transgenic ALS mice by enhancing IGF-1 expression in motoneurons 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00146837970366485<>ScoreDetail__5468|IGFALS|0.000620334567109861__11179|SOD1|0.00146837970366485__ 0 0 0 0 0 57325 17555556 72285 9939 5464 IGF1 IGF1 IGF-1 14 1.2 and delayed disease progression in transgenic ALS mice by enhancing IGF-1 expression in motoneurons 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57326 17555556 72286 9939 5464 IGF1 IGF1 IGF-1 8 1.2 A recent study showed that intrathecal injection of IGF-1 into the lumbar spinal cord of transgenic mice expressing the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57327 17555556 72286 20996 11179 SOD1 SOD1 mSOD1 22 1.9 spinal cord of transgenic mice expressing the G93A form of mSOD1 delayed the onset of disease and extended survival ( Nagano 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57328 17555556 72287 9939 5464 IGF1 IGF1 IGF-1 10 1.2 Following activation with LPS the current study demonstrated that free IGF-1 levels were significantly reduced to 20-30% of untreated controls 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57329 17555556 72287 24053 12728 VWS LPS LPS 3 0.0 Following activation with LPS the current study demonstrated that free IGF-1 levels were significantly 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57330 17555556 72288 9939 5464 IGF1 IGF1 IGF-1 12 1.2 represent the first demonstration that wild-type microglia released more free IGF-1 than microglia from mSOD1 G93A transgenic mice either with or 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57331 17555556 72288 20996 11179 SOD1 SOD1 mSOD1 16 1.9 that wild-type microglia released more free IGF-1 than microglia from mSOD1 G93A transgenic mice either with or without LPS stimulation 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57332 17555556 72288 24053 12728 VWS LPS LPS 24 0.0 microglia from mSOD1 G93A transgenic mice either with or without LPS stimulation 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57333 17555556 72289 9939 5464 IGF1 IGF1 IGF-1 2 1.2 Therefore more IGF-1 neurotrophic support from wild-type microglia may also contribute to the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57334 17555556 72290 20996 11179 SOD1 SOD1 mSOD1 5 1.9 Relative to wild-type microglia increased mSOD1 G93A microglial activation induced more motoneuron injury and decreased neurite 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57335 17555556 72290 20996 11179 SOD1 SOD1 mSOD1 21 1.9 motoneuron injury and decreased neurite number and length suggesting that mSOD1 G93A microglia are functionally more toxic by releasing more nitric 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57336 17555556 72291 9939 5464 IGF1 IGF1 IGF-1 10 1.2 Additionally wild-type microglia may be more neuroprotective by secreting more IGF-1 compared to mSOD1 G93A microglia 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57337 17555556 72291 20996 11179 SOD1 SOD1 mSOD1 13 1.9 may be more neuroprotective by secreting more IGF-1 compared to mSOD1 G93A microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57338 17555556 72293 20996 11179 SOD1 SOD1 mSOD1 6 1.9 (2004) 2004 found that adult (60 60 days mSOD1 G93A microglia produced significantly more TNF-A and less IL-6 than 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57339 17555556 72293 22551 11892 TNF TNFA TNF-A 12 0.5 adult (60 60 days mSOD1 G93A microglia produced significantly more TNF-A and less IL-6 than wild-type microglia after LPS treatment 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57340 17555556 72293 10463 6018 IL6 IL-6 IL-6 15 1.0 days mSOD1 G93A microglia produced significantly more TNF-A and less IL-6 than wild-type microglia after LPS treatment 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57341 17555556 72293 24053 12728 VWS LPS LPS 20 0.0 significantly more TNF-A and less IL-6 than wild-type microglia after LPS treatment 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57342 17555556 72294 20996 11179 SOD1 SOD1 mSOD1 12 1.9 data is consistent with their results and showed that neonatally-derived mSOD1 G93A microglia released more nitric oxide more superoxide and less 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57343 17555556 72294 9939 5464 IGF1 IGF1 IGF-1 23 1.2 G93A microglia released more nitric oxide more superoxide and less IGF-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57344 17555556 72295 20996 11179 SOD1 SOD1 mSOD1 7 1.9 In addition we further provide evidence that mSOD1 G93A microglia are more neurotoxic than wild-type microglia in microglia/motoneuron 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57345 17555556 72298 14535 7873 NOS2A iNOS iNOS 33 2.8 a heightened sensitivity to LPS as demonstrated by superinduction of iNOS and activation of mitogen-activated protein kinase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57346 17555556 72298 24053 12728 VWS LPS LPS 13 0.0 microglia derived from mutant presenilin-1 mice were more sensitive to LPS treatment than wild-type microglia microglia expressing mutant presenilin-1 exhibited a 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57347 17555556 72298 24053 12728 VWS LPS LPS 27 0.0 microglia microglia expressing mutant presenilin-1 exhibited a heightened sensitivity to LPS as demonstrated by superinduction of iNOS and activation of mitogen-activated 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57348 17555556 72300 21160 11241 SPI1 PU.1 PU.1 13 1.0 the effects of wild-type microglia in vivo we recently used PU.1 knockout (PU.1 PU.1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 mice that at birth 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57349 17555556 72300 21160 11241 SPI1 PU.1 PU.1 15 1.0 wild-type microglia in vivo we recently used PU.1 knockout (PU.1 PU.1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 mice that at birth lack macrophages neutrophils 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57350 17555556 72301 21160 11241 SPI1 PU.1 PU.1 8 1.0 We demonstrated that following bone marrow transplantation of PU.1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 mice expressing the G93A form of mSOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57351 17555556 72301 20996 11179 SOD1 SOD1 mSOD1 16 1.9 PU.1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 mice expressing the G93A form of mSOD1 (mSOD1 mSOD1 G93A /PU.1 PU.1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 wild-type microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57352 17555556 72301 20996 11179 SOD1 SOD1 mSOD1 17 1.9 _amp_#8722 _amp_#8722 mice expressing the G93A form of mSOD1 (mSOD1 mSOD1 G93A /PU.1 PU.1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 wild-type microglia significantly slowed 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57353 17555556 72301 21160 11241 SPI1 PU.1 PU.1 19 1.0 expressing the G93A form of mSOD1 (mSOD1 mSOD1 G93A /PU.1 PU.1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 wild-type microglia significantly slowed motoneuron loss and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57354 17555556 72301 20996 11179 SOD1 SOD1 mSOD1 39 1.9 prolonged disease duration and survival when compared with mice receiving mSOD1 G93A microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57355 17555556 72304 20996 11179 SOD1 SOD1 SOD1 7 1.9 (2006) 2006 used transgenic mice with a different SOD1 mutation mSOD1 G37R and a different technique to reduce the 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57356 17555556 72304 20996 11179 SOD1 SOD1 mSOD1 9 1.9 (2006) 2006 used transgenic mice with a different SOD1 mutation mSOD1 G37R and a different technique to reduce the expression of 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57357 17555556 72304 20996 11179 SOD1 SOD1 mSOD1 21 1.9 G37R and a different technique to reduce the expression of mSOD1 G37R (i.e i.e the Cre-Lox system to reach a similar 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57358 17555556 72304 20996 11179 SOD1 SOD1 mSOD1 37 1.9 to reach a similar conclusion namely that the reduction of mSOD1 in microglia prolonged disease duration and survival 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57359 17555556 72305 20996 11179 SOD1 SOD1 mSOD1 16 1.9 of disease may be more related to the expression of mSOD1 in motoneurons while in accord with our data duration of 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57360 17555556 72305 20996 11179 SOD1 SOD1 mSOD1 34 1.9 data duration of disease may be related to expression of mSOD1 in microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57361 17555556 72306 20996 11179 SOD1 SOD1 mSOD1 42 1.9 increase in a neurotrophic molecule from wild-type microglia relative to mSOD1 G93A microglia suggesting potential mechanisms for how wild-type microglia either 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57362 17555556 72306 20996 11179 SOD1 SOD1 mSOD1 60 1.9 wild-type microglia either by the reduction or the elimination of mSOD1 expression are less toxic in vivo 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57363 17555556 72307 20996 11179 SOD1 SOD1 mSOD1 9 1.9 Because wt-hSOD1 is another control for the neurotoxicity of mSOD1 G93A we compared the relative neurotoxicity of wt-hSOD1 expressing microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57364 17555556 72307 20996 11179 SOD1 SOD1 mSOD1 24 1.9 the relative neurotoxicity of wt-hSOD1 expressing microglia to that of mSOD1 G93A expressing microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57365 17555556 72308 20996 11179 SOD1 SOD1 mSOD1 23 1.9 extent of neurotoxicity was significantly less than that mediated by mSOD1 G93A microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57366 17555556 72309 20996 11179 SOD1 SOD1 mSOD1 2 1.9 Furthermore unlike mSOD1 G93A microglia wt-hSOD1 microglia produce similar amounts of nitric oxide 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57367 17555556 72309 9939 5464 IGF1 IGF1 IGF-1 15 1.2 wt-hSOD1 microglia produce similar amounts of nitric oxide superoxide and IGF-1 compared with their wild-type littermates 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57368 17555556 72313 20996 11179 SOD1 SOD1 mSOD1 3 1.9 When backcrossed into mSOD1 mice the disease progresses more rapidly in these double transgenic 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57369 17555556 72318 20996 11179 SOD1 SOD1 mSOD1 3 1.9 The reasons that mSOD1 G93A microglia are more activated and more responsive to LPS 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57370 17555556 72318 24053 12728 VWS LPS LPS 13 0.0 mSOD1 G93A microglia are more activated and more responsive to LPS than wild-type microglia still require investigation 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57371 17555556 72320 20996 11179 SOD1 SOD1 mSOD1 2 1.9 Firstly over-expressing mSOD1 may impair the self-feedback systems in microglia and regulate activation 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57372 17555556 72321 4413 1984 CISH SOCS SOCS 7 1.6 For example the suppressor of cytokine signaling (SOCS) SOCS group of proteins has been implicated in a negative feedback 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57373 17555556 72322 20987 19383 SOCS1 SOCS-1 SOCS-1 0 2.5 SOCS-1 and SOCS-3 are critical factors down-regulating the toxic effects of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57374 17555556 72322 20991 19391 SOCS3 SOCS-3 SOCS-3 0 2.5 SOCS-1 and SOCS-3 are critical factors down-regulating the toxic effects of 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57375 17555556 72322 20991 19391 SOCS3 SOCS-3 SOCS-3 2 2.5 SOCS-1 and SOCS-3 are critical factors down-regulating the toxic effects of LPS ( 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57376 17555556 72322 20996 11179 SOD1 SOD1 mSOD1 31 1.9 al 2002 and may well influence the toxic effects of mSOD1 microglia 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57377 17555556 72322 24053 12728 VWS LPS LPS 11 0.0 and SOCS-3 are critical factors down-regulating the toxic effects of LPS ( Berlato et al 2002 Nakagawa et al 2002 and 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57378 17555556 72323 20996 11179 SOD1 SOD1 mSOD1 1 1.9 Secondly mSOD1 may lead to microglial activation either by directly stimulating the 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57379 17555556 72324 20996 11179 SOD1 ALS ALS 9 1.9 A recent study showed a novel pathogenic mechanism for ALS based on chromogranin-mediated secretion of misfolded mutant SOD1 but not 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00146837970366485<>ScoreDetail__5468|IGFALS|0.000620334567109861__11179|SOD1|0.00146837970366485__ 0 0 0 0 0 57380 17555556 72324 20996 11179 SOD1 SOD1 SOD1 17 1.9 mechanism for ALS based on chromogranin-mediated secretion of misfolded mutant SOD1 but not wild-type SOD1 from cells and extracellular mutant SOD1 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57381 17555556 72324 20996 11179 SOD1 SOD1 SOD1 21 1.9 on chromogranin-mediated secretion of misfolded mutant SOD1 but not wild-type SOD1 from cells and extracellular mutant SOD1 could trigger microgliosis ( 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57382 17555556 72324 20996 11179 SOD1 SOD1 SOD1 27 1.9 SOD1 but not wild-type SOD1 from cells and extracellular mutant SOD1 could trigger microgliosis ( Urushitani et al 2005 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57383 17555556 72325 20996 11179 SOD1 SOD1 mSOD1 7 1.9 In summary we demonstrate that microglia from mSOD1 G93A transgenic mice are more activated and more responsive to 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57384 17555556 72325 9939 5464 IGF1 IGF1 IGF-1 33 1.2 mice by producing more nitrite oxide and superoxide and less IGF-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57385 17555556 72325 24053 12728 VWS LPS LPS 18 0.0 G93A transgenic mice are more activated and more responsive to LPS than microglia from wild-type mice by producing more nitrite oxide 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 57386 17555556 72326 20996 11179 SOD1 SOD1 mSOD1 4 1.9 Relative to wild-type microglia mSOD1 G93A microglia may gain modulatory mechanisms that enhance microglial activation 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 57387 17555556 72327 20996 11179 SOD1 SOD1 mSOD1 14 1.9 neurotoxic substances and the decreased production of neurotrophic molecules by mSOD1 G93A microglia may enhance neurotoxicity or lessen neuroprotection 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58368 17569578 73491 17031 9232 PPARA PPAR PPARs 7 2.8 The biology of peroxisome proliferator activated receptors (PPARs) PPARs in physiological and pathophysiological processes has been primarily studied in 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58369 17569578 73492 17031 9232 PPARA PPAR PPARs 5 2.8 Recently it became clear that PPARs play an important role for the pathogenesis of various disorders 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58370 17569578 73493 17031 9232 PPARA PPAR PPARs 5 2.8 The finding that activation of PPARs and in particular the PPAR_amp_#x3b3 isoform suppresses inflammation in peripherial 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58371 17569578 73494 17031 9232 PPARA PPAR PPAR 3 3.0 Activation of all PPAR isoforms but especially of PPAR_amp_#x3b3 has been found to be 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58372 17569578 73496 926 620 APP amyloid amyloid 19 1.0 in response to neurodegeneration and to extracellular deposition of _amp_#x3b2 -amyloid peptides 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 58373 17569578 73499 17031 9232 PPARA PPAR PPAR 3 3.0 The ability of PPAR agonists to elicit anti-amyloidogenic anti-inflammatory and insulin sensitizing effects may 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58374 17569578 73500 17031 9232 PPARA PPAR PPAR 6 3.0 A number of clinical trials employing PPAR agonists have yielded promising results and further trials are in 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58375 17569578 73503 17031 9232 PPARA PPAR PPARs 8 2.8 Less is known about the physiological role of PPARs for brain development maintenance and function 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58376 17569578 73504 17031 9232 PPARA PPAR PPARs 9 2.8 Lesions from transgenic mouse models however provide evidence that PPARs may play pivotal roles for CNS development and function 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58377 17569578 73506 17031 9232 PPARA PPAR PPARs 3 2.8 Physiological function of PPARs in the brain 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58378 17569578 73507 17031 9232 PPARA PPAR PPARs 5 2.8 The peroxisome proliferator activated receptors (PPARs) PPARs are ligand-inducible transcription factors which belong to the superfamily of 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58379 17569578 73508 17031 9232 PPARA PPAR PPARs 21 2.8 and retinoid receptors it is thought that the ability of PPARs to bind to a ligand was acquired during metazoan evolution 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58380 17569578 73509 17031 9232 PPARA PPAR PPAR 2 3.0 Three different PPAR isotypes (PPAR_amp_#x3b1;, PPAR_amp_#x3b1 PPAR_amp_#x3b2 also called _amp_#x3b4 and PPAR_amp_#x3b3 have 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58381 17569578 73511 17031 9232 PPARA PPAR PPARs 0 2.8 PPARs are involved in several aspects of tissue differentiation and rodent 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58382 17569578 73512 17031 9232 PPARA PPAR PPAR 12 3.0 PPAR_amp_#x3b1 _amp_#x3b2;/_amp_#x3b4; _amp_#x3b2 _amp_#x3b4 and _amp_#x3b3 developed from a common PPAR gene with broad ligand-binding specificity itself derived from the ancestral 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58383 17569578 73513 17031 9232 PPARA PPAR PPARs 0 2.8 PPARs regulate gene expression through multiple mechanisms and function as obligate 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58384 17569578 73514 17031 9232 PPARA PPAR PPARs 7 2.8 Like the other members of the superfamily PPARs are composed of four domains 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58385 17569578 73517 17031 9232 PPARA PPAR PPARs 9 2.8 E/F E F domain is responsible for the dimerization of PPARs with RXRs and the ligand-dependent transactivation function of the receptor 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58386 17569578 73518 17031 9232 PPARA PPAR PPARs 0 2.8 PPARs act to stimulate gene expression through binding to conserved DNA 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58387 17569578 73522 17031 9232 PPARA PPAR PPARs 0 2.8 PPARs also act to inhibit proinflammatory gene expression and do so 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58388 17569578 73529 17031 9232 PPARA PPAR PPARs 1 2.8 The PPARs act principally as lipid sensors and regulate whole body metabolism 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58389 17569578 73541 17031 9232 PPARA PPAR PPARs 2 2.8 Binding of PPARs to their specific ligands is leading to conformational changes which 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58390 17569578 73542 17031 9232 PPARA PPAR PPARs 3 2.8 Even though all PPARs can be attributed to a common ancestral nuclear receptor each 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58391 17569578 73542 17031 9232 PPARA PPAR PPAR 14 3.0 can be attributed to a common ancestral nuclear receptor each PPAR isotype has its own properties with regard to ligand binding 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58392 17569578 73548 8612 4458 GPI PGI PGI 5 0.3 PPAR_amp_#x3b2;/_amp_#x3b4; PPAR_amp_#x3b2 _amp_#x3b4 agonists include the prostacyclin PGI 2 and synthetic agents including GW0742 GW501516 and GW7842 1 JUMiner_v2.2 1 2 prostacyclin 0 2 1044 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:1044|BGN|0.000683936789173194<>ScoreDetail__1044|BGN|0.000683936789173194__4458|GPI|0.000553558943116586__ 0 0 0 0 0 58393 17569578 73549 17031 9232 PPARA PPAR PPAR 2 3.0 All three PPAR isotypes can be activated by polyunsaturated fatty acids with different 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58394 17569578 73559 17031 9232 PPARA PPAR PPARs 9 2.8 There is less known about the expression of the PPARs during human development 6 122 and 126 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58395 17569578 73570 17031 9232 PPARA PPAR PPAR 2 3.0 All three PPAR isotypes are co-expressed in the nervous system during late rat 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58396 17569578 73571 17031 9232 PPARA PPAR PPAR 5 3.0 The expression of the three PPAR isotypes peaks in the rat CNS between day 13.5 and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58397 17569578 73574 17031 9232 PPARA PPAR PPARs 17 2.8 is isotype specific and regulated during development suggests that the PPARs may play a role during the formation of the CNS 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58398 17569578 73580 17031 9232 PPARA PPAR PPARs 1 2.8 All PPARs including PPAR_amp_#x3b3 have been described in the adult and developing 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58399 17569578 73581 17031 9232 PPARA PPAR PPAR 6 3.0 Furthermore it has been suggested that PPAR activation in neurons may directly influence neuron cell viability and 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58400 17569578 73583 17031 9232 PPARA PPAR PPARs 3 2.8 The localization of PPARs has also been investigated in purified cultures of neural cells 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58401 17569578 73586 17031 9232 PPARA PPAR PPAR 4 3.0 Astrocytes possess all three PPAR isotypes although to different degrees depending on the brain area 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58402 17569578 73587 17031 9232 PPARA PPAR PPARs 3 2.8 The role of PPARs in the CNS is mainly been related to lipid metabolism 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58403 17569578 73591 17031 9232 PPARA PPAR PPARs 2 2.8 Role of PPARs in neuro-immunological disease 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58404 17569578 73596 10463 6018 IL6 IL-6 IL-6 12 1.9 TNF_amp_#x3b1 interferon _amp_#x3b3;_amp_#xa0;(IFN_amp_#x3b3;), _amp_#x3b3 _amp_#xa0 IFN_amp_#x3b3 and interleukin 6 (IL-6) IL-6 are regularly found in multiple sclerosis brain lesions and in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58405 17569578 73600 13374 7197 MOG MOG MOG 18 1.9 demonstrated in the myelin oligodendrocyte glycoprotein peptide 35_amp_#x2013 55 (MOG MOG 35_amp_#x2013 55 induced EAE model that activation of PPAR_amp_#x3b3 limits 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58406 17569578 73603 10480 5962 IL10 IL-10 IL-10 31 1.3 PPAR_amp_#x3b3 ligand 15d-PGJ 2 inhibited T-cell proliferation and suppressed IFN_amp_#x3b3 IL-10 and IL-4 generation by activated lymphocytes 53 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58407 17569578 73603 10458 6014 IL4 IL-4 IL-4 33 1.3 15d-PGJ 2 inhibited T-cell proliferation and suppressed IFN_amp_#x3b3 IL-10 and IL-4 generation by activated lymphocytes 53 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58408 17569578 73606 13374 7197 MOG MOG MOG 14 1.9 then the first to show that oral pioglitzone treatment of MOG 35_amp_#x2013 55 -immunized mice not only reduced brain inflammation and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58409 17569578 73608 13374 7197 MOG MOG MOG 22 1.9 as pioglitazone or GW7845 within the first two weeks of MOG 35_amp_#x2013 55 -induced EAE a phenomenon that may be explained 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58410 17569578 73609 13374 7197 MOG MOG MOG 17 1.9 suppressed the IFN_amp_#x3b3 secretion of splenic T cells stimulated by MOG 35_amp_#x2013 55 in vitro 61 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58411 17569578 73612 3758 10618 CCL2 MCP1 MCP1 13 1.3 been shown to reduce the expression of the monocytic chemoattractant MCP1 95 IP-10 (CXCL3), CXCL3 MIG and I-TAC 117 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58412 17569578 73612 5198 10637 CXCL10 IP-10 IP-10 16 1.3 to reduce the expression of the monocytic chemoattractant MCP1 95 IP-10 (CXCL3), CXCL3 MIG and I-TAC 117 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58413 17569578 73612 5194 4604 CXCL3 CXCL3 CXCL3 17 0.3 the expression of the monocytic chemoattractant MCP1 95 IP-10 (CXCL3), CXCL3 MIG and I-TAC 117 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58414 17569578 73612 5197 7098 CXCL9 MIG MIG 18 0.3 expression of the monocytic chemoattractant MCP1 95 IP-10 (CXCL3), CXCL3 MIG and I-TAC 117 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58415 17569578 73612 5199 10638 CXCL11 I-TAC I-TAC 20 1.3 the monocytic chemoattractant MCP1 95 IP-10 (CXCL3), CXCL3 MIG and I-TAC 117 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58416 17569578 73613 3766 10632 CCL5 RANTES RANTES 36 1.3 pioglitazone a decrease in the mRNA levels for MIP1_amp_#x3b1 and RANTES both key chemokines in the MOG 35_amp_#x2013 55 induced EAE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58417 17569578 73613 13374 7197 MOG MOG MOG 42 1.9 levels for MIP1_amp_#x3b1 and RANTES both key chemokines in the MOG 35_amp_#x2013 55 induced EAE model has been observed 61 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58418 17569578 73617 13374 7197 MOG MOG MOG 34 1.9 an increase in T cell proliferation and Th1 response upon MOG peptide stimulation when compared to PPAR_amp_#x3b3 wild type littermate controls 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58419 17569578 73617 22088 15934 TH1L TH1 Th1 31 0.0 cord sections and an increase in T cell proliferation and Th1 response upon MOG peptide stimulation when compared to PPAR_amp_#x3b3 wild 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58420 17569578 73621 13374 7197 MOG MOG MOG 26 1.9 PPAR_amp_#x3b2;/_amp_#x3b4; PPAR_amp_#x3b2 _amp_#x3b4 agonist GW0742 exerted beneficial effects in the MOG 35_amp_#x2013 55 induced EAE model 136 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58421 17569578 73629 10452 6001 IL2 IL-2 IL-2 14 1.3 by T lymphocytes and its activation results in suppression of IL-2 production and proliferation 44 and 116 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58422 17569578 73631 13374 7197 MOG MOG MOG 13 1.9 PPAR_amp_#x3b1 agonist reduced the IgG response in mice immunized with MOG 35_amp_#x2013 55 and complete Freund_amp_#x2019 s adjuvant 43 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58423 17569578 73632 10463 6018 IL6 IL-6 IL-6 18 1.9 treated mice showed an impaired generation of IFN_amp_#x3b3 TNF_amp_#x3b1 and IL-6 in response to MOG peptide in vitro restimulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58424 17569578 73632 13374 7197 MOG MOG MOG 22 1.9 impaired generation of IFN_amp_#x3b3 TNF_amp_#x3b1 and IL-6 in response to MOG peptide in vitro restimulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58425 17569578 73634 10458 6014 IL4 IL-4 Il-4 8 1.3 The authors showed that gemfibrozil and ciprofibrate induced Il-4 production in murine and human lymphocytes while IFN_amp_#x3b3 production was 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58426 17569578 73635 12436 6925 MBP MBP MBP 10 0.3 In addition oral treatment of mice with gemfibrozil protected from MBP induced EAE and strongly reduced CD4 lymphocyte and macrophage infiltration 1 JUMiner_v2.2 1 0 0 2 6925 TotalCon:3<>6925|MBP|4155|Complete__9362|PRG2|5553|Complete__6922|MBL2|4153|Complete__<>AvaiableGeneRif=3<>BEST:6925|MBP|0.000624054615901057<>ScoreDetail__6925|MBP|0.000624054615901057__9362|PRG2|0.000502378121284186__6922|MBL2|0.000453410089881275__ 0 0 0 0 0 58427 17569578 73635 3865 1678 CD4 CD4 CD4 16 0.6 with gemfibrozil protected from MBP induced EAE and strongly reduced CD4 lymphocyte and macrophage infiltration into the CNS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58428 17569578 73639 11668 6518 LBR PHA PHA 24 0.0 on human T-leukemia cells (Jurkat Jurkat cells and phytohemagglutinin (PHA)-stimulated PHA -stimulated PBMCs derived from 21 MS patients and 12 healthy 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58429 17569578 73640 11668 6518 LBR PHA PHA-induced 6 0.0 In this study all drugs suppressed PHA-induced T-cell proliferation by 40_amp_#x2013 50% and secretion of IFN_amp_#x3b3 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58430 17569578 73648 11668 6518 LBR PHA PHA-induced 7 0.0 Importantly long-term oral pioglitazone treatment prevented the PHA-induced loss of PPAR_amp_#x3b3 expression in PBMCs from diabetic patients demonstrating 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58431 17569578 73656 17031 9232 PPARA PPAR PPAR 10 3.0 The aforementioned in vitro and in vivo experiments suggest that PPAR activation may be used as a new therapeutic avenue in 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58432 17569578 73660 17031 9232 PPARA PPAR PPARs 2 2.8 Role of PPARs in neurodegenerative disorders 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58433 17569578 73676 14535 7873 NOS2A iNOS iNOS 9 1.0 In addition neuronal expression of inflammatory enzyme systems including iNOS have been described in AD 77 105 and 165 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58434 17569578 73677 14535 7873 NOS2A iNOS iNOS 4 1.0 The experimental expression of iNOS in neurons resulted in time dependent neuronal cell death which 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58435 17569578 73678 14535 7873 NOS2A iNOS iNOS 9 1.0 PPAR_amp_#x3b3 activation in microglial cells suppressed inflammatory cytokine expression iNOS expression and NO production and inhibition of COX2 and subsequent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58436 17569578 73678 17610 9605 PTGS2 COX2 COX2 17 2.5 cytokine expression iNOS expression and NO production and inhibition of COX2 and subsequent generation of immunostimulated prostanoid synthesis 38 1 JUMiner_v2.2 1 0 0 2 9605 TotalCon:2<>7421|MT-CO2|4513|Complete__9605|PTGS2|5743|Complete__<>AvaiableGeneRif=2<>BEST:9605|PTGS2|0.000709346637997174<>ScoreDetail__7421|MT-CO2|0.000413457600860465__9605|PTGS2|0.000709346637997174__ 0 0 0 0 0 58437 17569578 73679 7683 3796 FOS AP-1 AP-1 33 1.3 transcription factor NF_amp_#x3ba B (and and to a lesser extent AP-1 and STATs 46 1 JUMiner_v2.2 1 0 0 2 6204 TotalCon:5<>3796|FOS|2353|Complete__3797|FOSB|2354|Complete__6204|JUN|3725|Complete__6205|JUNB|3726|Complete__6206|JUND|3727|Complete__<>AvaiableGeneRif=5<>BEST:6204|JUN|0.0006507927152134<>ScoreDetail__3796|FOS|0.000611685922350199__3797|FOSB|0.000528335192517499__6205|JUNB|0.000641560331517206__6204|JUN|0.0006507927152134__6206|JUND|0.000620439813636721__ 0 0 0 0 0 58438 17569578 73679 21414 11362 STAT1 STAT STATs 35 0.3 NF_amp_#x3ba B (and and to a lesser extent AP-1 and STATs 46 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58439 17569578 73683 926 620 APP APP APP 17 0.3 been investigated in animal models of AD that overexpress human APP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58440 17569578 73689 926 620 APP amyloid amyloid 9 1.0 The finding that PPAR_amp_#x3b3 agonists elicited a reduction in amyloid pathology in animal models of the disease may be the 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 58441 17569578 73691 1490 933 BACE1 BACE1 BACE1 17 0.5 was the result of inhibition of beta secretease 1 (BACE1) BACE1 expression through a PPAR_amp_#x3b3 -dependent suppression of the BACE1 gene 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58442 17569578 73691 1490 933 BACE1 BACE1 BACE1 25 0.5 (BACE1) BACE1 expression through a PPAR_amp_#x3b3 -dependent suppression of the BACE1 gene promoter 149 and 150 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58443 17569578 73692 926 620 APP APP APP 10 0.3 Similarly Heneka et al found that oral pioglitazone treatment of APP transgenic mice reduced BACE1 transcription and expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58444 17569578 73692 1490 933 BACE1 BACE1 BACE1 14 0.5 found that oral pioglitazone treatment of APP transgenic mice reduced BACE1 transcription and expression 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58445 17569578 73693 926 620 APP APP APP 12 0.3 of independent studies found that PPAR_amp_#x3b3 activation regulated both cellular APP levels and A_amp_#x3b2 production by stimulating the ubiquitin-mediated degradation of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58446 17569578 73693 926 620 APP APP APP 23 0.3 levels and A_amp_#x3b2 production by stimulating the ubiquitin-mediated degradation of APP 45 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58447 17569578 73702 9847 5381 IDE IDE IDE 18 1.3 an increase in the levels of insulin degrading enzyme (IDE) IDE in rosiglitazone treated transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58448 17569578 73703 9847 5381 IDE IDE IDE 0 1.3 IDE acts to proteolytically degrade amyloid peptides and has been genetically 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58449 17569578 73703 926 620 APP amyloid amyloid 5 1.0 IDE acts to proteolytically degrade amyloid peptides and has been genetically linked to AD 139 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 58450 17569578 73722 912 613 APOE APOE ApoE 13 0.0 the differential effects of rosiglitazone in individuals depending on their ApoE genotype is unexplained 14 JUMiner_v2.2 1 1 apoe; 0 0 0 0 0 0 0 0 58451 17569578 73731 14535 7873 NOS2A iNOS iNOS 11 1.0 studies suggested that neuroinflammatory changes accompanied by microglial and astroglial iNOS expression may play a pivotal role in PD 79 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58452 17569578 73732 14535 7873 NOS2A iNOS iNOS 9 1.0 Since PPAR_amp_#x3b3 activation results in a profound suppression of iNOS in peripheral macrophages 37 and 142 as well as in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58453 17569578 73737 14535 7873 NOS2A iNOS iNOS-positive 11 1.0 decreased microglial and astrocyte activation and reduced the number of iNOS-positive cells in both the striatum and SNpc 19 and 47 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 58454 17569578 73738 14535 7873 NOS2A iNOS iNOS 2 1.0 In part iNOS suppression in MPTP treated mice may have been achieved by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58455 17569578 73742 13434 7225 MPZ MPP MPP 10 0.3 colleagues demonstrated that PPAR_amp_#x3b2;/_amp_#x3b4;_amp_#xa0;agonist PPAR_amp_#x3b2 _amp_#x3b4 _amp_#xa0 agonist treatment of MPP stimulated neuroblastoma cells exerted neuroprotective effects 85 1 JUMiner_v2.2 1 2 UserEdit 0 2 7214 TotalCon:2<>7214|MPHOSPH6|10200|Complete__7225|MPZ|4359|Complete__<>AvaiableGeneRif=2<>BEST:7214|MPHOSPH6|0.000624256837098692<>ScoreDetail__7214|MPHOSPH6|0.000624256837098692__7225|MPZ|0.000474578928800094__ 1 1 0 0 0 58456 17569578 73748 20996 11179 SOD1 ALS ALS 3 0.5 Amyotrophic lateral sclerosis (ALS) ALS represents a fatal neurodegenerative disorder characterized by progressive death of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000909962863677726<>ScoreDetail__5468|IGFALS|0.00074992500749925__11179|SOD1|0.000909962863677726__ 0 0 0 0 0 58457 17569578 73749 20996 11179 SOD1 ALS ALS 28 0.5 treatment strategies are being evaluated in transgenic mouse models of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000909962863677726<>ScoreDetail__5468|IGFALS|0.00074992500749925__11179|SOD1|0.000909962863677726__ 0 0 0 0 0 58458 17569578 73750 20996 11179 SOD1 ALS ALS 27 0.5 tested whether SOD1-G93A transgenic mice an established mouse model of ALS benefit from oral treatment with the PPAR_amp_#x3b3 agonist pioglitazone 92 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000909962863677726<>ScoreDetail__5468|IGFALS|0.00074992500749925__11179|SOD1|0.000909962863677726__ 0 0 0 0 0 58459 17569578 73756 17610 9605 PTGS2 COX-2 COX-2 20 2.8 pioglitazone treated SOD1-G93A mice as were the protein levels of COX-2 and iNOS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58460 17569578 73756 14535 7873 NOS2A iNOS iNOS 22 1.0 SOD1-G93A mice as were the protein levels of COX-2 and iNOS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58461 17569578 73758 20996 11179 SOD1 SOD1 SOD1 27 0.5 whereas both the mRNA and protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected 154 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58462 17569578 73758 20996 11179 SOD1 SOD1 SOD1 32 0.5 protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected 154 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58463 17569578 73759 20996 11179 SOD1 ALS ALS 12 0.5 underlying mechanisms are not fully understood both studies suggest that ALS patients may benefit from treatment with this PPAR_amp_#x3b3 agonist 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000909962863677726<>ScoreDetail__5468|IGFALS|0.00074992500749925__11179|SOD1|0.000909962863677726__ 0 0 0 0 0 58464 17569578 73760 20996 11179 SOD1 ALS ALS 25 0.5 a first clinical trial (GERPALS, GERPALS German pioglitazone study in ALS which will start to enroll patients late 2007 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000909962863677726<>ScoreDetail__5468|IGFALS|0.00074992500749925__11179|SOD1|0.000909962863677726__ 0 0 0 0 0 58465 17569578 73762 17031 9232 PPARA PPAR PPARs 0 2.8 PPARs in cerebral ischemia 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58466 17569578 73766 14535 7873 NOS2A iNOS iNOS 26 1.0 chemokine expression as well as elevated expression of adhesion molecules iNOS COX2 and other inflammatory mediators which act to exacerbate the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58467 17569578 73766 17610 9605 PTGS2 COX2 COX2 27 2.5 expression as well as elevated expression of adhesion molecules iNOS COX2 and other inflammatory mediators which act to exacerbate the tissue 1 JUMiner_v2.2 1 0 0 2 9605 TotalCon:2<>7421|MT-CO2|4513|Complete__9605|PTGS2|5743|Complete__<>AvaiableGeneRif=2<>BEST:9605|PTGS2|0.000709346637997174<>ScoreDetail__7421|MT-CO2|0.000413457600860465__9605|PTGS2|0.000709346637997174__ 0 0 0 0 0 58468 17569578 73772 14535 7873 NOS2A iNOS iNOS 20 1.0 infiltration of peripheral leukocytes diminished microglial activation and reduction of iNOS COX2 and cytokine expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58469 17569578 73772 17610 9605 PTGS2 COX2 COX2 21 2.5 of peripheral leukocytes diminished microglial activation and reduction of iNOS COX2 and cytokine expression 1 JUMiner_v2.2 1 0 0 2 9605 TotalCon:2<>7421|MT-CO2|4513|Complete__9605|PTGS2|5743|Complete__<>AvaiableGeneRif=2<>BEST:9605|PTGS2|0.000709346637997174<>ScoreDetail__7421|MT-CO2|0.000413457600860465__9605|PTGS2|0.000709346637997174__ 0 0 0 0 0 58470 17569578 73777 17031 9232 PPARA PPAR PPAR 6 3.0 The principal focus of studies of PPAR agonists has been on agonists of the PPAR_amp_#x3b3 isoform however 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58471 17569578 73781 17031 9232 PPARA PPAR PPAR 9 3.0 Likewise Arsenijevic and colleagues have explored the role of PPAR _amp_#x3b2;/_amp_#x3b4; _amp_#x3b2 _amp_#x3b4 in murine stroke and found that PPAR 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58472 17569578 73781 17031 9232 PPARA PPAR PPAR 17 3.0 PPAR _amp_#x3b2;/_amp_#x3b4; _amp_#x3b2 _amp_#x3b4 in murine stroke and found that PPAR _amp_#x3b2;/_amp_#x3b4; _amp_#x3b2 _amp_#x3b4 null mice exhibited significantly greater infarct sizes 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58473 17569578 73787 17031 9232 PPARA PPAR PPARs 26 2.8 risk for ischemic stroke 103 further supporting the importance of PPARs in cerebral ischemia 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58474 17569578 73789 17031 9232 PPARA PPAR PPARs 0 2.8 PPARs and tumors of the nervous system 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58475 17569578 73797 17031 9232 PPARA PPAR PPARs 3 2.8 All isoforms of PPARs are expressed in the brain 133 and 142 as well 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58476 17569578 73799 17031 9232 PPARA PPAR PPARs 13 2.8 in other neoplastic disease several natural and synthetic ligands of PPARs have been tested for their efficacy in the treatment of 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58477 17569578 73804 19623 10722 SELPLG CLA CLA 5 0.3 Treatment with conjugated linoleic acid (CLA) CLA inhibited growth in human ADF glioblastoma cells 33 and 114 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 58478 17569578 73804 6176 15750 DSTN ADF ADF 10 0.0 with conjugated linoleic acid (CLA) CLA inhibited growth in human ADF glioblastoma cells 33 and 114 and this was associated with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58479 17569578 73805 19623 10722 SELPLG CLA CLA 7 0.3 Cimini and others 33 also found that CLA and the PPAR_amp_#x3b3 agonist GW347845X induced apoptosis in ADF cells 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 58480 17569578 73805 6176 15750 DSTN ADF ADF 16 0.0 that CLA and the PPAR_amp_#x3b3 agonist GW347845X induced apoptosis in ADF cells suggesting that this effect was mediated by PPAR_amp_#x3b3 activation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58481 17569578 73806 19623 10722 SELPLG CLA CLA 16 0.3 finding that the PPAR_amp_#x3b3 antagonist GW259662 completely prevented both the CLA and GW347854X-induced effects on cell growth and apoptosis 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 58482 17569578 73807 13323 7166 MMP2 MMP2 MMP2 22 0.3 was associated with a decrease in matrix metalloproteinase 2 (MMP2) MMP2 levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58483 17569578 73809 18723 10261 ROS1 ROS ROS 10 0.0 and co-workers reported that generation of reactive oxygen species (ROS) ROS was likely to be responsible for glitazone-induced glial cell death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58484 17569578 73812 17031 9232 PPARA PPAR PPAR 8 3.0 Tetradecylthioacetic acid (TTA), TTA a saturated fatty acid and PPAR ligand inhibited growth of BT4Cn rat glioma cells at increased 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58485 17569578 73819 13262 7107 MKI67 Ki-67 Ki-67 11 1.6 proliferation in rat glioma cells was inhibited as measured by Ki-67 expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58486 17569578 73824 13327 7176 MMP9 MMP9 MMP9 14 0.3 decreased tumor invasion in vivo that were correlated with reduced MMP9 levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58487 17569578 73828 17031 9232 PPARA PPAR PPAR 0 3.0 PPAR agonists have also been shown to exhibit effects on tumor 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58488 17569578 73828 17031 9232 PPARA PPAR PPAR-independent 13 2.5 also been shown to exhibit effects on tumor biology through PPAR-independent mechanisms 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58489 17569578 73829 17031 9232 PPARA PPAR PPAR-independent 19 2.5 growth of T98G human glioblastoma cells and induced apoptosis through PPAR-independent mechanisms since their respective antagonists MK-886 and GW9662 did not 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58490 17569578 73833 22585 11925 TNFSF10 TRAIL TRAIL-induced 8 2.2 The TZD troglitazone sensitized human glioma cells to TRAIL-induced apoptosis in a process independent of PPAR_amp_#x3b3 2 and 152 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58491 17569578 73834 4255 1876 CFLAR FLIP FLIP 11 1.8 treatment led to a marked down-regulation of the anti-apoptotic proteins FLIP and survivin 152 as well Bcl-2 2 and so could 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58492 17569578 73834 1576 990 BCL2 Bcl-2 Bcl-2 17 1.0 of the anti-apoptotic proteins FLIP and survivin 152 as well Bcl-2 2 and so could possibly counteract the capability of tumor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58493 17569578 73835 22585 11925 TNFSF10 TRAIL TRAIL 7 2.2 Hence a combination therapy of troglitazone and TRAIL might be a promising experimental approach 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58494 17569578 73839 17031 9232 PPARA PPAR PPAR 7 3.0 The molecular understanding of antineoplastic mechanisms of PPAR agonists is still emerging 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58495 17569578 73840 17031 9232 PPARA PPAR PPARs 13 2.8 by a number of reports dealing with the influence of PPARs on glioma treatment in vitro 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58496 17569578 73842 17031 9232 PPARA PPAR PPARs 4 2.8 However the agonists of PPARs in particular the TZDs seem to be promising candidates for 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58497 17569578 73848 17031 9232 PPARA PPAR PPARs 8 2.8 Therefore most studies that assess the influence of PPARs on treatment of neuroblastoma evaluate the impact of its natural 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58498 17569578 73851 11940 6667 LPA LPA LPA 14 0.0 cell death type II or autophagy and the serum lysolipid LPA is responsible for modulating this cellular response 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58499 17569578 73852 9130 14065 HDAC9 HDAC HDAC 33 1.9 interaction with retinoblastoma protein (Rb) Rb and histone deacetylase (HDAC) HDAC 56 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58500 17569578 73853 17264 9353 PRDX2 TSA TSA 14 0.0 PGJ 2 and the histone deacetylase inhibitor trichostatin A (TSA) TSA enhanced the growth inhibition effects and is therefore proposed as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58780 17574754 74300 17610 9605 PTGS2 COX-2 COX-2 3 1.0 Induction of cyclooxygenase-2 (COX-2) COX-2 with production of prostaglandins occurs in a wide spectrum of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58781 17574754 74301 17610 9605 PTGS2 COX-2 COX-2 3 1.0 Inhibition of the COX-2 pathway and downstream production of prostaglandins protect neurons in rodent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58782 17574754 74302 17610 9605 PTGS2 COX-2 COX-2 12 1.0 investigating the functions of selected prostaglandin receptor pathways in mediating COX-2 neurotoxicity have demonstrated both toxic and paradoxically neuroprotective effects of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58783 17574754 74304 8612 4458 GPI PGI PGI 6 0.6 We find that PGD 2 PGI 2 and PGF 2_amp_#x3b1 receptors protect motor neurons in an 1 JUMiner_v2.2 1 2 prostacyclin 0 2 4458 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:4458|GPI|0.000430668045800177<>ScoreDetail__1044|BGN|0.000352631672412787__4458|GPI|0.000430668045800177__ 0 0 0 0 0 58784 17574754 74304 16457 8891 PGD PGD PGD 3 0.0 We find that PGD 2 PGI 2 and PGF 2_amp_#x3b1 receptors protect motor neurons 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58785 17574754 74304 16459 8893 PGF PGF PGF 10 0.0 We find that PGD 2 PGI 2 and PGF 2_amp_#x3b1 receptors protect motor neurons in an organotypic spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58786 17574754 74304 20996 11179 SOD1 ALS ALS 26 0.0 an organotypic spinal cord model of amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00135542706503777<>ScoreDetail__5468|IGFALS|0.000184791647417537__11179|SOD1|0.00135542706503777__ 0 0 0 0 0 58787 17574754 74305 8612 4458 GPI PGI PGI 2 0.6 In addition PGI 2 and TXA 2 receptors rescue CA1 neurons in an 1 JUMiner_v2.2 1 2 prostacyclin 0 2 4458 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:4458|GPI|0.000430668045800177<>ScoreDetail__1044|BGN|0.000352631672412787__4458|GPI|0.000430668045800177__ 0 0 0 0 0 58788 17574754 74305 3353 1368 CA1 CA1 CA1 9 0.0 In addition PGI 2 and TXA 2 receptors rescue CA1 neurons in an organotypic hippocampal model of N -methyl-d 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58789 17574754 74306 17610 9605 PTGS2 COX-2 COX-2 5 1.0 The inducible isoform of cyclooxygenase COX-2 is rapidly upregulated in vivo in hippocampal and cerebral cortical 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58790 17574754 74307 17610 9605 PTGS2 COX-2 COX-2 10 1.0 However in pathologic conditions caused by either excitotoxicity or inflammation COX-2 expression and activity are increased in neurons and glial cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58791 17574754 74308 17610 9605 PTGS2 COX-2 COX-2 2 1.0 Thus increased COX-2 activity and prostaglandin production are hallmarks of a wide range 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58792 17574754 74308 20996 11179 SOD1 ALS ALS 43 0.0 of chronic neurodegeneration that model human amyotrophic lateral sclerosis (ALS), ALS Parkinson's disease (PD), PD and Alzheimer's disease (AD; AD reviewed 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00135542706503777<>ScoreDetail__5468|IGFALS|0.000184791647417537__11179|SOD1|0.00135542706503777__ 0 0 0 0 0 58793 17574754 74309 17610 9605 PTGS2 COX-2 COX-2 3 1.0 In humans increased COX-2 and prostaglandin production have been observed in AD ALS multiple 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58794 17574754 74309 20996 11179 SOD1 ALS ALS 12 0.0 increased COX-2 and prostaglandin production have been observed in AD ALS multiple sclerosis and PD 1 10 22 and 24 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00135542706503777<>ScoreDetail__5468|IGFALS|0.000184791647417537__11179|SOD1|0.00135542706503777__ 0 0 0 0 0 58795 17574754 74310 17610 9605 PTGS2 COX-2 COX-2 1 1.0 Thus COX-2 appears to function physiologically in promoting synaptic activity and pathologically 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58796 17574754 74311 17610 9605 PTGS2 COX-2 COX-2 3 1.0 Because inhibition of COX-2 either genetically or pharmacologically decreases neuronal injury in rodent models 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58797 17574754 74311 17610 9605 PTGS2 COX-2 COX-2 28 1.0 is considerable interest in defining the downstream mechanisms by which COX-2 exerts its neurotoxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58798 17574754 74312 17610 9605 PTGS2 COX-2 COX-2 13 1.0 has been the examination of prostaglandin signaling cascades downstream of COX-2 and the identification of neurotoxic prostaglandin receptors 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58799 17574754 74313 17610 9605 PTGS2 COX-2 COX-2 17 1.0 the metabolism of arachidonic acid by COX-1 and the inducible COX-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58800 17574754 74313 17609 9604 PTGS1 COX-1 COX-1 13 0.0 signaling molecules derived from the metabolism of arachidonic acid by COX-1 and the inducible COX-2 1 JUMiner_v2.2 1 1 cox-1; 0 0 0 0 0 0 0 0 58801 17574754 74314 8612 4458 GPI PGI PGI 12 0.6 The five prostaglandins PGE 2 PGF 2_amp_#x3b1 PGD 2 PGI 2 (prostacyclin), prostacyclin and TXA 2 (thromboxane) thromboxane bind to 1 JUMiner_v2.2 1 2 prostacyclin 0 2 4458 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:4458|GPI|0.000430668045800177<>ScoreDetail__1044|BGN|0.000352631672412787__4458|GPI|0.000430668045800177__ 0 0 0 0 0 58802 17574754 74314 16459 8893 PGF PGF PGF 6 0.0 The five prostaglandins PGE 2 PGF 2_amp_#x3b1 PGD 2 PGI 2 (prostacyclin), prostacyclin and TXA 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58803 17574754 74314 16457 8891 PGD PGD PGD 9 0.0 The five prostaglandins PGE 2 PGF 2_amp_#x3b1 PGD 2 PGI 2 (prostacyclin), prostacyclin and TXA 2 (thromboxane) thromboxane 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58804 17574754 74315 17596 9593 PTGER1 EP1 EP1 20 0.3 2 EP receptor family where there are four subtypes (EP1, EP1 EP2 EP3 and EP4 and for the PGD 2 DP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58805 17574754 74315 17597 9594 PTGER2 EP2 EP2 21 0.3 EP receptor family where there are four subtypes (EP1, EP1 EP2 EP3 and EP4 and for the PGD 2 DP family 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58806 17574754 74315 17598 9595 PTGER3 EP3 EP3 22 0.3 receptor family where there are four subtypes (EP1, EP1 EP2 EP3 and EP4 and for the PGD 2 DP family where 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58807 17574754 74315 17599 9596 PTGER4 EP4 EP4 22 0.3 receptor family where there are four subtypes (EP1, EP1 EP2 EP3 and EP4 and for the PGD 2 DP family where 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58808 17574754 74315 17599 9596 PTGER4 EP4 EP4 24 0.3 where there are four subtypes (EP1, EP1 EP2 EP3 and EP4 and for the PGD 2 DP family where there are 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58809 17574754 74315 17594 9591 PTGDR DP1 DP1 37 1.1 the PGD 2 DP family where there are two receptors DP1 and DP2 (aka aka CRTH2 1 JUMiner_v2.2 1 0 0 2 9591 TotalCon:3<>30077|REEP5|7905|No_GeneRif__9591|PTGDR|5729|Complete__11749|TFDP1|7027|Complete__<>AvaiableGeneRif=2<>BEST:9591|PTGDR|0.00262777558796479<>ScoreDetail__11749|TFDP1|0.000292525961679099__9591|PTGDR|0.00262777558796479__ 0 0 0 0 0 58810 17574754 74315 8649 4502 GPR44 CRTH2 CRTH2 41 1.6 where there are two receptors DP1 and DP2 (aka aka CRTH2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58811 17574754 74315 16457 8891 PGD PGD PGD 28 0.0 subtypes (EP1, EP1 EP2 EP3 and EP4 and for the PGD 2 DP family where there are two receptors DP1 and 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58812 17574754 74315 872 583 APC DP2 DP2 37 0.3 the PGD 2 DP family where there are two receptors DP1 and DP2 (aka aka CRTH2 4 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>583|APC|324|Complete__11751|TFDP2|7029|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 58813 17574754 74315 872 583 APC DP2 DP2 39 0.2 2 DP family where there are two receptors DP1 and DP2 (aka aka CRTH2 6 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>583|APC|324|Complete__11751|TFDP2|7029|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 58814 17574754 74316 17610 9605 PTGS2 COX-2 COX-2 0 1.0 COX-2 neurotoxicity is presumed to be mediated by one or more 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58815 17574754 74318 17596 9593 PTGER1 EP1 EP1 7 0.3 A toxic effect of the PGE 2 EP1 receptor has been demonstrated in a model of focal ischemia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58816 17574754 74318 17596 9593 PTGER1 EP1 EP1 19 0.3 has been demonstrated in a model of focal ischemia where EP1 impairs the Na _amp_#x2013 Ca 2 exchange critical in maintaining 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58817 17574754 74320 17597 9594 PTGER2 EP2 EP2 8 0.3 We have previously reported that the PGE 2 EP2 receptor rescues CA1 pyramidal neurons in organotypic hippocampal cultures treated 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58818 17574754 74320 17597 9594 PTGER2 EP2 EP2 30 0.3 with NMDA or oxygen glucose deprivation 16 and both the EP2 and EP3 receptors rescue motor neurons in organotypic spinal cord 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58819 17574754 74320 17598 9595 PTGER3 EP3 EP3 30 0.3 with NMDA or oxygen glucose deprivation 16 and both the EP2 and EP3 receptors rescue motor neurons in organotypic spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58820 17574754 74320 17598 9595 PTGER3 EP3 EP3 32 0.3 or oxygen glucose deprivation 16 and both the EP2 and EP3 receptors rescue motor neurons in organotypic spinal cord slices subjected 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58821 17574754 74320 3353 1368 CA1 CA1 CA1 11 0.0 have previously reported that the PGE 2 EP2 receptor rescues CA1 pyramidal neurons in organotypic hippocampal cultures treated with NMDA or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58822 17574754 74321 17597 9594 PTGER2 EP2 EP2 3 0.3 In vivo the EP2 receptor mediates a significant protective function in models of focal 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58823 17574754 74322 17594 9591 PTGDR DP1 DP1 6 1.1 PGD 2 signaling via its DP1 receptor similarly rescues CA1 and CA3 neurons in organotypic hippocampal 1 JUMiner_v2.2 1 0 0 2 9591 TotalCon:3<>30077|REEP5|7905|No_GeneRif__9591|PTGDR|5729|Complete__11749|TFDP1|7027|Complete__<>AvaiableGeneRif=2<>BEST:9591|PTGDR|0.00262777558796479<>ScoreDetail__11749|TFDP1|0.000292525961679099__9591|PTGDR|0.00262777558796479__ 0 0 0 0 0 58824 17574754 74322 16457 8891 PGD PGD PGD 0 0.0 PGD 2 signaling via its DP1 receptor similarly rescues CA1 and 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58825 17574754 74322 3353 1368 CA1 CA1 CA1 10 0.0 PGD 2 signaling via its DP1 receptor similarly rescues CA1 and CA3 neurons in organotypic hippocampal slices treated with NMDA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58826 17574754 74322 3355 1374 CA3 CA3 CA3 10 0.0 PGD 2 signaling via its DP1 receptor similarly rescues CA1 and CA3 neurons in organotypic hippocampal slices treated with NMDA 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58827 17574754 74322 3355 1374 CA3 CA3 CA3 12 0.0 2 signaling via its DP1 receptor similarly rescues CA1 and CA3 neurons in organotypic hippocampal slices treated with NMDA 14 and 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58828 17574754 74323 17597 9594 PTGER2 EP2 EP2 1 0.3 Mechanistically EP2 and DP1 neuroprotection are dependent on intact cAMP signaling whereas 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58829 17574754 74323 17594 9591 PTGDR DP1 DP1 3 1.1 Mechanistically EP2 and DP1 neuroprotection are dependent on intact cAMP signaling whereas EP3 neuroprotection 1 JUMiner_v2.2 1 0 0 2 9591 TotalCon:3<>30077|REEP5|7905|No_GeneRif__9591|PTGDR|5729|Complete__11749|TFDP1|7027|Complete__<>AvaiableGeneRif=2<>BEST:9591|PTGDR|0.00262777558796479<>ScoreDetail__11749|TFDP1|0.000292525961679099__9591|PTGDR|0.00262777558796479__ 0 0 0 0 0 58830 17574754 74323 17598 9595 PTGER3 EP3 EP3 12 0.3 and DP1 neuroprotection are dependent on intact cAMP signaling whereas EP3 neuroprotection is associated with increased AKT phosphorylation 3 and 16 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58831 17574754 74323 543 391 AKT1 AKT AKT 18 0.3 intact cAMP signaling whereas EP3 neuroprotection is associated with increased AKT phosphorylation 3 and 16 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58832 17574754 74326 17597 9594 PTGER2 EP2 EP2 1 0.3 The EP2 receptor neuroprotective in models of glutamate toxicity enhances the inflammatory 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58833 17574754 74326 24053 12728 VWS LPS LPS 19 0.0 the inflammatory response and secondary synaptotoxicity in the lipopolysaccharide (LPS) LPS model of innate immunity 17 and 19 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58834 17574754 74327 17597 9594 PTGER2 EP2 EP2 11 0.3 a murine model of Familial Alzheimer's disease deletion of the EP2 receptor results decreased neuronal lipid peroxidation and A_amp_#x3b2 peptide load 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58835 17574754 74334 24053 12728 VWS LPS LPS 6 0.0 The following reagents were obtained commercially LPS (Calbiochem, Calbiochem San Diego CA N -methyl-d -aspartate (NMDA; NMDA 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58836 17574754 74334 16457 8891 PGD PGD PGD 32 0.0 (THA; THA Tocris Elisville MO propidium idodide (PI, PI Sigma PGD 2 BW245C fluprostenol 13 14-dehydro-15-cyclohexyl carbaprostacyclin U-46619 and 13 14-dihydro-15-keto-PGD 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58837 17574754 74337 20996 11179 SOD1 ALS ALS 12 0.0 d l -threohydroxyaspartate (THA), THA a glutamate transport inhibitor models ALS with motor neuron loss resulting from chronic glutamate toxicity 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00135542706503777<>ScoreDetail__5468|IGFALS|0.000184791647417537__11179|SOD1|0.00135542706503777__ 0 0 0 0 0 58838 17574754 74339 17594 9591 PTGDR DP1 DP1 3 1.1 PGD 2 and DP1 DP2 IP TP and FP receptor agonists were tested at 1 JUMiner_v2.2 1 0 0 2 9591 TotalCon:3<>30077|REEP5|7905|No_GeneRif__9591|PTGDR|5729|Complete__11749|TFDP1|7027|Complete__<>AvaiableGeneRif=2<>BEST:9591|PTGDR|0.00262777558796479<>ScoreDetail__11749|TFDP1|0.000292525961679099__9591|PTGDR|0.00262777558796479__ 0 0 0 0 0 58839 17574754 74339 16457 8891 PGD PGD PGD 0 0.0 PGD 2 and DP1 DP2 IP TP and FP receptor agonists 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58840 17574754 74339 872 583 APC DP2 DP2 4 0.2 PGD 2 and DP1 DP2 IP TP and FP receptor agonists were tested at 1 5 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>583|APC|324|Complete__11751|TFDP2|7029|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 58841 17574754 74345 24053 12728 VWS LPS LPS 1 0.0 For LPS experiments LPS (0.1_amp_#x2013;5 0.1_amp_#x2013 5 _amp_#x3bc;g/ml) _amp_#x3bc g ml was 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58842 17574754 74345 24053 12728 VWS LPS LPS 3 0.0 For LPS experiments LPS (0.1_amp_#x2013;5 0.1_amp_#x2013 5 _amp_#x3bc;g/ml) _amp_#x3bc g ml was administered for 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58843 17574754 74347 3353 1368 CA1 CA1 CA1 23 0.0 M NMDA and PI and incubated overnight to induce maximum CA1 neuronal loss and imaged 24 h later ( t max 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58844 17574754 74348 3353 1368 CA1 CA1 CA1 12 0.0 was assayed by quantification of mean PI fluorescence in the CA1 subregion of each hippocampal slice for t b t 24h 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58845 17574754 74353 24053 12728 VWS LPS LPS 23 0.0 spinal cord experiments between vehicle and NMDA and vehicle and LPS in organotypic hippocampal experiments 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58846 17574754 74355 17597 9594 PTGER2 EP2 EP2 11 0.3 previous studies we determined that PGE 2 signaling via its EP2 and EP3 receptors paradoxically protected motor neurons in a spinal 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58847 17574754 74355 17598 9595 PTGER3 EP3 EP3 11 0.3 previous studies we determined that PGE 2 signaling via its EP2 and EP3 receptors paradoxically protected motor neurons in a spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58848 17574754 74355 17598 9595 PTGER3 EP3 EP3 13 0.3 we determined that PGE 2 signaling via its EP2 and EP3 receptors paradoxically protected motor neurons in a spinal cord model 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58849 17574754 74357 17594 9591 PTGDR DP1 DP1 16 1.1 protected motor neurons at nM doses selective agonists of the DP1 and DP2 receptors BW245C and DK-PGD 2 respectively also significantly 1 JUMiner_v2.2 1 0 0 2 9591 TotalCon:3<>30077|REEP5|7905|No_GeneRif__9591|PTGDR|5729|Complete__11749|TFDP1|7027|Complete__<>AvaiableGeneRif=2<>BEST:9591|PTGDR|0.00262777558796479<>ScoreDetail__11749|TFDP1|0.000292525961679099__9591|PTGDR|0.00262777558796479__ 0 0 0 0 0 58850 17574754 74357 16457 8891 PGD PGD PGD 4 0.0 Co-administration of THA and PGD 2 protected motor neurons at nM doses selective agonists of 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58851 17574754 74357 872 583 APC DP2 DP2 16 0.3 protected motor neurons at nM doses selective agonists of the DP1 and DP2 receptors BW245C and DK-PGD 2 respectively also significantly 4 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>583|APC|324|Complete__11751|TFDP2|7029|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 58852 17574754 74357 872 583 APC DP2 DP2 18 0.1 neurons at nM doses selective agonists of the DP1 and DP2 receptors BW245C and DK-PGD 2 respectively also significantly rescued motor 6 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>583|APC|324|Complete__11751|TFDP2|7029|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 58853 17574754 74358 8612 4458 GPI PGI PGI 18 0.6 agonist fluprostenol ( Fig 1 D and the prostacyclin (PGI PGI 2 IP receptor agonist carbaprostacyclin ( Fig 1 E significantly 1 JUMiner_v2.2 1 2 prostacyclin 0 2 4458 TotalCon:2<>1044|BGN|633|Complete__4458|GPI|2821|Complete__<>AvaiableGeneRif=2<>BEST:4458|GPI|0.000430668045800177<>ScoreDetail__1044|BGN|0.000352631672412787__4458|GPI|0.000430668045800177__ 0 0 0 0 0 58854 17574754 74358 16459 8893 PGF PGF PGF 5 0.0 In addition co-administration of the PGF 2_amp_#x3b1 FP receptor agonist fluprostenol ( Fig 1 D and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58855 17574754 74360 17594 9591 PTGDR DP1 DP1 5 1.1 Administration of PGD 2 DP1 DP2 FP IP and TP agonists alone had no effect 1 JUMiner_v2.2 1 0 0 2 9591 TotalCon:3<>30077|REEP5|7905|No_GeneRif__9591|PTGDR|5729|Complete__11749|TFDP1|7027|Complete__<>AvaiableGeneRif=2<>BEST:9591|PTGDR|0.00262777558796479<>ScoreDetail__11749|TFDP1|0.000292525961679099__9591|PTGDR|0.00262777558796479__ 0 0 0 0 0 58856 17574754 74360 16457 8891 PGD PGD PGD 2 0.0 Administration of PGD 2 DP1 DP2 FP IP and TP agonists alone had 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58857 17574754 74360 872 583 APC DP2 DP2 6 0.2 Administration of PGD 2 DP1 DP2 FP IP and TP agonists alone had no effect on 5 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>583|APC|324|Complete__11751|TFDP2|7029|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 58858 17574754 74361 17597 9594 PTGER2 EP2 EP2 10 0.3 We have previously determined that activation of the PGE 2 EP2 receptor and the PGD 2 DP1 receptor protect CA1 neurons 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58859 17574754 74361 17594 9591 PTGDR DP1 DP1 16 1.1 of the PGE 2 EP2 receptor and the PGD 2 DP1 receptor protect CA1 neurons in organotypic hippocampal slices treated with 1 JUMiner_v2.2 1 0 0 2 9591 TotalCon:3<>30077|REEP5|7905|No_GeneRif__9591|PTGDR|5729|Complete__11749|TFDP1|7027|Complete__<>AvaiableGeneRif=2<>BEST:9591|PTGDR|0.00262777558796479<>ScoreDetail__11749|TFDP1|0.000292525961679099__9591|PTGDR|0.00262777558796479__ 0 0 0 0 0 58860 17574754 74361 16457 8891 PGD PGD PGD 14 0.1 that activation of the PGE 2 EP2 receptor and the PGD 2 DP1 receptor protect CA1 neurons in organotypic hippocampal slices 6 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 58861 17574754 74361 3353 1368 CA1 CA1 CA1 19 0.0 2 EP2 receptor and the PGD 2 DP1 receptor protect CA1 neurons in organotypic hippocampal slices treated with NMDA 15 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58862 17574754 74362 3353 1368 CA1 CA1 CA1 9 0.0 Here we examined effects of additional prostaglandin receptors on CA1 neuronal survival in hippocampal slices treated acutely with NMDA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58863 17574754 74363 17598 9595 PTGER3 EP3 EP3 1 0.3 The EP3 agonist sulprostone exerted significant protection at pM_amp_#x2013 nM concentrations ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58864 17574754 74366 17598 9595 PTGER3 EP3 EP3 2 0.3 Administration of EP3 FP IP and TP agonists alone had no effect on 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58865 17574754 74366 3353 1368 CA1 CA1 CA1 13 0.0 FP IP and TP agonists alone had no effect on CA1 neuronal survival (data data not shown 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58866 17574754 74367 17597 9594 PTGER2 EP2 EP2 6 0.3 Recent studies have demonstrated that the EP2 receptor enhances inflammatory oxidative stress and synaptotoxicity in innate immunity 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58867 17574754 74368 17597 9594 PTGER2 EP2 EP2 10 0.3 These effects are distinct from the neuroprotective function of the EP2 receptor seen both in vitro in organotypic slices and in 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58868 17574754 74369 17597 9594 PTGER2 EP2 EP2 9 0.3 We investigated the effect of PGE 2 and the EP2 and EP3 receptors in vitro in a model of LPS 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58869 17574754 74369 17598 9595 PTGER3 EP3 EP3 9 0.3 We investigated the effect of PGE 2 and the EP2 and EP3 receptors in vitro in a model of LPS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58870 17574754 74369 17598 9595 PTGER3 EP3 EP3 11 0.3 investigated the effect of PGE 2 and the EP2 and EP3 receptors in vitro in a model of LPS mediated inflammation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58871 17574754 74369 24053 12728 VWS LPS LPS 19 0.0 EP2 and EP3 receptors in vitro in a model of LPS mediated inflammation 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58872 17574754 74370 24053 12728 VWS LPS LPS 8 0.0 In this model stimulation of hippocampal slices with LPS (0.1_amp_#x2013;5 0.1_amp_#x2013 5 _amp_#x3bc;g/ml) _amp_#x3bc g ml leads to CA1 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58873 17574754 74370 3353 1368 CA1 CA1 CA1 13 0.0 LPS (0.1_amp_#x2013;5 0.1_amp_#x2013 5 _amp_#x3bc;g/ml) _amp_#x3bc g ml leads to CA1 pyramidal death as measured by PI fluorescence 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58874 17574754 74371 24053 12728 VWS LPS LPS 12 0.0 PGE 2 at nM concentrations significantly enhanced the neurotoxicity of LPS ( Fig 3 A 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58875 17574754 74372 17597 9594 PTGER2 EP2 EP2 4 0.3 Selective activation of the EP2 and EP3 receptors also increased LPS-mediated CA1 neurotoxicity ( Fig 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58876 17574754 74372 17598 9595 PTGER3 EP3 EP3 4 0.3 Selective activation of the EP2 and EP3 receptors also increased LPS-mediated CA1 neurotoxicity ( Fig 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58877 17574754 74372 17598 9595 PTGER3 EP3 EP3 6 0.3 Selective activation of the EP2 and EP3 receptors also increased LPS-mediated CA1 neurotoxicity ( Fig 3 B 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58878 17574754 74372 24053 12728 VWS LPS LPS-mediated 10 0.0 Selective activation of the EP2 and EP3 receptors also increased LPS-mediated CA1 neurotoxicity ( Fig 3 B and C 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58879 17574754 74372 3353 1368 CA1 CA1 CA1 11 0.0 activation of the EP2 and EP3 receptors also increased LPS-mediated CA1 neurotoxicity ( Fig 3 B and C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58880 17574754 74374 17610 9605 PTGS2 COX-2 COX-2 2 1.0 Induction of COX-2 activity and production of downstream prostaglandins is associated in a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58881 17574754 74375 16457 8891 PGD PGD PGD 15 0.0 models have identified paradoxical neuroprotective effects of PGE 2 and PGD 2 receptors that have been confirmed in vivo in models 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58882 17574754 74377 16457 8891 PGD PGD PGD 13 0.0 slices that are chronically exposed to glutamate reuptake inhibitors both PGD 2 DP receptors as well as the PGF 2_amp_#x3b1 FP 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>8891|PGD|5226|No_GeneRif__8923|PHGDH|26227|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58883 17574754 74377 16459 8893 PGF PGF PGF 21 0.0 inhibitors both PGD 2 DP receptors as well as the PGF 2_amp_#x3b1 FP and prostacyclin IP receptors rescued motor neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58884 17574754 74378 17610 9605 PTGS2 COX-2 COX-2 0 1.0 COX-2 inhibition has been shown to be protective in this in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58885 17574754 74378 20996 11179 SOD1 ALS ALS 22 0.0 model as well as in the transgenic model of Familial ALS 3 7 and 8 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00135542706503777<>ScoreDetail__5468|IGFALS|0.000184791647417537__11179|SOD1|0.00135542706503777__ 0 0 0 0 0 58886 17574754 74379 17610 9605 PTGS2 COX-2 COX-2 13 1.0 that the DP FP and IP receptors do not mediate COX-2 toxicity in this in vitro model and from our previous 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58887 17574754 74379 17597 9594 PTGER2 EP2 EP2 28 0.3 in vitro model and from our previous studies 3 the EP2 and EP3 receptors can also be excluded since they too 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58888 17574754 74379 17598 9595 PTGER3 EP3 EP3 28 0.3 in vitro model and from our previous studies 3 the EP2 and EP3 receptors can also be excluded since they too 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58889 17574754 74379 17598 9595 PTGER3 EP3 EP3 30 0.3 model and from our previous studies 3 the EP2 and EP3 receptors can also be excluded since they too rescue motor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58890 17574754 74381 17598 9595 PTGER3 EP3 EP3 5 0.3 Stimulation of the PGE 2 EP3 receptor with picomolar concentrations of agonist resulted in significant rescue 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58891 17574754 74381 3353 1368 CA1 CA1 CA1 17 0.0 with picomolar concentrations of agonist resulted in significant rescue of CA1 pyramidal neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58892 17574754 74382 17598 9595 PTGER3 EP3 EP3 13 0.3 consistent with previous data obtained in spinal cord slices where EP3 activation rescued motor neurons subjected to chronic glutamate toxicity 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58893 17574754 74382 17598 9595 PTGER3 EP3 EP3 26 0.3 rescued motor neurons subjected to chronic glutamate toxicity 3 here EP3 activation was associated with increased levels of the pro-survival phosphorylated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58894 17574754 74382 543 391 AKT1 AKT AKT 39 0.3 associated with increased levels of the pro-survival phosphorylated form of AKT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58895 17574754 74384 17597 9594 PTGER2 EP2 EP2 19 0.3 dependent on cAMP signaling as is the case for the EP2 and DP1 receptors we hypothesize that this is the case 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58896 17574754 74384 17594 9591 PTGDR DP1 DP1 21 1.1 cAMP signaling as is the case for the EP2 and DP1 receptors we hypothesize that this is the case and may 1 JUMiner_v2.2 1 0 0 2 9591 TotalCon:3<>30077|REEP5|7905|No_GeneRif__9591|PTGDR|5729|Complete__11749|TFDP1|7027|Complete__<>AvaiableGeneRif=2<>BEST:9591|PTGDR|0.00262777558796479<>ScoreDetail__11749|TFDP1|0.000292525961679099__9591|PTGDR|0.00262777558796479__ 0 0 0 0 0 58897 17574754 74386 16459 8893 PGF PGF PGF 9 0.0 A similar divergence of effect was found for the PGF 2_amp_#x3b1 FP receptor which had no effect on CA1 neuronal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58898 17574754 74386 3353 1368 CA1 CA1 CA1 18 0.0 the PGF 2_amp_#x3b1 FP receptor which had no effect on CA1 neuronal survival unlike its significant protective effect in the spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58899 17574754 74389 17597 9594 PTGER2 EP2 EP2 6 0.3 In hippocampal slices activation of the EP2 15 and 16 and EP3 ( Fig 2 receptor rescues 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58900 17574754 74389 17598 9595 PTGER3 EP3 EP3 11 0.3 hippocampal slices activation of the EP2 15 and 16 and EP3 ( Fig 2 receptor rescues CA1 neurons stimulated with NMDA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58901 17574754 74389 3353 1368 CA1 CA1 CA1 18 0.0 15 and 16 and EP3 ( Fig 2 receptor rescues CA1 neurons stimulated with NMDA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58902 17574754 74390 17597 9594 PTGER2 EP2 EP2 23 0.3 of neurotoxic cytokines and reactive oxygen species stimulation of the EP2 or EP3 receptor now increases LPS-mediated CA1 toxicity 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58903 17574754 74390 17598 9595 PTGER3 EP3 EP3 25 0.3 cytokines and reactive oxygen species stimulation of the EP2 or EP3 receptor now increases LPS-mediated CA1 toxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58904 17574754 74390 24053 12728 VWS LPS LPS 5 0.0 However in slices stimulated with LPS which injures neurons secondarily via microglial production of neurotoxic cytokines 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58905 17574754 74390 24053 12728 VWS LPS LPS-mediated 29 0.0 species stimulation of the EP2 or EP3 receptor now increases LPS-mediated CA1 toxicity 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58906 17574754 74390 3353 1368 CA1 CA1 CA1 30 0.0 stimulation of the EP2 or EP3 receptor now increases LPS-mediated CA1 toxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58907 17574754 74391 17597 9594 PTGER2 EP2 EP2 27 0.3 addition of either PGE 2 (10_amp_#x2013;100 10_amp_#x2013 100 nM the EP2 agonist butaprost (200 200 nM or the EP3 agonist sulprostone 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58908 17574754 74391 17598 9595 PTGER3 EP3 EP3 34 0.3 nM the EP2 agonist butaprost (200 200 nM or the EP3 agonist sulprostone (10 10 nM consistently enhanced LPS-induced CA1 PI 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58909 17574754 74391 24053 12728 VWS LPS LPS 10 0.0 While we did not find a consistent dose response of LPS and increasing CA1 toxicity in this paradigm the addition of 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58910 17574754 74391 3353 1368 CA1 CA1 CA1 13 0.0 not find a consistent dose response of LPS and increasing CA1 toxicity in this paradigm the addition of either PGE 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58911 17574754 74391 24053 12728 VWS LPS LPS-induced 41 0.0 or the EP3 agonist sulprostone (10 10 nM consistently enhanced LPS-induced CA1 PI fluorescence 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58912 17574754 74391 3353 1368 CA1 CA1 CA1 42 0.0 the EP3 agonist sulprostone (10 10 nM consistently enhanced LPS-induced CA1 PI fluorescence 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58913 17574754 74392 17597 9594 PTGER2 EP2 EP2 8 0.3 The increased toxicity of LPS with addition of EP2/EP3 EP2 EP3 receptor agonists is relevant to recent in vivo studies 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58914 17574754 74392 17598 9595 PTGER3 EP3 EP3 8 0.3 The increased toxicity of LPS with addition of EP2/EP3 EP2 EP3 receptor agonists is relevant to recent in vivo studies demonstrating 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58915 17574754 74392 24053 12728 VWS LPS LPS 4 0.0 The increased toxicity of LPS with addition of EP2/EP3 EP2 EP3 receptor agonists is relevant 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58916 17574754 74393 17597 9594 PTGER2 EP2 EP2 10 0.3 For example in the LPS model of innate immunity the EP2 receptor mediates a major component of inflammatory oxidative stress and 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58917 17574754 74393 24053 12728 VWS LPS LPS 4 0.0 For example in the LPS model of innate immunity the EP2 receptor mediates a major 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58918 17574754 74394 14535 7873 NOS2A iNOS iNOS 7 1.0 One potential mechanism is via induction of iNOS production of NO and production of reactive oxygen species alternatively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 58919 17574754 74395 926 620 APP amyloid amyloid 6 1.0 In addition in a model of amyloid deposition the EP2 receptor similarly promotes an increase in neuronal 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 58920 17574754 74395 17597 9594 PTGER2 EP2 EP2 9 0.3 In addition in a model of amyloid deposition the EP2 receptor similarly promotes an increase in neuronal lipid peroxidation 13 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58921 17574754 74396 17597 9594 PTGER2 EP2 EP2 11 0.3 together these data suggest a dichotomy of function of the EP2 receptor in which the EP2 receptor promotes primary neuroprotection in 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58922 17574754 74396 17597 9594 PTGER2 EP2 EP2 16 0.3 dichotomy of function of the EP2 receptor in which the EP2 receptor promotes primary neuroprotection in models of glutamate toxicity and 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58923 17574754 74398 17597 9594 PTGER2 EP2 EP2 16 0.3 dispersed hippocampal neurons are protected from toxicity with application of EP2 receptor agonist suggesting that activation of the neuronal EP2 receptor 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58924 17574754 74398 17597 9594 PTGER2 EP2 EP2 25 0.3 of EP2 receptor agonist suggesting that activation of the neuronal EP2 receptor promotes a neuroprotective response supporting this is the dependence 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58925 17574754 74399 17597 9594 PTGER2 EP2 EP2 25 0.3 paracrine synaptic and neuronal injury and genetic ablation of the EP2 receptor in this paradigm is protective 20 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58926 17574754 74399 24053 12728 VWS LPS LPS 6 0.0 Conversely stimulation of primary microglia with LPS results in production of soluble factors that induce paracrine synaptic 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58927 17574754 74401 17597 9594 PTGER2 EP2 EP2 4 0.3 The protective function of EP2 signaling in vivo in models of excitotoxicity and cerebral ischemia 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58928 17574754 74401 17597 9594 PTGER2 EP2 EP2 23 0.3 cerebral ischemia 15 and 16 and the neurotoxic effect of EP2 receptor signaling in the LPS 17 19 and 20 and 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58929 17574754 74401 926 620 APP amyloid amyloid 35 1.0 receptor signaling in the LPS 17 19 and 20 and amyloid models 13 lends support to this hypothesis 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 58930 17574754 74401 24053 12728 VWS LPS LPS 28 0.0 and the neurotoxic effect of EP2 receptor signaling in the LPS 17 19 and 20 and amyloid models 13 lends support 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 58931 17574754 74402 17597 9594 PTGER2 EP2 EP2 18 0.3 anti-inflammatory drugs (NSAIDs), NSAIDs which should reduce signaling through the EP2 receptor by decreasing levels of PGE 2 would have similar 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58932 17574754 74402 17597 9594 PTGER2 EP2 EP2 35 0.3 PGE 2 would have similar effects on neuronal viability as EP2 inhibition alone 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00213752998609205<>ScoreDetail__9594|PTGER2|0.00213752998609205__14534|SPAG11B|0.000145548851487245__ 0 0 0 0 0 58933 17574754 74402 17610 9605 PTGS2 COX COX 5 0.0 A larger question is whether COX inhibition by non-steroidal anti-inflammatory drugs (NSAIDs), NSAIDs which should reduce 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 58934 17574754 74403 17610 9605 PTGS2 COX-2 COX-2 9 1.0 In models of in vitro and in vivo excitotoxicity COX-2 inhibition is clearly neuroprotective 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59185 17582695 74871 23936 12693 VIP VIP VIP 12 2.2 vasoactive neuropeptides (VNs) VNs such as vasoactive intestinal peptide (VIP) VIP and pituitary adenylate cyclase activating polypeptide (PACAP) PACAP has been 1 JUMiner_v2.2 1 0 0 2 12693 TotalCon:2<>12693|VIP|7432|Complete__23228|CPAMD8|27151|Complete__<>AvaiableGeneRif=2<>BEST:12693|VIP|0.00122160148975791<>ScoreDetail__23228|CPAMD8|0__12693|VIP|0.00122160148975791__ 0 0 0 0 0 59186 17582695 74871 349 241 ADCYAP1 PACAP PACAP 19 3.3 peptide (VIP) VIP and pituitary adenylate cyclase activating polypeptide (PACAP) PACAP has been postulated as a cause for some fatigue-related conditions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59187 17582695 74872 8595 19680 GPBAR1 GPCR GPCRs 8 0.6 VN receptors are class II G protein-coupled receptors (GPCRs) GPCRs which couple primarily to the adenylate cyclase (AC)-cyclic AC -cyclic 13 JUMiner_v2.2 1 2 g protein-coupled receptor 0 2 14298 TotalCon:15<>19680|GPBAR1|151306|Complete__24884|OXER1|165140|Complete__18274|CYSLTR2|57105|Complete__4042|FZD4|8322|Complete__23624|GPR151|134391|Complete__23626|GPR166P|442206|No_GeneRif__30224|GPR172A|79581|No_GeneRif__30225|GPR172B|55065|No_GeneRif__18510|GPRC6A|222545|Complete__19719|LGR6|59352|No_GeneRif__14298|LPAR3|23566|Complete__17962|MRGPRX1|259249|No_GeneRif__17980|MRGPRX3|117195|Complete__17617|MRGPRX4|117196|No_GeneRif__13300|GPR61|83873|Complete__<>AvaiableGeneRif=9<>BEST:14298|LPAR3|0.00104185486299307<>ScoreDetail__23624|GPR151|0.000317073170731707__17980|MRGPRX3|0.00021680216802168__19680|GPBAR1|0.000982292014700969__18510|GPRC6A|0.0004516711833785__13300|GPR61|0.000670731707317073__18274|CYSLTR2|0.000692855601122383__14298|LPAR3|0.00104185486299307__4042|FZD4|0.000587427001030574__24884|OXER1|0.00061617458279846__ 0 0 0 0 0 59188 17582695 74873 20996 11179 SOD1 ALS ALS 12 0.5 in multiple sclerosis (MS) MS and amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59189 17582695 74876 20996 11179 SOD1 ALS ALS 15 0.5 that autoimmune dysfunction of VNs may contribute to MS and ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59190 17582695 74877 20996 11179 SOD1 ALS ALS 3 0.5 While MS and ALS differ in important respects they have common pathogenic features including 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59191 17582695 74879 20996 11179 SOD1 ALS ALS 5 0.5 Diseases such as MS and ALS may represent related conditions resulting from variation in expression of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59192 17582695 74884 23936 12693 VIP VIP VIP 12 2.2 vasoactive neuropeptides (VNs) VNs such as vasoactive intestinal peptide (VIP) VIP and pituitary adenylate cyclase activating polypeptide (PACAP) PACAP has been 1 JUMiner_v2.2 1 0 0 2 12693 TotalCon:2<>12693|VIP|7432|Complete__23228|CPAMD8|27151|Complete__<>AvaiableGeneRif=2<>BEST:12693|VIP|0.00122160148975791<>ScoreDetail__23228|CPAMD8|0__12693|VIP|0.00122160148975791__ 0 0 0 0 0 59193 17582695 74884 349 241 ADCYAP1 PACAP PACAP 19 3.3 peptide (VIP) VIP and pituitary adenylate cyclase activating polypeptide (PACAP) PACAP has been postulated as a cause for some fatigue-related conditions 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59194 17582695 74887 8595 19680 GPBAR1 GPCR GPCRs 8 0.6 VN receptors are class II G protein-coupled receptors (GPCRs) GPCRs which couple primarily to the adenylate cyclase (AC)-cyclic AC -cyclic 13 JUMiner_v2.2 1 2 g protein-coupled receptor 0 2 14298 TotalCon:15<>19680|GPBAR1|151306|Complete__24884|OXER1|165140|Complete__18274|CYSLTR2|57105|Complete__4042|FZD4|8322|Complete__23624|GPR151|134391|Complete__23626|GPR166P|442206|No_GeneRif__30224|GPR172A|79581|No_GeneRif__30225|GPR172B|55065|No_GeneRif__18510|GPRC6A|222545|Complete__19719|LGR6|59352|No_GeneRif__14298|LPAR3|23566|Complete__17962|MRGPRX1|259249|No_GeneRif__17980|MRGPRX3|117195|Complete__17617|MRGPRX4|117196|No_GeneRif__13300|GPR61|83873|Complete__<>AvaiableGeneRif=9<>BEST:14298|LPAR3|0.00104185486299307<>ScoreDetail__23624|GPR151|0.000317073170731707__17980|MRGPRX3|0.00021680216802168__19680|GPBAR1|0.000982292014700969__18510|GPRC6A|0.0004516711833785__13300|GPR61|0.000670731707317073__18274|CYSLTR2|0.000692855601122383__14298|LPAR3|0.00104185486299307__4042|FZD4|0.000587427001030574__24884|OXER1|0.00061617458279846__ 0 0 0 0 0 59195 17582695 74890 567 877 ALDH7A1 PDE PDE 7 0.0 Importantly cAMP effects are maintained by phosphodiesterase (PDE) PDE inhibitors which may have implications for treatment of postulated cAMP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59196 17582695 74892 20996 11179 SOD1 ALS ALS 12 0.5 in multiple sclerosis (MS) MS and amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59197 17582695 74896 20996 11179 SOD1 ALS ALS 15 0.5 that autoimmune dysfunction of VNs may contribute to MS and ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59198 17582695 74897 20996 11179 SOD1 ALS ALS 4 0.5 Aetiology of MS and ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59199 17582695 74898 20996 11179 SOD1 ALS ALS 5 0.5 The causes of MS and ALS are unknown 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59200 17582695 74899 20996 11179 SOD1 ALS ALS 7 0.5 While complex diseases such as MS and ALS are thought likely to demonstrate multiple genetic and environmental factors 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59201 17582695 74900 20996 11179 SOD1 ALS ALS 8 0.5 Exposure to environmental chemicals increases risk of sporadic ALS particularly industrial herbicide/pesticide herbicide pesticide exposure 4 and military service 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59202 17582695 74900 20996 11179 SOD1 ALS ALS 29 0.5 possibly Gulf War service may also hold an association for ALS 5 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59203 17582695 74901 20996 11179 SOD1 ALS ALS 16 0.5 s disease (PD) PD dementia complex (PDC) PDC and atypical ALS which may have been attributed to Rotenone a natural toxin 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59204 17582695 74901 16271 8759 PDC PDC PDC 13 0.0 have experienced Parkinson_amp_#x2019 s disease (PD) PD dementia complex (PDC) PDC and atypical ALS which may have been attributed to Rotenone 1 JUMiner_v2.2 1 0 0 2 9153 TotalCon:2<>8759|PDC|5132|Complete__9153|PNKD|25953|Complete__<>AvaiableGeneRif=2<>BEST:9153|PNKD|0.00048780487804878<>ScoreDetail__8759|PDC|0.000154043645699615__9153|PNKD|0.00048780487804878__ 0 0 0 0 0 59205 17582695 74902 349 241 ADCYAP1 PACAP PACAP 1 3.3 Interestingly PACAP protects against Rotenone neuronal injury 8 and 9 hence autoimmune 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59206 17582695 74902 349 241 ADCYAP1 PACAP PACAP 14 3.3 Rotenone neuronal injury 8 and 9 hence autoimmune compromise of PACAP may have predisposed to neuronal pathology of Parkinson_amp_#x2019 s or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59207 17582695 74902 20996 11179 SOD1 ALS ALS 24 0.5 may have predisposed to neuronal pathology of Parkinson_amp_#x2019 s or ALS type because of its specific anatomical distribution 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59208 17582695 74904 10480 5962 IL10 IL-10 IL-10 11 1.0 1 25-dihydroxyvitamin D(3) D 3 may protect against MS via IL-10 11 a cytokine associated with VN activity in inflammatory contexts 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59209 17582695 74905 20996 11179 SOD1 ALS ALS 6 0.5 As noted above clinical presentation of ALS is not confined to motor neuron abnormality 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59210 17582695 74907 20996 11179 SOD1 ALS ALS 9 0.5 Behavioural changes such as apathy occur at onset of ALS suggesting this link with fronto-temporal dementia 15 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59211 17582695 74908 20996 11179 SOD1 ALS ALS 17 0.5 volume and correlates with psychopathological findings in later stages of ALS 16 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59212 17582695 74909 20996 11179 SOD1 ALS ALS 5 0.5 Alterations in cortical functions in ALS suggest upper motor neuron pathology 17 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59213 17582695 74910 20996 11179 SOD1 ALS ALS 9 0.5 Moreover cerebral degeneration is predictive of reduced survival in ALS 18 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59214 17582695 74914 20996 11179 SOD1 ALS ALS 19 0.5 may be early and significant events in both MS and ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59215 17582695 74916 9230 4910 HIF1A HIF-1 HIF-1 5 0.6 IL-1beta and hypoxia inducible factor-1 (HIF-1) HIF-1 play important roles in influencing vessel plasticity along with vascular 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59216 17582695 74916 23910 12680 VEGFA VEGF VEGF 19 2.8 influencing vessel plasticity along with vascular endothelial growth factor (VEGF) VEGF 22 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59217 17582695 74916 10437 5992 IL1B IL1BETA IL-1beta 0 0.0 IL-1beta and hypoxia inducible factor-1 (HIF-1) HIF-1 play important roles in 11 JUMiner_v2.2 1 1 LongSymbol 0 0 0 0 0 0 0 0 59218 17582695 74917 23910 12680 VEGFA VEGF VEGF 1 2.8 Serum VEGF is higher in ALS in human samples than controls 23 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59219 17582695 74917 20996 11179 SOD1 ALS ALS 5 0.5 Serum VEGF is higher in ALS in human samples than controls 23 as it is in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59220 17582695 74917 23910 12680 VEGFA VEGF VEGF 18 2.8 samples than controls 23 as it is in MS where VEGF shows a correlation with length of spinal cord lesions 24 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59221 17582695 74918 20996 11179 SOD1 SOD1 SOD1 16 0.5 cortex and brainstem although not in spinal cord of transgenic SOD1 (G93A) G93A mice models of ALS 25 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59222 17582695 74918 20996 11179 SOD1 ALS ALS 21 0.5 spinal cord of transgenic SOD1 (G93A) G93A mice models of ALS 25 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59223 17582695 74919 23910 12680 VEGFA VEGF VEGF 4 2.8 High erythropoietin and low VEGF in CSF from hypoxemic ALS patients suggest an abnormal response 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59224 17582695 74919 11629 6493 LAMC2 CSF CSF 6 0.3 High erythropoietin and low VEGF in CSF from hypoxemic ALS patients suggest an abnormal response to hypoxia 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 59225 17582695 74919 20996 11179 SOD1 ALS ALS 9 0.5 High erythropoietin and low VEGF in CSF from hypoxemic ALS patients suggest an abnormal response to hypoxia compared with hypoxic 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59226 17582695 74920 6708 3415 EPO EPO EPO 4 1.0 Moreover low concentrations of EPO in CSF point to a rapid progression of disease that 1 JUMiner_v2.2 1 0 0 2 3415 TotalCon:3<>3415|EPO|2056|Complete__3423|EPX|8288|Complete__11820|TIMP1|7076|Complete__<>AvaiableGeneRif=3<>BEST:3415|EPO|0.000724225647164447<>ScoreDetail__3423|EPX|0.000685002594706798__3415|EPO|0.000724225647164447__11820|TIMP1|0.000670100925147182__ 0 0 0 0 0 59227 17582695 74920 11629 6493 LAMC2 CSF CSF 6 0.3 Moreover low concentrations of EPO in CSF point to a rapid progression of disease that may be 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 59228 17582695 74923 20996 11179 SOD1 ALS ALS 3 0.5 While MS and ALS differ in important respects they have common pathogenic features including 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59229 17582695 74924 20996 11179 SOD1 ALS ALS 15 0.5 are modulated by certain cytokines in neurodegenerative disorders such as ALS and PD e.g. IL-1beta and IL-6 32 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59230 17582695 74924 10463 6018 IL6 IL-6 IL-6 21 1.3 neurodegenerative disorders such as ALS and PD e.g. IL-1beta and IL-6 32 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59231 17582695 74924 10437 5992 IL1B IL1BETA IL-1beta 19 0.1 cytokines in neurodegenerative disorders such as ALS and PD e.g. IL-1beta and IL-6 32 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59232 17582695 74925 20996 11179 SOD1 ALS ALS 30 0.5 is suggested associated with oxidative stress and glial activation in ALS 33 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59233 17582695 74927 20996 11179 SOD1 ALS ALS 15 0.5 stages of disease play causative roles in the pathogenesis of ALS in rodent models 35 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59234 17582695 74928 12337 6871 MAPK1 p38 p38 1 1.7 The p38 mitogen-activated protein kinase (p38MAPK) p38MAPK is activated by a variety 1 JUMiner_v2.2 1 0 0 2 6876 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6876|MAPK14|0.000684092432322173<>ScoreDetail__1189|AHSA1|0.00016260162601626__6878|MAPK4|0.000529616724738676__6871|MAPK1|0.000670699643017464__6876|MAPK14|0.000684092432322173__ 0 0 0 0 0 59235 17582695 74930 20996 11179 SOD1 ALS ALS 16 0.5 to the development and progression of motor neuron pathology in ALS 36 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59236 17582695 74931 12337 6871 MAPK1 p38 p38 2 1.7 Inhibition of p38 signalling activated by NO exposure in rat models of MS 1 JUMiner_v2.2 1 0 0 2 6876 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6876|MAPK14|0.000684092432322173<>ScoreDetail__1189|AHSA1|0.00016260162601626__6878|MAPK4|0.000529616724738676__6871|MAPK1|0.000670699643017464__6876|MAPK14|0.000684092432322173__ 0 0 0 0 0 59237 17582695 74932 12337 6871 MAPK1 p38 p38 2 1.7 Activation of p38 MAPK is associated with upregulation of TNF alpha receptors in 1 JUMiner_v2.2 1 0 0 2 6876 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6876|MAPK14|0.000684092432322173<>ScoreDetail__1189|AHSA1|0.00016260162601626__6878|MAPK4|0.000529616724738676__6871|MAPK1|0.000670699643017464__6876|MAPK14|0.000684092432322173__ 0 0 0 0 0 59238 17582695 74932 12337 6871 MAPK1 MAPK MAPK 3 1.7 Activation of p38 MAPK is associated with upregulation of TNF alpha receptors in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59239 17582695 74932 22551 11892 TNF TNF TNF 9 1.0 Activation of p38 MAPK is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59240 17582695 74932 20996 11179 SOD1 ALS ALS 22 0.5 in the spinal motor neurons of mouse models of familial ALS 38 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59241 17582695 74933 22551 11892 TNF TNF TNF 1 1.0 Thus TNF alpha signalling is postulated to have a key role in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59242 17582695 74933 20996 11179 SOD1 ALS ALS 12 0.5 alpha signalling is postulated to have a key role in ALS 39 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59243 17582695 74934 12337 6871 MAPK1 p38 p38 1 1.7 Importantly p38 MAPK pathway is selectively inhibited by PACAP in hypoxic activation 1 JUMiner_v2.2 1 0 0 2 6876 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6876|MAPK14|0.000684092432322173<>ScoreDetail__1189|AHSA1|0.00016260162601626__6878|MAPK4|0.000529616724738676__6871|MAPK1|0.000670699643017464__6876|MAPK14|0.000684092432322173__ 0 0 0 0 0 59244 17582695 74934 12337 6871 MAPK1 MAPK MAPK 2 1.7 Importantly p38 MAPK pathway is selectively inhibited by PACAP in hypoxic activation of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59245 17582695 74934 349 241 ADCYAP1 PACAP PACAP 8 3.3 Importantly p38 MAPK pathway is selectively inhibited by PACAP in hypoxic activation of microglial cells 40 suggesting neuroprotection in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59246 17582695 74935 349 241 ADCYAP1 PACAP PACAP 1 3.3 Moreover PACAP exerts this protective effect in endothelial cells protecting them against 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59247 17582695 74936 20996 11179 SOD1 ALS ALS 16 0.5 and proinflammatory cytokines are implicated in a lipopolysaccharide model of ALS suggesting that environmental factors and innate immunity are linked 42 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59248 17582695 74937 20996 11179 SOD1 ALS ALS 11 0.5 and inflammatory responses appear to magnify motor neuron degeneration in ALS 43 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59249 17582695 74938 22551 11892 TNF TNFalpha TNFalpha 7 1.0 Modest increases in multiple synergistic cytokines including TNFalpha TGFbeta1 and TGFbeta2 may produce a disproportionately severe activation of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59250 17582695 74939 20996 11179 SOD1 ALS ALS 8 0.5 Moreover TGFbeta1 is significantly higher in long duration ALS than short duration ALS possibly indicating severity and duration of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59251 17582695 74939 20996 11179 SOD1 ALS ALS 12 0.5 is significantly higher in long duration ALS than short duration ALS possibly indicating severity and duration of the disease 45 and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59252 17582695 74944 20996 11179 SOD1 ALS ALS 7 0.5 Also neurodegenerative disorders such as PD and ALS have been termed protein misfolding disorders because of their association 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59253 17582695 74944 9691 5232 HSPA1A HSP HSPs 25 0.9 their association with variable levels of heat shock proteins (HSPs) HSPs 50 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59254 17582695 74945 9691 5232 HSPA1A HSP HSPs 0 0.9 HSPs may have a role in postulated VN autoimmune disorders 51 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59255 17582695 74946 20996 11179 SOD1 ALS ALS 6 0.5 Vasoactive neuropeptide dysfunction in MS and ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59256 17582695 74947 20996 11179 SOD1 ALS ALS 13 0.5 critical role in neuronal survival however in a series of ALS patients CSF levels of VIP were found to be significantly 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59257 17582695 74947 11629 6493 LAMC2 CSF CSF 15 0.3 in neuronal survival however in a series of ALS patients CSF levels of VIP were found to be significantly lower compared 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 59258 17582695 74947 23936 12693 VIP VIP VIP 18 2.2 however in a series of ALS patients CSF levels of VIP were found to be significantly lower compared with controls 52 1 JUMiner_v2.2 1 0 0 2 12693 TotalCon:2<>12693|VIP|7432|Complete__23228|CPAMD8|27151|Complete__<>AvaiableGeneRif=2<>BEST:12693|VIP|0.00122160148975791<>ScoreDetail__23228|CPAMD8|0__12693|VIP|0.00122160148975791__ 0 0 0 0 0 59259 17582695 74948 23936 12693 VIP VIP VIP 0 2.2 VIP has demonstrated potent effects on neurite outgrowth in spinal cord 1 JUMiner_v2.2 1 0 0 2 12693 TotalCon:2<>12693|VIP|7432|Complete__23228|CPAMD8|27151|Complete__<>AvaiableGeneRif=2<>BEST:12693|VIP|0.00122160148975791<>ScoreDetail__23228|CPAMD8|0__12693|VIP|0.00122160148975791__ 0 0 0 0 0 59260 17582695 74948 20996 11179 SOD1 ALS ALS 18 0.5 in spinal cord cultures suggesting its use in treatment of ALS 53 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59261 17582695 74949 23936 12693 VIP VIP VIP 7 2.2 Interestingly Sun et al 54 noted impaired VIP receptor (VPAC2) VPAC2 production in activated T cells in MS 1 JUMiner_v2.2 1 0 0 2 12693 TotalCon:2<>12693|VIP|7432|Complete__23228|CPAMD8|27151|Complete__<>AvaiableGeneRif=2<>BEST:12693|VIP|0.00122160148975791<>ScoreDetail__23228|CPAMD8|0__12693|VIP|0.00122160148975791__ 0 0 0 0 0 59262 17582695 74949 23938 12695 VIPR2 VPAC2 VPAC2 9 3.0 Interestingly Sun et al 54 noted impaired VIP receptor (VPAC2) VPAC2 production in activated T cells in MS patients suggesting transcription 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59263 17582695 74949 23938 12695 VIPR2 VPAC2 VPAC2 26 3.0 MS patients suggesting transcription irregularity at promoter regions of the VPAC2 gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59264 17582695 74950 23936 12693 VIP VIP VIP 11 2.2 finding may be extremely important as more widespread impairment of VIP if proven in patients with MS may explain the complete 1 JUMiner_v2.2 1 0 0 2 12693 TotalCon:2<>12693|VIP|7432|Complete__23228|CPAMD8|27151|Complete__<>AvaiableGeneRif=2<>BEST:12693|VIP|0.00122160148975791<>ScoreDetail__23228|CPAMD8|0__12693|VIP|0.00122160148975791__ 0 0 0 0 0 59265 17582695 74954 8595 19680 GPBAR1 GPCR GPCRs 3 0.6 As noted above GPCRs transduce signals promoting cellular survival and neurotrophic activity 13 JUMiner_v2.2 1 2 g protein-coupled receptor 0 2 14298 TotalCon:15<>19680|GPBAR1|151306|Complete__24884|OXER1|165140|Complete__18274|CYSLTR2|57105|Complete__4042|FZD4|8322|Complete__23624|GPR151|134391|Complete__23626|GPR166P|442206|No_GeneRif__30224|GPR172A|79581|No_GeneRif__30225|GPR172B|55065|No_GeneRif__18510|GPRC6A|222545|Complete__19719|LGR6|59352|No_GeneRif__14298|LPAR3|23566|Complete__17962|MRGPRX1|259249|No_GeneRif__17980|MRGPRX3|117195|Complete__17617|MRGPRX4|117196|No_GeneRif__13300|GPR61|83873|Complete__<>AvaiableGeneRif=9<>BEST:14298|LPAR3|0.00104185486299307<>ScoreDetail__23624|GPR151|0.000317073170731707__17980|MRGPRX3|0.00021680216802168__19680|GPBAR1|0.000982292014700969__18510|GPRC6A|0.0004516711833785__13300|GPR61|0.000670731707317073__18274|CYSLTR2|0.000692855601122383__14298|LPAR3|0.00104185486299307__4042|FZD4|0.000587427001030574__24884|OXER1|0.00061617458279846__ 0 0 0 0 0 59266 17582695 74956 349 241 ADCYAP1 PACAP PACAP 1 3.3 Moreover PACAP expression in the ventral horn of the spinal cord is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59267 17582695 74956 349 241 ADCYAP1 PACAP PACAP 23 3.3 in response to sciatic nerve transection suggesting a role for PACAP in repair or regeneration of motor neurons 57 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59268 17582695 74957 23936 12693 VIP VIP VIP 1 2.2 Similarly VIP may have a role in MS treatment 58 1 JUMiner_v2.2 1 0 0 2 12693 TotalCon:2<>12693|VIP|7432|Complete__23228|CPAMD8|27151|Complete__<>AvaiableGeneRif=2<>BEST:12693|VIP|0.00122160148975791<>ScoreDetail__23228|CPAMD8|0__12693|VIP|0.00122160148975791__ 0 0 0 0 0 59269 17582695 74958 20996 11179 SOD1 ALS ALS 18 0.5 in cultured spinal motor neurons indicating a possible role in ALS treatment 59 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 59270 17582695 74958 567 877 ALDH7A1 PDE PDE 0 0.0 PDE inhibitors have been found to be neuroprotective in cultured spinal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59271 17582695 74959 567 877 ALDH7A1 PDE PDE 0 0.0 PDE inhibitors are also being considered as novel therapies for MS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59272 17582695 74963 8240 4232 GDNF GDNF GDNF 14 1.2 cells may involve glial cell line derived neurotrophic factor (GDNF) GDNF around host motor neurons produced by grafted cells 68 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 59273 17582695 74966 20996 11179 SOD1 ALS ALS 5 0.5 Diseases such as MS and ALS may represent related conditions resulting from variation in expression of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000778010267622989<>ScoreDetail__5468|IGFALS|0.000516679348796137__11179|SOD1|0.000778010267622989__ 0 0 0 0 0 46957 17597167 59384 10437 5992 IL1B IL-1 IL-1 6 1.3 The proinflammatory cytokines of which interleukin-1 (IL-1), IL-1 IL-6 and tumour necrosis factor-_amp_#x3b1 (TNF-_amp_#x3b1;) TNF-_amp_#x3b1 are involved in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46958 17597167 59384 10463 6018 IL6 IL-6 IL-6 7 1.8 The proinflammatory cytokines of which interleukin-1 (IL-1), IL-1 IL-6 and tumour necrosis factor-_amp_#x3b1 (TNF-_amp_#x3b1;) TNF-_amp_#x3b1 are involved in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46959 17597167 59384 22551 11892 TNF TNF TNF-A 12 0.3 which interleukin-1 (IL-1), IL-1 IL-6 and tumour necrosis factor-_amp_#x3b1 (TNF-_amp_#x3b1;) TNF-_amp_#x3b1 are involved in the initial immune response help to drive 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46960 17597167 59385 872 583 APC APC APCs 15 0.0 of immunocompetent cells such as lymphocytes and antigen-presenting cells (APCs), APCs that includes stimulation of their production of cytokines chemotactic agents 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46961 17597167 59390 10437 5992 IL1B IL-1 IL-1 4 1.3 In the case of IL-1 there is an endogenous competitive antagonist of IL-1 receptor (IL-1R)-mediated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46962 17597167 59390 10437 5992 IL1B IL-1 IL-1 12 1.3 case of IL-1 there is an endogenous competitive antagonist of IL-1 receptor (IL-1R)-mediated IL-1R -mediated activity IL-1 receptor antagonist (IL-1ra), IL-1ra 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46963 17597167 59390 10444 5993 IL1R1 IL1R IL-1R 14 0.3 there is an endogenous competitive antagonist of IL-1 receptor (IL-1R)-mediated IL-1R -mediated activity IL-1 receptor antagonist (IL-1ra), IL-1ra that binds to 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46964 17597167 59390 10437 5992 IL1B IL-1 IL-1 16 1.3 endogenous competitive antagonist of IL-1 receptor (IL-1R)-mediated IL-1R -mediated activity IL-1 receptor antagonist (IL-1ra), IL-1ra that binds to the receptor without 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46965 17597167 59390 10451 6000 IL1RN IL1RA IL-1ra 19 1.8 IL-1 receptor (IL-1R)-mediated IL-1R -mediated activity IL-1 receptor antagonist (IL-1ra), IL-1ra that binds to the receptor without the association of the 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 46966 17597167 59390 10444 5993 IL1R1 IL1R IL-1R 30 0.3 that binds to the receptor without the association of the IL-1R accessory protein (IL-1RAcP) IL-1RAcP and hence without an ensuing biological 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46967 17597167 59390 10446 5995 IL1RAP IL-1RAcP IL-1RAcP 33 1.3 receptor without the association of the IL-1R accessory protein (IL-1RAcP) IL-1RAcP and hence without an ensuing biological activity (see see 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46968 17597167 59391 10444 5993 IL1R1 IL1R IL-1R 4 0.3 In addition the soluble IL-1R type II (IL-1RII) IL-1RII acts as a so called decoy 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46969 17597167 59391 10437 5992 IL1B IL-1 IL-1 17 1.3 IL-1RII acts as a so called decoy receptor by binding IL-1 and preventing the binding to the signalling type I receptor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46970 17597167 59392 10451 6000 IL1RN IL1RA IL-1ra 8 1.8 The existence of two endogenous inhibitors sIL-1RII and IL-1ra underlines the potency of IL-1 both with regard to the 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 46971 17597167 59392 10437 5992 IL1B IL-1 IL-1 13 1.3 two endogenous inhibitors sIL-1RII and IL-1ra underlines the potency of IL-1 both with regard to the binding affinity and the fact 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46972 17597167 59396 10437 5992 IL1B IL-1 IL-1 3 1.3 Cytokines such as IL-1 also activate the hypothalamo_amp_#x2013 pituitary_amp_#x2013 adrenal (HPA)-axis HPA -axis (see 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46973 17597167 59396 4928 2355 CRH CRF CRF 19 0.6 see 3 resulting in the release of corticotrophin-releasing factor (CRF), CRF adrenocorticotrophic hormone (ACTH) ACTH and corticosterone 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>24182|C1QL1|10882|No_GeneRif__2355|CRH|1392|Complete__<>AvaiableGeneRif=1<> 1 1 2037 24182 C1QL1 0 46974 17597167 59396 16975 9201 POMC ACTH ACTH 22 1.5 the release of corticotrophin-releasing factor (CRF), CRF adrenocorticotrophic hormone (ACTH) ACTH and corticosterone 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46975 17597167 59396 9590 5164 HPSE HPA HPA 8 0.0 such as IL-1 also activate the hypothalamo_amp_#x2013 pituitary_amp_#x2013 adrenal (HPA)-axis HPA -axis (see see 3 resulting in the release of corticotrophin-releasing 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46976 17597167 59398 10437 5992 IL1B IL-1 IL-1 4 1.3 The occurrence of both IL-1 isoforms IL-1_amp_#x3b1 and IL-1_amp_#x3b2 in the adrenal gland constitutively as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46977 17597167 59398 10676 6121 IRF6 LPS LPS 20 0.3 adrenal gland constitutively as well as inducible by lipopolysaccharides (LPS) LPS 4 provides another source of agonists as well as antagonists 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 46978 17597167 59398 10437 5992 IL1B IL-1 IL-1 32 1.3 provides another source of agonists as well as antagonists for IL-1 receptors in a situation when the immune system is activated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46979 17597167 59400 10437 5992 IL1B IL-1 IL-1 1 1.3 Interestingly IL-1 has been shown to exert modulatory effects on learning and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46980 17597167 59401 10437 5992 IL1B IL-1 IL-1 39 1.3 on the habituation in the open field 9 suggesting that IL-1 may be an important modulator of hippocampus-dependent learning 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46981 17597167 59407 9947 5468 IGFALS ALS ALS 28 0.3 as Alzheimer's disease (AD), AD epilepsy amyotrophic lateral sclerosis (ALS) ALS and Parkinson's disease as well as diseases with autoimmune characteristics 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000450260721008533<>ScoreDetail__5468|IGFALS|0.000337695077597634__11179|SOD1|0.000450260721008533__ 0 0 0 0 0 46982 17597167 59408 18723 10261 ROS1 ROS ROS 28 0.0 such as nitric oxide (NO), NO reactive oxygen species (ROS), ROS glutamate quinolinic acid and proteolytic enzymes are thus common features 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46983 17597167 59412 10437 5992 IL1B IL-1 IL-1 3 1.3 Cytokines such as IL-1 and other inflammatory molecules may be causative or protective or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46984 17597167 59413 10437 5992 IL1B IL-1 IL-1 4 1.3 The endogenous antagonist of IL-1 receptors IL-1ra is a useful tool to study the role 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46985 17597167 59413 10451 6000 IL1RN IL1RA IL-1ra 6 1.8 The endogenous antagonist of IL-1 receptors IL-1ra is a useful tool to study the role of IL-1R-mediated 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 46986 17597167 59414 10451 6000 IL1RN IL1RA IL-1ra 1 1.8 Thus IL-1ra provides neuroprotection in different models of cerebral ischaemia upon peripheral 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 46987 17597167 59415 10451 6000 IL1RN IL1RA IL-1ra 2 1.8 Furthermore endogenous IL-1ra was shown to be neuroprotective since inhibition of the action 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 46988 17597167 59415 10451 6000 IL1RN IL1RA IL-1ra 14 1.8 shown to be neuroprotective since inhibition of the action of IL-1ra by passive immunoneutralisation enhanced cerebral damage in permanent focal cerebral 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 46989 17597167 59416 10451 6000 IL1RN IL1RA IL-1ra 0 1.8 IL-1ra exists in three isoforms i.e two intracellular forms (icIL-1ra) icIL-1ra 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 46990 17597167 59417 10451 6000 IL1RN IL1RA IL-1ra 6 1.8 Transgenic overexpression of human soluble (hs) hs IL-1ra (Tg Tg hsIL-1ra in the central nervous system (CNS) CNS 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 46991 17597167 59420 10451 6000 IL1RN IL1RA IL-1ra 22 1.8 a post-ischaemic depletion of hsIL-1ra suggesting that the levels of IL-1ra were insufficient to provide neuroprotection under those circumstances particularly in 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 46992 17597167 59422 10437 5992 IL1B IL-1 IL-1 21 1.3 it is dependent on the degree of central blockade of IL-1 transmission 12 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46993 17597167 59424 10437 5992 IL1B IL-1 IL-1 8 1.3 This conclusion is supported by the fact that IL-1 promotes astroglial proliferation during embryogenesis and that it has immunomodulatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46994 17597167 59426 10437 5992 IL1B IL-1 IL-1 5 1.3 It has been suggested that IL-1 released from amoeboid microglia during development is involved in regulating 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46995 17597167 59427 10437 5992 IL1B IL-1 IL-1 1 1.3 Interestingly IL-1 has been shown to stimulate the differentiation of mesencephalic progenitor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46996 17597167 59429 10463 6018 IL6 IL-6 IL-6 4 1.8 The levels of IL-1_amp_#x3b2 IL-6 and TNF-_amp_#x3b1 in different brain regions of the Tg hsIL-1ra 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46997 17597167 59429 22551 11892 TNF TNF TNF-A 6 0.3 The levels of IL-1_amp_#x3b2 IL-6 and TNF-_amp_#x3b1 in different brain regions of the Tg hsIL-1ra mice were 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46998 17597167 59430 10437 5992 IL1B IL-1 IL-1 11 1.3 these cytokines were essentially unaffected by the chronic blocking of IL-1 receptors in the brain 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46999 17597167 59432 10437 5992 IL1B IL-1 IL-1 5 1.3 Furthermore a modulatory role of IL-1 signalling in the brain on the production of amyloid precursor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47000 17597167 59432 926 620 APP amyloid amyloid 14 1.0 of IL-1 signalling in the brain on the production of amyloid precursor protein (APP) APP was suggested by the finding that 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 47001 17597167 59432 926 620 APP APP APP 17 0.3 the brain on the production of amyloid precursor protein (APP) APP was suggested by the finding that the heterozygotic but not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47002 17597167 59432 926 620 APP APP APP 34 0.3 the heterozygotic but not homozygotic mice had decreased levels of APP in the cerebellum 12 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47003 17597167 59436 11629 6493 LAMC2 CSF CSF 20 0.0 factors in post mortem brain tissue and cerebrospinal fluid (CSF) CSF samples from AD patients represent evidence for an inflammatory reaction 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47004 17597167 59437 10437 5992 IL1B IL-1 IL-1 9 1.3 Experimental studies have shown the reciprocal interactions between cytokines IL-1 and IL-6 and APP/_amp_#x3b2;-amyloid APP _amp_#x3b2 -amyloid (A_amp_#x3b2;) A_amp_#x3b2 peptide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47005 17597167 59437 10463 6018 IL6 IL-6 IL-6 9 1.8 Experimental studies have shown the reciprocal interactions between cytokines IL-1 and IL-6 and APP/_amp_#x3b2;-amyloid APP _amp_#x3b2 -amyloid (A_amp_#x3b2;) A_amp_#x3b2 peptide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47006 17597167 59437 10463 6018 IL6 IL-6 IL-6 11 1.8 studies have shown the reciprocal interactions between cytokines IL-1 and IL-6 and APP/_amp_#x3b2;-amyloid APP _amp_#x3b2 -amyloid (A_amp_#x3b2;) A_amp_#x3b2 peptide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47007 17597167 59437 926 620 APP APP APP 13 0.3 the reciprocal interactions between cytokines IL-1 and IL-6 and APP/_amp_#x3b2;-amyloid APP _amp_#x3b2 -amyloid (A_amp_#x3b2;) A_amp_#x3b2 peptide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47008 17597167 59437 926 620 APP amyloid amyloid 13 1.0 interactions between cytokines IL-1 and IL-6 and APP/_amp_#x3b2;-amyloid APP _amp_#x3b2 -amyloid (A_amp_#x3b2;) A_amp_#x3b2 peptide 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 47009 17597167 59438 926 620 APP APP APP 9 0.3 Thus the cytokines stimulate synthesis release and metabolism of APP 28 and 29 while the cleavage product A_amp_#x3b2 peptide induces 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47010 17597167 59439 10463 6018 IL6 IL-6 IL-6 26 1.8 mouse models of AD exemplified by the early expression of IL-6 mRNA prior to the appearance of amyloid plaques in mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47011 17597167 59439 926 620 APP amyloid amyloid 33 1.0 early expression of IL-6 mRNA prior to the appearance of amyloid plaques in mice with overexpression of human APP with the 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 47012 17597167 59439 926 620 APP APP APP 41 0.3 appearance of amyloid plaques in mice with overexpression of human APP with the so called Swedish mutation 31 and gliosis in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47013 17597167 59439 912 613 APOE APOE apoE 53 0.3 so called Swedish mutation 31 and gliosis in apolipoprotein (apoE) apoE knock-out mice 32 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47014 17597167 59442 353 245 ADD3 ADDL ADDLs 15 0.0 indicate that A_amp_#x3b2 oligomers or A_amp_#x3b2 -derived diffusible ligands (ADDLs), ADDLs may interfere with synaptic transmission and cause neurotoxicity 33 34 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47015 17597167 59443 9905 5438 IFNG IFN IFN-G 19 0.0 1_amp_#x2013 42 stimulated an increased release of the inflammatory cytokines IFN-_amp_#x3b3 IL-1_amp_#x3b1 and IL-1_amp_#x3b2 30 may support the involvement of these 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.00050621058468952<>ScoreDetail__5438|IFNG|0.000402004662223399__5417|IFNA1|0.00050621058468952__ 0 0 0 0 0 47016 17597167 59444 10437 5992 IL1B IL-1 IL-1 46 1.3 an attempt of the brain to modulate effects of increased IL-1 levels 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47017 17597167 59444 11629 6493 LAMC2 CSF CSF 5 0.0 The levels of sIL-1RII in CSF were increased in AD patients with moderate cognitive dysfunction 37 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47018 17597167 59453 10437 5992 IL1B IL-1 IL-1 14 1.3 hybridisation histochemistry demonstrated that in addition to the proinflammatory cytokine IL-1 the excitotoxic injury is accompanied by an induction of a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47019 17597167 59453 10451 6000 IL1RN IL1RA IL-1ra 33 1.8 of a cytokine with antiinflammatory properties the endogenous receptor antagonist IL-1ra (see see 41 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 47020 17597167 59454 10437 5992 IL1B IL-1 IL-1 16 1.3 of the secreted form sIL-1ra 42 thus available for blocking IL-1 binding to the signalling IL-1RI 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47021 17597167 59455 10451 6000 IL1RN IL1RA IL-1ra 3 1.8 The expression of IL-1ra mRNA and protein ( 42 see 41 was predominantly seen 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 47022 17597167 59456 10451 6000 IL1RN IL1RA IL-1ra 13 1.8 showed that the proinflammatory cytokine IL-1_amp_#x3b2 preceded both the antiinflammatory IL-1ra and the synthesising enzyme caspase-1 (see see 41 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 47023 17597167 59457 3525 1499 CASP1 ICE ICE 4 0.3 Caspase-1 or IL-1_amp_#x3b2 -converting enzyme (ICE), ICE is one of several cystein proteases that cleave the substrate 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47024 17597167 59460 16975 9201 POMC MSH MSH 27 1.5 Fig 2 co-localised with _amp_#x3b1 -melanocyte stimulating hormone (_amp_#x3b1;-MSH) _amp_#x3b1 -MSH 45 whereas both IL-1ra and IL-1RI were found to be 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47025 17597167 59460 10451 6000 IL1RN IL1RA IL-1ra 32 1.8 _amp_#x3b1 -melanocyte stimulating hormone (_amp_#x3b1;-MSH) _amp_#x3b1 -MSH 45 whereas both IL-1ra and IL-1RI were found to be expressed in vasopressin neurons 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 47026 17597167 59461 9659 18646 HSD17B12 KAR KA-receptor 18 0.0 systemic administration of KA is mediated not only by the KA-receptor subtype of glutamate receptors but also indirectly by the release 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47027 17597167 59462 10451 6000 IL1RN IL1RA IL-1ra 15 1.8 and (R)-CPP R -CPP reduced KA-induced expression of IL-1_amp_#x3b2 and IL-1ra 47 indicating that this microglial response to KA is due 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 47028 17597167 59462 4877 2322 CPP CPP CPP 8 0.0 fact the NMDA-receptor antagonists MK-801 (dizocilpine) dizocilpine and (R)-CPP R -CPP reduced KA-induced expression of IL-1_amp_#x3b2 and IL-1ra 47 indicating that 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47029 17597167 59467 10451 6000 IL1RN IL1RA IL-1ra 10 1.8 The ratios between the levels of IL-1_amp_#x3b2 and those of IL-1ra and IL-6 respectively in response to KA changed over time 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 47030 17597167 59467 10463 6018 IL6 IL-6 IL-6 12 1.8 between the levels of IL-1_amp_#x3b2 and those of IL-1ra and IL-6 respectively in response to KA changed over time in such 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47031 17597167 59471 10451 6000 IL1RN IL1RA IL-1ra 3 1.8 The levels of IL-1ra in the hippocampus were still elevated at 24_amp_#xa0 h ( 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 47032 17597167 59472 10451 6000 IL1RN IL1RA IL-1ra 16 1.8 seems reasonable to hypothesise that the balance between IL-1_amp_#x3b2 and IL-1ra and possibly other cytokines in the hypothalamus has consequences for 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 47033 17597167 59474 10437 5992 IL1B IL-1 IL-1 14 1.3 have inhibitory effects on immune responses and the synthesis of IL-1 1 have been shown to block KA-induced IL-1_amp_#x3b2 mRNA expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47034 17597167 59475 10451 6000 IL1RN IL1RA IL-1ra 8 1.8 Together with the finding that i.c.v administration of IL-1ra protects against the pro-epileptogenic effect of IL-1_amp_#x3b2 15 without affecting 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 47035 17597167 59476 16975 9201 POMC MSH MSH 2 1.5 The neuropeptide _amp_#x3b1 -MSH is known to have anti-pyretic and antiinflammatory properties (see see 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47036 17597167 59477 16975 9201 POMC MSH MSH 2 1.5 Co-administration of _amp_#x3b1 -MSH and KA in rats showed a potentiating effect of _amp_#x3b1 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47037 17597167 59477 16975 9201 POMC MSH MSH 12 1.5 and KA in rats showed a potentiating effect of _amp_#x3b1 -MSH on KA-induced hyperthermia as well as on the initial KA-induced 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47038 17597167 59477 16975 9201 POMC MSH MSH 26 1.5 well as on the initial KA-induced hypothermic effect whereas _amp_#x3b1 -MSH administered alone produced a dose-dependent increase in core temperature with 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47039 17597167 59478 16975 9201 POMC MSH MSH 28 1.5 42 47 51 and 53 see 41 and that _amp_#x3b1 -MSH has been shown to reduce the levels of IL-1 and 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47040 17597167 59478 10437 5992 IL1B IL-1 IL-1 37 1.3 _amp_#x3b1 -MSH has been shown to reduce the levels of IL-1 and other pyrogenic proinflammatory cytokines (see see 55 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47041 17597167 59479 16975 9201 POMC MSH MSH 19 1.5 modulation of core temperature changes by KA 50 and _amp_#x3b1 -MSH respectively indicates the complexity of temperature regulation 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47042 17597167 59480 16975 9201 POMC MSH MSH 5 1.5 A more consistent effect of _amp_#x3b1 -MSH on body temperature was observed in global cerebral ischaemia in 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47043 17597167 59481 16975 9201 POMC MSH MSH 3 1.5 Thus pretreatment with _amp_#x3b1 -MSH resulted in a hypothermic response with continued decrease during the 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47044 17597167 59482 16975 9201 POMC MSH MSH 5 1.5 In addition systemic administration of _amp_#x3b1 -MSH was found to potentiate the decrease in brain temperature observed 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47045 17597167 59483 16975 9201 POMC MSH MSH 5 1.5 Several studies have shown that _amp_#x3b1 -MSH can provide protection against tissue damage due to ischaemia in 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47046 17597167 59483 16975 9201 POMC MSH MSH 57 1.5 and reperfusion in the rat upon peripheral administration of _amp_#x3b1 -MSH 62 and in the Mongolian gerbil upon administration of a 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47047 17597167 59484 16975 9201 POMC MSH MSH 8 1.5 Thus we found that upon post-ischaemic administration of _amp_#x3b1 -MSH there was a 75% larger number of viable neurons in 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47048 17597167 59484 3353 1368 CA1 CA1 CA1 21 0.0 a 75% larger number of viable neurons in the hippocampal CA1 pyramidal cell layer as compared to saline-treated rats 62 ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47049 17597167 59485 16975 9201 POMC MSH MSH 5 1.5 Neuroprotective and neurotrophic activities of _amp_#x3b1 -MSH have also been shown in various models of neuronal injury 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47050 17597167 59486 16975 9201 POMC MSH MSH 5 1.5 Recently we have found that _amp_#x3b1 -MSH may provide neuroprotection also upon KA-induced excitotoxicity 65 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47051 17597167 59487 16975 9201 POMC MSH MSH 5 1.5 Also in this case was _amp_#x3b1 -MSH administered after the toxic insult and the rescuing effect seen 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47052 17597167 59487 3353 1368 CA1 CA1 CA1 21 0.0 and the rescuing effect seen by stereological analysis of the CA1 pyramidal cell layer 65 was accompanied by a reduction in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47053 17597167 59488 16975 9201 POMC MSH MSH 8 1.5 It is conceivable that the antiinflammatory properties of _amp_#x3b1 -MSH are responsible for its neuroprotective activities but other properties such 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47054 17597167 59488 1624 1033 BDNF BDNF BDNF 28 1.9 such as neurotrophic actions via e.g brain-derived neurotrophic factor (BDNF) BDNF or vascular effects may also be considered 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47055 17597167 59495 10451 6000 IL1RN IL1RA IL-1ra 2 1.8 Homozygotic (Tg Tg IL-1ra +/+ n = 12 mice spent significantly longer time in 11 JUMiner_v2.2 1 0 0 2 6000 TotalCon:2<>5993|IL1R1|3554|Complete__6000|IL1RN|3557|Complete__<>AvaiableGeneRif=2<>BEST:6000|IL1RN|0.000344283989942882<>ScoreDetail__5993|IL1R1|0.00027457028305595__6000|IL1RN|0.000344283989942882__ 0 0 0 0 0 47056 17597167 59498 6852 17944 EXOSC3 p10 p10 14 0.3 of the rat hypothalamus after incubation with antibodies to the p10 subunit of caspase-1 showing immunoreactive nerve cell bodies in the 1 JUMiner_v2.2 1 0 0 2 10487 TotalCon:2<>17944|EXOSC3|51010|Complete__10487|S100A10|6281|Complete__<>AvaiableGeneRif=2<>BEST:10487|S100A10|0.000511793549702374<>ScoreDetail__10487|S100A10|0.000511793549702374__17944|EXOSC3|0.000212059093800806__ 0 0 0 0 0 47057 17597167 59502 16975 9201 POMC MSH MSH 19 1.5 during global cerebral ischaemia in rats following pretreatment with _amp_#x3b1 -MSH ( n = 7 but not saline ( n = 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47058 17597167 59503 16975 9201 POMC MSH MSH 15 1.5 during cerebral ischaemia is larger in rats pretreated with _amp_#x3b1 -MSH than after saline pretreatment ( p _amp_#x3c 0.05 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47059 17597167 59506 16975 9201 POMC MSH MSH 36 1.5 cerebral ischaemia/reperfusion ischaemia reperfusion followed by systemic administration of _amp_#x3b1 -MSH 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 47060 17597167 59506 3353 1368 CA1 CA1 CA1 14 0.0 violet-stained sections of the rat hippocampus showing part of the CA1 pyramidal cell layer after (A) A sham surgery (B) B 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 47061 17597167 59508 16975 9201 POMC MSH MSH 9 1.5 Note the marked protection provided by post-ischaemic administration of _amp_#x3b1 -MSH (C) C 11 JUMiner_v2.2 1 0 0 2 9201 TotalCon:2<>7392|MSX2|4488|Complete__9201|POMC|5443|Complete__<>AvaiableGeneRif=2<>BEST:9201|POMC|0.000456932283487153<>ScoreDetail__9201|POMC|0.000456932283487153__7392|MSX2|0.000387238345201472__ 0 0 0 0 0 51654 17678953 64372 18723 10261 ROS1 ROS ROS 14 0.0 as nitric oxide (NO) NO and reactive oxygen species (ROS), ROS can contribute to neurodegenerative diseases in part by triggering protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 51655 17678953 64374 20996 11179 SOD1 ALS ALS 39 0.0 ranging from Parkinson's disease (PD), PD amyotrophic lateral sclerosis (ALS), ALS multiple sclerosis and Alzheimer's disease (AD) AD to stroke and 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000568982184781108<>ScoreDetail__5468|IGFALS|0.000370578326782706__11179|SOD1|0.000568982184781108__ 0 0 0 0 0 51656 17678953 64375 18723 10261 ROS1 ROS ROS 36 0.0 ion channel and subsequent free radical production including NO and ROS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 51657 17678953 64378 16327 14180 PDIA2 PDI PDI 8 1.5 One such molecule affected is protein disulfide isomerase (PDI), PDI an enzyme responsible for normal protein folding in the endoplasmic 1 JUMiner_v2.2 1 0 0 2 8548 TotalCon:3<>8548|P4HB|5034|Complete__18367|PADI1|29943|Complete__14180|PDIA2|64714|Complete__<>AvaiableGeneRif=3<>BEST:8548|P4HB|0.00148003894839338<>ScoreDetail__14180|PDIA2|0.000527065527065527__18367|PADI1|0.000269230769230769__8548|P4HB|0.00148003894839338__ 0 0 0 0 0 51658 17678953 64379 16327 14180 PDIA2 PDI PDI 4 1.5 We found that when PDI is S-nitrosylation (forming forming SNO-PDI the function of the enzyme 1 JUMiner_v2.2 1 0 0 2 8548 TotalCon:3<>8548|P4HB|5034|Complete__18367|PADI1|29943|Complete__14180|PDIA2|64714|Complete__<>AvaiableGeneRif=3<>BEST:8548|P4HB|0.00148003894839338<>ScoreDetail__14180|PDIA2|0.000527065527065527__18367|PADI1|0.000269230769230769__8548|P4HB|0.00148003894839338__ 0 0 0 0 0 51659 17678953 64388 1442 905 AXL UFO UFO 9 0.0 these Uncompetitive/Fast Uncompetitive Fast Off-rate therapeutics we use the term UFO drugs because like Unidentified Flying Objects they leave very quickly 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 51660 17678953 64395 16327 14180 PDIA2 PDI PDI 6 1.5 In this case in contrast to PDI or parkin S-nitrosylation proves to be neuroprotective by decreasing excessive 1 JUMiner_v2.2 1 0 0 2 8548 TotalCon:3<>8548|P4HB|5034|Complete__18367|PADI1|29943|Complete__14180|PDIA2|64714|Complete__<>AvaiableGeneRif=3<>BEST:8548|P4HB|0.00148003894839338<>ScoreDetail__14180|PDIA2|0.000527065527065527__18367|PADI1|0.000269230769230769__8548|P4HB|0.00148003894839338__ 0 0 0 0 0 51661 17678953 64396 1442 905 AXL UFO UFO 16 0.0 can be achieved by coupling NO to memantine yielding second-generation UFO drugs known as NitroMemantines 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43598 17852013 55124 3766 10632 CCL5 RANTES RANTES 0 2.1 RANTES levels are elevated in serum and cerebrospinal fluid in patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43599 17852013 55125 20996 11179 SOD1 ALS ALS 12 0.0 been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00124340580038119<>ScoreDetail__5468|IGFALS|0.0011449835408616__11179|SOD1|0.00124340580038119__ 0 0 0 0 0 43600 17852013 55127 3766 10632 CCL5 RANTES RANTES 8 2.1 Regulated upon activation normal T-cell expressed and secreted (RANTES) RANTES is a C-C beta-chemokine with strong chemo-attractant activity for T-lymphocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43601 17852013 55127 10471 6026 IL8RA C-C C-C 11 0.0 activation normal T-cell expressed and secreted (RANTES) RANTES is a C-C beta-chemokine with strong chemo-attractant activity for T-lymphocytes and monocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43602 17852013 55128 3766 10632 CCL5 RANTES RANTES 5 2.1 We examined serum levels of RANTES in 20 patients with amyotrophic lateral sclerosis (ALS), ALS 14 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43603 17852013 55128 3766 10632 CCL5 RANTES RANTES 32 2.1 subjects (CTRL) CTRL and cerebrospinal fluid (CSF) CSF levels of RANTES in ALS and NIND group patients in order to investigate 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43604 17852013 55128 3766 10632 CCL5 RANTES RANTES 44 2.1 ALS and NIND group patients in order to investigate whether RANTES as index of immune activation is present in ALS patients 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43605 17852013 55128 20996 11179 SOD1 ALS ALS 13 0.0 of RANTES in 20 patients with amyotrophic lateral sclerosis (ALS), ALS 14 patients with non-inflammatory neurological disorders (NIND) NIND and 13 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00124340580038119<>ScoreDetail__5468|IGFALS|0.0011449835408616__11179|SOD1|0.00124340580038119__ 0 0 0 0 0 43606 17852013 55128 5131 2524 CTRL CTRL CTRL 25 0.0 non-inflammatory neurological disorders (NIND) NIND and 13 control subjects (CTRL) CTRL and cerebrospinal fluid (CSF) CSF levels of RANTES in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43607 17852013 55128 11629 6493 LAMC2 CSF CSF 29 0.0 and 13 control subjects (CTRL) CTRL and cerebrospinal fluid (CSF) CSF levels of RANTES in ALS and NIND group patients in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43608 17852013 55128 20996 11179 SOD1 ALS ALS 34 0.1 CTRL and cerebrospinal fluid (CSF) CSF levels of RANTES in ALS and NIND group patients in order to investigate whether RANTES 6 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00124340580038119<>ScoreDetail__5468|IGFALS|0.0011449835408616__11179|SOD1|0.00124340580038119__ 0 0 0 0 0 43609 17852013 55128 20996 11179 SOD1 ALS ALS 53 0.0 whether RANTES as index of immune activation is present in ALS patients 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00124340580038119<>ScoreDetail__5468|IGFALS|0.0011449835408616__11179|SOD1|0.00124340580038119__ 0 0 0 0 0 43610 17852013 55129 3766 10632 CCL5 RANTES RANTES 5 2.1 Patients with ALS had higher RANTES levels compared with the NIND patients and CTRL subjects (p 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43611 17852013 55129 20996 11179 SOD1 ALS ALS 2 0.0 Patients with ALS had higher RANTES levels compared with the NIND patients and 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00124340580038119<>ScoreDetail__5468|IGFALS|0.0011449835408616__11179|SOD1|0.00124340580038119__ 0 0 0 0 0 43612 17852013 55129 5131 2524 CTRL CTRL CTRL 13 0.0 had higher RANTES levels compared with the NIND patients and CTRL subjects (p p = 0.005 and p = 0.02 respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43613 17852013 55130 3766 10632 CCL5 RANTES RANTES 1 2.1 CSF RANTES levels were also higher compared with the NIND patients (p 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43614 17852013 55130 11629 6493 LAMC2 CSF CSF 0 0.2 CSF RANTES levels were also higher compared with the NIND patients 5 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 43615 17852013 55131 3766 10632 CCL5 RANTES RANTES 6 2.1 No correlation of serum and CSF RANTES levels with disease duration was found 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43616 17852013 55131 11629 6493 LAMC2 CSF CSF 5 0.2 No correlation of serum and CSF RANTES levels with disease duration was found 5 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 43617 17852013 55132 20996 11179 SOD1 ALS ALS 18 0.0 recruitment of peripheral inflammatory cells to sites of inflammation in ALS patients 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00124340580038119<>ScoreDetail__5468|IGFALS|0.0011449835408616__11179|SOD1|0.00124340580038119__ 0 0 0 0 0 43674 17853944 55213 20996 11179 SOD1 ALS ALS 4 2.2 Abstract Amyotrophic lateral sclerosis (ALS), ALS one of the most common adult-onset neurodegenerative diseases has no 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43675 17853944 55214 20996 11179 SOD1 ALS ALS 12 2.2 stress and inflammation have been associated with the pathoprogression of ALS through a poorly defined mechanism 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43676 17853944 55215 20996 11179 SOD1 ALS ALS 8 2.2 Here we determined that dysregulated redox stress in ALS mice caused by NADPH oxidases Nox1 and Nox2 significantly influenced 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43677 17853944 55215 14551 7889 NOX1 NOX1 Nox1 14 4.2 dysregulated redox stress in ALS mice caused by NADPH oxidases Nox1 and Nox2 significantly influenced the progression of motor neuron disease 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43678 17853944 55215 5281 2578 CYBB NOX2 NOX2 14 7.1 dysregulated redox stress in ALS mice caused by NADPH oxidases Nox1 and Nox2 significantly influenced the progression of motor neuron disease 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43679 17853944 55215 5281 2578 CYBB NOX2 Nox2 16 7.1 stress in ALS mice caused by NADPH oxidases Nox1 and Nox2 significantly influenced the progression of motor neuron disease caused by 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43680 17853944 55215 20996 11179 SOD1 SOD1 SOD1 28 3.9 influenced the progression of motor neuron disease caused by mutant SOD1 G93A expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43681 17853944 55217 5281 2578 CYBB NOX2 Nox2 9 7.1 However 50% survival rates were enhanced significantly more by Nox2 deletion than by Nox1 deletion 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43682 17853944 55217 14551 7889 NOX1 NOX1 Nox1 13 4.2 rates were enhanced significantly more by Nox2 deletion than by Nox1 deletion 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43683 17853944 55218 20996 11179 SOD1 ALS ALS 2 2.2 Interestingly female ALS mice containing only 1 active X-linked Nox1 or Nox2 gene 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43684 17853944 55218 14551 7889 NOX1 NOX1 Nox1 9 4.2 Interestingly female ALS mice containing only 1 active X-linked Nox1 or Nox2 gene also had significantly delayed disease onset but 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43685 17853944 55218 5281 2578 CYBB NOX2 Nox2 11 7.1 female ALS mice containing only 1 active X-linked Nox1 or Nox2 gene also had significantly delayed disease onset but showed normal 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43686 17853944 55219 5281 2578 CYBB NOX2 Nox2 6 7.1 Nox activity in spinal cords from Nox2 heterozygous female ALS mice was approximately 50% that of WT 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43687 17853944 55219 20996 11179 SOD1 ALS ALS 9 2.2 Nox activity in spinal cords from Nox2 heterozygous female ALS mice was approximately 50% that of WT female ALS mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43688 17853944 55219 20996 11179 SOD1 ALS ALS 18 2.2 female ALS mice was approximately 50% that of WT female ALS mice suggesting that random X-inactivation was not influenced by Nox2 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43689 17853944 55219 5281 2578 CYBB NOX2 Nox2 28 7.1 ALS mice suggesting that random X-inactivation was not influenced by Nox2 gene deletion 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43690 17853944 55220 20996 11179 SOD1 ALS ALS 19 2.2 spinal cord significantly delayed onset of motor neuron disease in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43691 17853944 55221 20996 11179 SOD1 ALS ALS 15 2.2 believe to be new modifier gene targets for treatment of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43692 17853944 55223 20996 11179 SOD1 ALS ALS 3 2.2 Amyotrophic lateral sclerosis (ALS) ALS is a fatal neurodegenerative disease that can be caused by 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43693 17853944 55223 20996 11179 SOD1 SOD1 SOD1 19 3.9 can be caused by dominant mutations in superoxide dismutase-1 (SOD1) SOD1 ( 1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43694 17853944 55224 20996 11179 SOD1 ALS ALS 13 2.2 as to the precise mechanism of motor neuron death in ALS although oxidative stress and inflammation are both believed to be 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43695 17853944 55225 20996 11179 SOD1 SOD1 SOD1 7 3.9 Transgenic mice overexpressing a mutant form of SOD1 found in ALS patients (SOD1 SOD1 G93A develop motor neuron 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43696 17853944 55225 20996 11179 SOD1 ALS ALS 10 2.2 Transgenic mice overexpressing a mutant form of SOD1 found in ALS patients (SOD1 SOD1 G93A develop motor neuron disease similar to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43697 17853944 55225 20996 11179 SOD1 SOD1 SOD1 12 3.9 a mutant form of SOD1 found in ALS patients (SOD1 SOD1 G93A develop motor neuron disease similar to that seen clinically 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43698 17853944 55225 20996 11179 SOD1 ALS ALS 28 2.2 disease similar to that seen clinically in familial forms of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43699 17853944 55226 20996 11179 SOD1 SOD1 SOD1 7 3.9 Recent studies using conditional reduction of mutant SOD1 in either motor neurons or glia of mice have suggested 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43700 17853944 55227 20996 11179 SOD1 SOD1 SOD1 13 3.9 transplants or chimeric animals other studies have demonstrated that mutant SOD1 expression in microglia leads to neuronal toxicity ( 5 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43701 17853944 55227 20996 11179 SOD1 SOD1 SOD1 31 3.9 toxicity ( 5 and that non-neuronal cells lacking the mutant SOD1 protein can protect from disease ( 6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43702 17853944 55229 20996 11179 SOD1 ALS ALS 13 2.2 thought to be an important component of disease progression in ALS ( 3 7 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43703 17853944 55230 20996 11179 SOD1 SOD1 SOD1 6 3.9 Indeed recent studies have shown that SOD1 G93A ALS transgenic mice produce elevated levels of Nox2 gp91phox 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43704 17853944 55230 20996 11179 SOD1 ALS ALS 8 2.2 Indeed recent studies have shown that SOD1 G93A ALS transgenic mice produce elevated levels of Nox2 gp91phox and superoxide 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43705 17853944 55230 5281 2578 CYBB NOX2 Nox2 15 7.1 that SOD1 G93A ALS transgenic mice produce elevated levels of Nox2 gp91phox and superoxide in spinal cord microglia ( 8 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43706 17853944 55230 5281 2578 CYBB GP91PHOX gp91phox 16 2.0 SOD1 G93A ALS transgenic mice produce elevated levels of Nox2 gp91phox and superoxide in spinal cord microglia ( 8 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43707 17853944 55232 14551 7889 NOX1 NOX1 Nox1 4 4.2 Seven known NADPH oxidases (Nox1, Nox1 Nox2 Nox3 Nox4 Nox5 Duox1 and Duox2 are thought to 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43708 17853944 55232 5281 2578 CYBB NOX2 Nox2 5 7.1 Seven known NADPH oxidases (Nox1, Nox1 Nox2 Nox3 Nox4 Nox5 Duox1 and Duox2 are thought to play 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43709 17853944 55232 14552 7890 NOX3 NOX3 Nox3 6 0.9 Seven known NADPH oxidases (Nox1, Nox1 Nox2 Nox3 Nox4 Nox5 Duox1 and Duox2 are thought to play important 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43710 17853944 55232 14553 7891 NOX4 NOX4 Nox4 7 0.9 Seven known NADPH oxidases (Nox1, Nox1 Nox2 Nox3 Nox4 Nox5 Duox1 and Duox2 are thought to play important roles 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43711 17853944 55232 14554 14874 NOX5 NOX5 Nox5 8 0.9 Seven known NADPH oxidases (Nox1, Nox1 Nox2 Nox3 Nox4 Nox5 Duox1 and Duox2 are thought to play important roles in 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43712 17853944 55232 6192 3062 DUOX1 DUOX1 Duox1 9 0.3 Seven known NADPH oxidases (Nox1, Nox1 Nox2 Nox3 Nox4 Nox5 Duox1 and Duox2 are thought to play important roles in redox-dependent 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43713 17853944 55232 6193 13273 DUOX2 DUOX2 DUOX2 9 0.3 Seven known NADPH oxidases (Nox1, Nox1 Nox2 Nox3 Nox4 Nox5 Duox1 and Duox2 are thought to play important roles in redox-dependent 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43714 17853944 55232 6193 13273 DUOX2 DUOX2 Duox2 11 0.3 NADPH oxidases (Nox1, Nox1 Nox2 Nox3 Nox4 Nox5 Duox1 and Duox2 are thought to play important roles in redox-dependent cell signaling 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43715 17853944 55233 5281 2578 CYBB NOX2 Nox2 1 7.1 Although Nox2 expression increases in microglia of the spinal cord of SOD1 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43716 17853944 55233 20996 11179 SOD1 SOD1 SOD1 11 3.9 Nox2 expression increases in microglia of the spinal cord of SOD1 G93A transgenic mice deletion of Nox2 on a C57BL/6J C57BL 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43717 17853944 55233 5281 2578 CYBB NOX2 Nox2 17 7.1 the spinal cord of SOD1 G93A transgenic mice deletion of Nox2 on a C57BL/6J C57BL 6J inbred background of SOD1 G93A 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43718 17853944 55233 20996 11179 SOD1 SOD1 SOD1 24 3.9 of Nox2 on a C57BL/6J C57BL 6J inbred background of SOD1 G93A transgenic mice led to only a marginal increase in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43719 17853944 55234 20996 11179 SOD1 ALS ALS 15 2.2 other Nox genes may more significantly influence redox stress in ALS disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43720 17853944 55235 14551 7889 NOX1 NOX1 Nox1 0 4.2 Nox1 and Nox2 are closely related homologs in the Nox gene 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43721 17853944 55235 5281 2578 CYBB NOX2 NOX2 0 7.1 Nox1 and Nox2 are closely related homologs in the Nox gene 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43722 17853944 55235 5281 2578 CYBB NOX2 Nox2 2 7.1 Nox1 and Nox2 are closely related homologs in the Nox gene family and 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43723 17853944 55235 17864 9801 RAC1 RAC1 Rac1 24 0.0 many of the same regulatory characteristics including a requirement for Rac1 and p22 phox coactivators ( 10 _amp_#x02013 12 2 JUMiner_v2.2 1 1 rac1; 0 0 0 0 0 0 0 0 43724 17853944 55235 6257 2961 DYNC1H1 p22 p22 26 0.0 the same regulatory characteristics including a requirement for Rac1 and p22 phox coactivators ( 10 _amp_#x02013 12 1 JUMiner_v2.2 1 1 p22; 0 2 30306 TotalCon:2<>2961|DYNC1H1|1778|Complete__30306|PHB2|11331|Complete__<>AvaiableGeneRif=2<>BEST:30306|PHB2|0.000300120048019208<>ScoreDetail__2961|DYNC1H1|0.000153061224489796__30306|PHB2|0.000300120048019208__ 0 0 0 0 0 43725 17853944 55236 5281 2578 CYBB NOX2 Nox2 10 7.1 To this end we performed studies comparing the contribution of Nox2 or Nox1 deletion on disease progression in mixed hybrid SOD1 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43726 17853944 55236 14551 7889 NOX1 NOX1 Nox1 12 4.2 end we performed studies comparing the contribution of Nox2 or Nox1 deletion on disease progression in mixed hybrid SOD1 G93A ALS 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43727 17853944 55236 20996 11179 SOD1 SOD1 SOD1 20 3.9 Nox2 or Nox1 deletion on disease progression in mixed hybrid SOD1 G93A ALS mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43728 17853944 55236 20996 11179 SOD1 ALS ALS 22 2.2 Nox1 deletion on disease progression in mixed hybrid SOD1 G93A ALS mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43729 17853944 55237 20202 10964 SLC22A18 HET HET 32 0.6 Y and female (WT, WT Nox X+/X+ X X heterozygous HET Nox X+/X_amp_#x02013; X X_amp_#x02013 and KO Nox X_amp_#x02013;/X_amp_#x02013; X_amp_#x02013 X_amp_#x02013 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43730 17853944 55237 20996 11179 SOD1 SOD1 SOD1 44 3.9 X_amp_#x02013 and KO Nox X_amp_#x02013;/X_amp_#x02013; X_amp_#x02013 X_amp_#x02013 mice on the SOD1 G93A transgenic background using siblings from F2 generations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43731 17853944 55239 14551 7889 NOX1 NOX1 Nox1 12 4.2 show that disrupting either of these NADPH oxidase genes ( Nox1 or Nox2 significantly delayed the progression of motor neuron disease 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43732 17853944 55239 5281 2578 CYBB NOX2 Nox2 14 7.1 disrupting either of these NADPH oxidase genes ( Nox1 or Nox2 significantly delayed the progression of motor neuron disease in a 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43733 17853944 55239 20996 11179 SOD1 SOD1 SOD1 26 3.9 significantly delayed the progression of motor neuron disease in a SOD1 G93A transgenic mouse model of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43734 17853944 55239 20996 11179 SOD1 ALS ALS 32 2.2 neuron disease in a SOD1 G93A transgenic mouse model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43735 17853944 55240 20996 11179 SOD1 ALS ALS 2 2.2 Interestingly female ALS mice lacking a single copy of the X-chromosomal Nox1 or 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43736 17853944 55240 14551 7889 NOX1 NOX1 Nox1 11 4.2 female ALS mice lacking a single copy of the X-chromosomal Nox1 or Nox2 genes also exhibited significantly increased survival rates 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43737 17853944 55240 5281 2578 CYBB NOX2 Nox2 13 7.1 mice lacking a single copy of the X-chromosomal Nox1 or Nox2 genes also exhibited significantly increased survival rates 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43738 17853944 55241 14551 7889 NOX1 NOX1 Nox1 14 4.2 in the setting of random X-inactivation a 50% reduction in Nox1 - or Nox2 -expressing cells has a substantial therapeutic benefit 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43739 17853944 55241 5281 2578 CYBB NOX2 Nox2 17 7.1 of random X-inactivation a 50% reduction in Nox1 - or Nox2 -expressing cells has a substantial therapeutic benefit in ALS mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43740 17853944 55241 20996 11179 SOD1 ALS ALS 26 2.2 or Nox2 -expressing cells has a substantial therapeutic benefit in ALS mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43741 17853944 55242 20996 11179 SOD1 ALS ALS 14 2.2 multiple Nox genes appear to contribute to the pathoprogression of ALS and expand potential therapeutic targets for this disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43742 17853944 55246 20996 11179 SOD1 SOD1 SOD1 6 3.9 (a) a Transgenic mice overexpressing the human SOD1 G93A mutant ( 22 were used as a model of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43743 17853944 55246 20996 11179 SOD1 ALS ALS 18 2.2 G93A mutant ( 22 were used as a model of ALS strain name B6SJL-Tg( B6SJL-Tg SOD1 G93A )1Gur/J; 1Gur J stock 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43744 17853944 55246 20996 11179 SOD1 SOD1 SOD1 22 3.9 used as a model of ALS strain name B6SJL-Tg( B6SJL-Tg SOD1 G93A )1Gur/J; 1Gur J stock no 002726 The Jackson Laboratory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43745 17853944 55249 5281 2578 CYBB NOX2 Nox2 1 7.1 (b) b Nox2 gp91phox KO mice ( 23 were also obtained from The 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43746 17853944 55249 5281 2578 CYBB GP91PHOX gp91phox 2 2.0 (b) b Nox2 gp91phox KO mice ( 23 were also obtained from The Jackson 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43747 17853944 55250 14551 7889 NOX1 NOX1 Nox1 1 4.2 (c) c Nox1 KO mice ( 24 were a kind gift from K.H 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43748 17853944 55252 20996 11179 SOD1 SOD1 SOD1 3 3.9 The generation of SOD1 G93A transgenic mice on the Nox2 -KO or Nox1 -KO 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43749 17853944 55252 5281 2578 CYBB NOX2 Nox2 9 7.1 The generation of SOD1 G93A transgenic mice on the Nox2 -KO or Nox1 -KO backgrounds were achieved using the following 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43750 17853944 55252 14551 7889 NOX1 NOX1 Nox1 12 4.2 of SOD1 G93A transgenic mice on the Nox2 -KO or Nox1 -KO backgrounds were achieved using the following breeding scheme 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43751 17853944 55253 5281 2578 CYBB NOX2 Nox2 2 7.1 Because both Nox2 and Nox1 genes are on the X chromosome 2 rounds 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43752 17853944 55253 14551 7889 NOX1 NOX1 NOX1 2 4.2 Because both Nox2 and Nox1 genes are on the X chromosome 2 rounds 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43753 17853944 55253 14551 7889 NOX1 NOX1 Nox1 4 4.2 Because both Nox2 and Nox1 genes are on the X chromosome 2 rounds of breeding 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43754 17853944 55253 20202 10964 SLC22A18 HET HET 27 0.6 to obtain all possible genotypes in each sex ( Nox -HET males were the only genotype not attainable 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43755 17853944 55254 20996 11179 SOD1 SOD1 SOD1 1 3.9 Hemizygous SOD1 G93A transgenic males were bred to Nox2 _amp_#x02013;/_amp_#x02013; _amp_#x02013 _amp_#x02013 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43756 17853944 55254 5281 2578 CYBB NOX2 Nox2 8 7.1 Hemizygous SOD1 G93A transgenic males were bred to Nox2 _amp_#x02013;/_amp_#x02013; _amp_#x02013 _amp_#x02013 or Nox1 _amp_#x02013;/_amp_#x02013; _amp_#x02013 _amp_#x02013 females 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43757 17853944 55254 14551 7889 NOX1 NOX1 Nox1 11 4.2 transgenic males were bred to Nox2 _amp_#x02013;/_amp_#x02013; _amp_#x02013 _amp_#x02013 or Nox1 _amp_#x02013;/_amp_#x02013; _amp_#x02013 _amp_#x02013 females 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43758 17853944 55255 20202 10964 SLC22A18 HET HET 1 0.6 Nox -HET females were used for the next round of breeding against 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43759 17853944 55255 20996 11179 SOD1 SOD1 SOD1 12 3.9 females were used for the next round of breeding against SOD1 G93A hemizygous Nox -KO males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43760 17853944 55255 5281 2578 CYBB NOX2 Nox2 19 7.1 breeding against SOD1 G93A hemizygous Nox -KO males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 _amp_#x02013;/Y _amp_#x02013 Y 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43761 17853944 55255 20996 11179 SOD1 SOD1 SOD1 22 3.9 hemizygous Nox -KO males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 _amp_#x02013;/Y _amp_#x02013 Y or Nox1 +/_amp_#x02013; _amp_#x02013 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43762 17853944 55255 5281 2578 CYBB NOX2 Nox2 25 7.1 males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 _amp_#x02013;/Y _amp_#x02013 Y or Nox1 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43763 17853944 55255 14551 7889 NOX1 NOX1 Nox1 28 4.2 _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 _amp_#x02013;/Y _amp_#x02013 Y or Nox1 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox1 _amp_#x02013;/Y _amp_#x02013 Y 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43764 17853944 55255 20996 11179 SOD1 SOD1 SOD1 31 3.9 / Nox2 _amp_#x02013;/Y _amp_#x02013 Y or Nox1 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox1 _amp_#x02013;/Y _amp_#x02013 Y to give rise to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43765 17853944 55255 14551 7889 NOX1 NOX1 Nox1 34 4.2 _amp_#x02013 Y or Nox1 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox1 _amp_#x02013;/Y _amp_#x02013 Y to give rise to mixed litters containing 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43766 17853944 55255 20202 10964 SLC22A18 HET HET 50 0.6 mixed litters containing Nox -KO (male male and female Nox -HET (female female only and Nox -WT (male male only genotypes 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43767 17853944 55255 20996 11179 SOD1 SOD1 SOD1 65 3.9 (male male only genotypes either lacking or hemizygous for the SOD1 G93A transgene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43768 17853944 55256 20202 10964 SLC22A18 HET HET 2 0.6 Similarly Nox -HET females were also bred against SOD1 G93A hemizygous Nox -WT 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43769 17853944 55256 20996 11179 SOD1 SOD1 SOD1 8 3.9 Similarly Nox -HET females were also bred against SOD1 G93A hemizygous Nox -WT males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43770 17853944 55256 5281 2578 CYBB NOX2 Nox2 15 7.1 bred against SOD1 G93A hemizygous Nox -WT males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 +/Y Y or 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43771 17853944 55256 20996 11179 SOD1 SOD1 SOD1 18 3.9 hemizygous Nox -WT males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 +/Y Y or Nox1 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43772 17853944 55256 5281 2578 CYBB NOX2 Nox2 21 7.1 males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 +/Y Y or Nox1 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43773 17853944 55256 14551 7889 NOX1 NOX1 Nox1 24 4.2 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 +/Y Y or Nox1 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox1 +/Y Y to 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43774 17853944 55256 20996 11179 SOD1 SOD1 SOD1 27 3.9 G93A / Nox2 +/Y Y or Nox1 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox1 +/Y Y to give rise to mixed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43775 17853944 55256 14551 7889 NOX1 NOX1 Nox1 30 4.2 +/Y Y or Nox1 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox1 +/Y Y to give rise to mixed litters containing Nox 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43776 17853944 55256 20202 10964 SLC22A18 HET HET 45 0.6 to mixed litters containing Nox -KO (male male only Nox -HET (female female only and Nox -WT (male male and female 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43777 17853944 55256 20996 11179 SOD1 SOD1 SOD1 61 3.9 male and female genotypes either lacking or hemizygous for the SOD1 G93A transgene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43778 17853944 55257 5281 2578 CYBB NOX2 Nox2 2 7.1 Genotyping for Nox2 and SOD1 G93A mice was performed by standard PCR protocols 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43779 17853944 55257 20996 11179 SOD1 SOD1 SOD1 4 3.9 Genotyping for Nox2 and SOD1 G93A mice was performed by standard PCR protocols using primer 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43780 17853944 55258 14551 7889 NOX1 NOX1 Nox1 0 4.2 Nox1 PCR genotypes were performed as previously described ( 24 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43781 17853944 55260 20996 11179 SOD1 SOD1 SOD1 6 3.9 Methods Real-time quantitative PCR determination of SOD1 G93A transgene copy number 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43782 17853944 55261 20996 11179 SOD1 SOD1 hSOD1 23 2.2 in threshold cycle (_amp_#x00394;CT) _amp_#x00394 CT between the transgene ( hSOD1 and a reference gene ( mIL2 following a previously published 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43783 17853944 55261 10452 6001 IL2 IL2 mIL2 30 1.1 between the transgene ( hSOD1 and a reference gene ( mIL2 following a previously published protocol ( 25 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43784 17853944 55262 20996 11179 SOD1 SOD1 hSOD1 8 2.2 The following primers were used for the transgene hSOD1 forward 5_amp_#x02032 -CATCAGCCCTAATCCATCTGA-3_amp_#x02032 reverse 5_amp_#x02032 -CGCGACTAACAATCAAAGTGA-3_amp_#x02032 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43785 17853944 55263 10452 6001 IL2 IL2 mIL2 9 1.1 The following primers were used for the reference gene mIL2 forward 5_amp_#x02032 -CTAGGCCACAGAATTGAAAGATCT-3_amp_#x02032 reverse 5_amp_#x02032 -GTAGGTGGAAATTCTAGCATCATCC-3_amp_#x02032 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43786 17853944 55264 20996 11179 SOD1 SOD1 hSOD1 7 2.2 The final concentration of the primers for hSOD1 and mIL2 were 0.4 and 0.5 _amp_#x003bc M respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43787 17853944 55264 10452 6001 IL2 IL2 mIL2 9 1.1 The final concentration of the primers for hSOD1 and mIL2 were 0.4 and 0.5 _amp_#x003bc M respectively 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43788 17853944 55269 20996 11179 SOD1 SOD1 SOD1 10 3.9 _amp_#x00394 CT was calculated as the difference between the human SOD1 CT and the mouse IL2 CT for all mice in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43789 17853944 55269 5281 2578 CYBB NOX2 Nox2 22 7.1 and the mouse IL2 CT for all mice in the Nox2 F2 generation 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43790 17853944 55269 10452 6001 IL2 IL2 IL2 15 0.0 the difference between the human SOD1 CT and the mouse IL2 CT for all mice in the Nox2 F2 generation 10 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43791 17853944 55270 20996 11179 SOD1 SOD1 SOD1 30 3.9 24 and _amp_#x00394 CT (6.967) 6.967 of the B6SJL-TgN( B6SJL-TgN SOD1 G93A 1Gur as known values ( 26 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43792 17853944 55273 20996 11179 SOD1 SOD1 SOD1 1 3.9 B6SJL-Tg( B6SJL-Tg SOD1 G93A )1Gur/J 1Gur J mice hemizygous for a highly expressed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43793 17853944 55273 20996 11179 SOD1 SOD1 SOD1 11 3.9 )1Gur/J 1Gur J mice hemizygous for a highly expressed mutant SOD1 G93A transgene develop disease onset at approximately 110 days of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43794 17853944 55274 20996 11179 SOD1 SOD1 SOD1 10 3.9 our hands 50% survival was 123 days for B6SJL-Tg( B6SJL-Tg SOD1 G93A )1Gur/J 1Gur J males ( n = 30 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43795 17853944 55276 5281 2578 CYBB NOX2 Nox2 15 7.1 the study because their presymptomatic weight exceeded 40 g 2 Nox2 -WT 1 Nox2 -HET and 1 Nox2 -KO 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43796 17853944 55276 5281 2578 CYBB NOX2 Nox2 18 7.1 their presymptomatic weight exceeded 40 g 2 Nox2 -WT 1 Nox2 -HET and 1 Nox2 -KO 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43797 17853944 55276 20202 10964 SLC22A18 HET HET 19 0.6 presymptomatic weight exceeded 40 g 2 Nox2 -WT 1 Nox2 -HET and 1 Nox2 -KO 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43798 17853944 55276 5281 2578 CYBB NOX2 Nox2 22 7.1 40 g 2 Nox2 -WT 1 Nox2 -HET and 1 Nox2 -KO 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43799 17853944 55277 14551 7889 NOX1 NOX1 Nox1 6 4.2 None of the mice on the Nox1 -KO background failed the weight criteria 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43800 17853944 55281 5281 2578 CYBB NOX2 Nox2 0 7.1 Nox2 -KO mice also hemizygous for the SOD1 G93A transgene were 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43801 17853944 55281 20996 11179 SOD1 SOD1 SOD1 7 3.9 Nox2 -KO mice also hemizygous for the SOD1 G93A transgene were susceptible to superficial eye infections 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43802 17853944 55284 20996 11179 SOD1 SOD1 SOD1 12 3.9 that antibiotic treatment did not alter the course of disease SOD1 G93A / Nox2 -WT mice were put on antibiotic water 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43803 17853944 55284 5281 2578 CYBB NOX2 Nox2 15 7.1 did not alter the course of disease SOD1 G93A / Nox2 -WT mice were put on antibiotic water at 90 days 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43804 17853944 55285 5281 2578 CYBB NOX2 Nox2 3 7.1 Eye infection in Nox2 -HET females hemizygous for the SOD1 G93A transgene was only 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43805 17853944 55285 20202 10964 SLC22A18 HET HET 4 0.6 Eye infection in Nox2 -HET females hemizygous for the SOD1 G93A transgene was only observed 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43806 17853944 55285 20996 11179 SOD1 SOD1 SOD1 9 3.9 Eye infection in Nox2 -HET females hemizygous for the SOD1 G93A transgene was only observed in 1 of the 8 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43807 17853944 55285 5281 2578 CYBB NOX2 Nox2 27 7.1 of the 8 females analyzed and was never observed in Nox2 -KO mice lacking the SOD1 G93A transgene 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43808 17853944 55285 20996 11179 SOD1 SOD1 SOD1 32 3.9 and was never observed in Nox2 -KO mice lacking the SOD1 G93A transgene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43809 17853944 55312 15877 8512 OTC OTC OTC 4 0.0 Segments were embedded in OTC freezing medium and sectioned axially at 20 _amp_#x003bc m at 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43810 17853944 55319 10731 6149 ITGAM CD11b CD11b 6 1.0 Activated microglia were immunostained using a CD11b antibody from AbD Serotec Inc at a 1 100 dilution 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43811 17853944 55322 20996 11179 SOD1 SOD1 SOD1 15 3.9 spinal cord lysates made from the lumbar region of 120-day-old SOD1 G93A Nox2 -WT SOD1 G93A Nox2 -KO and nontransgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43812 17853944 55322 5281 2578 CYBB NOX2 Nox2 17 7.1 lysates made from the lumbar region of 120-day-old SOD1 G93A Nox2 -WT SOD1 G93A Nox2 -KO and nontransgenic mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43813 17853944 55322 20996 11179 SOD1 SOD1 SOD1 19 3.9 from the lumbar region of 120-day-old SOD1 G93A Nox2 -WT SOD1 G93A Nox2 -KO and nontransgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43814 17853944 55322 5281 2578 CYBB NOX2 Nox2 21 7.1 lumbar region of 120-day-old SOD1 G93A Nox2 -WT SOD1 G93A Nox2 -KO and nontransgenic mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43815 17853944 55331 14551 7889 NOX1 NOX1 Nox1 6 4.2 Results and Discussion Gene deletion of Nox1 or Nox2 increases survival and slows disease progression in SOD1 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43816 17853944 55331 5281 2578 CYBB NOX2 Nox2 8 7.1 Results and Discussion Gene deletion of Nox1 or Nox2 increases survival and slows disease progression in SOD1 G93A transgenic 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43817 17853944 55331 20996 11179 SOD1 SOD1 SOD1 16 3.9 Nox1 or Nox2 increases survival and slows disease progression in SOD1 G93A transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43818 17853944 55332 20996 11179 SOD1 ALS ALS 12 2.2 enhanced redox stress has been associated with disease progression in ALS mouse models we sought to evaluate 2 potential Nox genes 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43819 17853944 55332 18723 10261 ROS1 ROS ROS 25 0.3 we sought to evaluate 2 potential Nox genes responsible for ROS generation in hemizygous SOD1 G93A transgenic mice and their affect 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 43820 17853944 55332 20996 11179 SOD1 SOD1 SOD1 29 3.9 2 potential Nox genes responsible for ROS generation in hemizygous SOD1 G93A transgenic mice and their affect on the progression of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43821 17853944 55333 14551 7889 NOX1 NOX1 Nox1 3 4.2 We bred female Nox1 -KO and Nox2 -KO mice to hemizygous male SOD1 G93A 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43822 17853944 55333 5281 2578 CYBB NOX2 Nox2 6 7.1 We bred female Nox1 -KO and Nox2 -KO mice to hemizygous male SOD1 G93A ALS mice (Supplemental 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43823 17853944 55333 20996 11179 SOD1 SOD1 SOD1 12 3.9 female Nox1 -KO and Nox2 -KO mice to hemizygous male SOD1 G93A ALS mice (Supplemental Supplemental Figures 1 and 2 supplemental 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43824 17853944 55333 20996 11179 SOD1 ALS ALS 14 2.2 -KO and Nox2 -KO mice to hemizygous male SOD1 G93A ALS mice (Supplemental Supplemental Figures 1 and 2 supplemental material available 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43825 17853944 55334 14551 7889 NOX1 NOX1 Nox1 17 4.2 possible genotypes in both male and female siblings because both Nox1 and Nox2 are on the X chromosome 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43826 17853944 55334 5281 2578 CYBB NOX2 NOX2 17 7.1 possible genotypes in both male and female siblings because both Nox1 and Nox2 are on the X chromosome 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43827 17853944 55334 5281 2578 CYBB NOX2 Nox2 19 7.1 in both male and female siblings because both Nox1 and Nox2 are on the X chromosome 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43828 17853944 55335 20996 11179 SOD1 SOD1 SOD1 1 3.9 Mutant SOD1 transgene copy number was also stable throughout the F2 generations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43829 17853944 55336 14551 7889 NOX1 NOX1 Nox1 1 4.2 The Nox1 and Nox2 mice were both maintained on the C57BL/6 C57BL 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43830 17853944 55336 5281 2578 CYBB NOX2 NOX2 1 7.1 The Nox1 and Nox2 mice were both maintained on the C57BL/6 C57BL 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43831 17853944 55336 5281 2578 CYBB NOX2 Nox2 3 7.1 The Nox1 and Nox2 mice were both maintained on the C57BL/6 C57BL 6 background 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43832 17853944 55336 5281 2578 CYBB NOX2 Nox2 15 7.1 maintained on the C57BL/6 C57BL 6 background however only the Nox2 mice were inbred to greater than 13 generations ( Nox1 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43833 17853944 55336 14551 7889 NOX1 NOX1 Nox1 25 4.2 Nox2 mice were inbred to greater than 13 generations ( Nox1 KO mice were backcrossed about 7 generations onto the C57BL/6 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43834 17853944 55337 5281 2578 CYBB NOX2 Nox2 8 7.1 Unlike a previous study evaluating deletion of the Nox2 gene in SOD1 G93A C57BL/6J C57BL 6J inbred transgenic mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43835 17853944 55337 20996 11179 SOD1 SOD1 SOD1 11 3.9 a previous study evaluating deletion of the Nox2 gene in SOD1 G93A C57BL/6J C57BL 6J inbred transgenic mice ( 8 our 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43836 17853944 55337 20996 11179 SOD1 SOD1 SOD1 23 3.9 C57BL 6J inbred transgenic mice ( 8 our study used SOD1 G93A B6SJL mice on a mixed hybrid background (F1 F1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43837 17853944 55338 14551 7889 NOX1 NOX1 Nox1 4 4.2 Homozygous deletion of either Nox1 or Nox2 significantly delayed the death of hemizygous SOD1 G93A 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43838 17853944 55338 5281 2578 CYBB NOX2 Nox2 6 7.1 Homozygous deletion of either Nox1 or Nox2 significantly delayed the death of hemizygous SOD1 G93A ALS mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43839 17853944 55338 20996 11179 SOD1 SOD1 SOD1 13 3.9 either Nox1 or Nox2 significantly delayed the death of hemizygous SOD1 G93A ALS mice (Figure Figure 1 A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43840 17853944 55338 20996 11179 SOD1 ALS ALS 15 2.2 or Nox2 significantly delayed the death of hemizygous SOD1 G93A ALS mice (Figure Figure 1 A 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43841 17853944 55339 5281 2578 CYBB NOX2 Nox2 0 7.1 Nox2 gene deletion had the greatest impact on survival in both 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43842 17853944 55339 5281 2578 CYBB NOX2 Nox2 16 7.1 impact on survival in both male and female mice ( Nox2 -WT 132 days Nox2 -KO 229 days and also led 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43843 17853944 55339 5281 2578 CYBB NOX2 Nox2 20 7.1 both male and female mice ( Nox2 -WT 132 days Nox2 -KO 229 days and also led to a 4-fold increase 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43844 17853944 55340 5281 2578 CYBB NOX2 Nox2 8 7.1 The finding of an increased survival index in Nox2 -KO SOD1 G93A transgenic mice is significant because to our 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43845 17853944 55340 20996 11179 SOD1 SOD1 SOD1 10 3.9 The finding of an increased survival index in Nox2 -KO SOD1 G93A transgenic mice is significant because to our knowledge no 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43846 17853944 55341 14551 7889 NOX1 NOX1 Nox1-deficient 0 1.9 Nox1-deficient mice gave rise to a much smaller but still significant 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43847 17853944 55341 14551 7889 NOX1 NOX1 Nox1 18 4.2 but still significant protective effect in terms of survival ( Nox1 -WT 129 days Nox1 -KO 162 days but not survival 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43848 17853944 55341 14551 7889 NOX1 NOX1 Nox1 22 4.2 effect in terms of survival ( Nox1 -WT 129 days Nox1 -KO 162 days but not survival index (Figure Figure 1 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43849 17853944 55343 5281 2578 CYBB NOX2 Nox2 8 7.1 Given the significant 97-day increase in survival of Nox2 -KO SOD1 G93A B6SJL mice in our study compared with 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43850 17853944 55343 20996 11179 SOD1 SOD1 SOD1 10 3.9 Given the significant 97-day increase in survival of Nox2 -KO SOD1 G93A B6SJL mice in our study compared with the 13-day 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43851 17853944 55343 5281 2578 CYBB NOX2 Nox2 28 7.1 with the 13-day increase observed in a previous study using Nox2 -KO SOD1 G93A congenic C57BL/6J C57BL 6J mice ( 8 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43852 17853944 55343 20996 11179 SOD1 SOD1 SOD1 30 3.9 13-day increase observed in a previous study using Nox2 -KO SOD1 G93A congenic C57BL/6J C57BL 6J mice ( 8 we investigated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43853 17853944 55343 5281 2578 CYBB NOX2 Nox2 41 7.1 congenic C57BL/6J C57BL 6J mice ( 8 we investigated the Nox2 dependence of several disease-associated phenotypes at the cellular level 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43854 17853944 55344 20996 11179 SOD1 ALS ALS 3 2.2 Enhanced survival of ALS Nox2 -KO mice correlated with higher motor neuron counts in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43855 17853944 55344 5281 2578 CYBB NOX2 Nox2 4 7.1 Enhanced survival of ALS Nox2 -KO mice correlated with higher motor neuron counts in the 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43856 17853944 55344 10731 6149 ITGAM CD11b CD11b 32 1.0 120 days and reduced expression of the activated microglial marker CD11b (Figure Figure 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43857 17853944 55345 5281 2578 CYBB NOX2 Nox2 2 7.1 Deletion of Nox2 also resulted in reduced redox stress in spinal cords of 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43858 17853944 55346 5281 2578 CYBB NOX2 Nox2 10 7.1 These findings were similar to those observed in the previous Nox2 -KO SOD1 G93A congenic C57BL/6J C57BL 6J study ( 8 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43859 17853944 55346 20996 11179 SOD1 SOD1 SOD1 12 3.9 were similar to those observed in the previous Nox2 -KO SOD1 G93A congenic C57BL/6J C57BL 6J study ( 8 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43860 17853944 55347 5281 2578 CYBB NOX2 Nox2 26 7.1 death (Figure Figure 1 D were both significantly reduced in Nox2 -KO SOD1 G93A mice compared with Nox2 -WT SOD1 G93A 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43861 17853944 55347 20996 11179 SOD1 SOD1 SOD1 28 3.9 Figure 1 D were both significantly reduced in Nox2 -KO SOD1 G93A mice compared with Nox2 -WT SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43862 17853944 55347 5281 2578 CYBB NOX2 Nox2 33 7.1 significantly reduced in Nox2 -KO SOD1 G93A mice compared with Nox2 -WT SOD1 G93A mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43863 17853944 55347 20996 11179 SOD1 SOD1 SOD1 35 3.9 in Nox2 -KO SOD1 G93A mice compared with Nox2 -WT SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43864 17853944 55349 5281 2578 CYBB NOX2 Nox2 19 7.1 finding of decreased motor neuron disease in male and female Nox2 -KO ALS mice (Figure Figure 3 B_amp_#x02013 D 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43865 17853944 55349 20996 11179 SOD1 ALS ALS 21 2.2 decreased motor neuron disease in male and female Nox2 -KO ALS mice (Figure Figure 3 B_amp_#x02013 D 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43866 17853944 55350 20996 11179 SOD1 ALS ALS 20 2.2 by hind-limb muscle atrophy a hallmark of disease progression in ALS mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43867 17853944 55351 5281 2578 CYBB NOX2 Nox2 3 7.1 To determine whether Nox2 deficiency protected SOD1 G93A mice from muscle atrophy the weight 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43868 17853944 55351 20996 11179 SOD1 SOD1 SOD1 6 3.9 To determine whether Nox2 deficiency protected SOD1 G93A mice from muscle atrophy the weight fiber area and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43869 17853944 55352 5281 2578 CYBB NOX2 Nox2 3 7.1 At 100 days Nox2 -KO SOD1 G93A mice demonstrated significant protection from loss in 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43870 17853944 55352 20996 11179 SOD1 SOD1 SOD1 5 3.9 At 100 days Nox2 -KO SOD1 G93A mice demonstrated significant protection from loss in hind-limb muscle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43871 17853944 55352 5281 2578 CYBB NOX2 Nox2 19 7.1 significant protection from loss in hind-limb muscle mass compared with Nox2 -WT SOD1 G93A mice (Supplemental Supplemental Figure 5 A and 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43872 17853944 55352 20996 11179 SOD1 SOD1 SOD1 21 3.9 from loss in hind-limb muscle mass compared with Nox2 -WT SOD1 G93A mice (Supplemental Supplemental Figure 5 A and B 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43873 17853944 55353 5281 2578 CYBB NOX2 Nox2 7 7.1 These differences in muscle mass between the Nox2 genotypes of SOD1 G93A mice correlated with changes in muscle 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43874 17853944 55353 20996 11179 SOD1 SOD1 SOD1 10 3.9 These differences in muscle mass between the Nox2 genotypes of SOD1 G93A mice correlated with changes in muscle fiber area (Supplemental 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43875 17853944 55354 5281 2578 CYBB NOX2 Nox2 1 7.1 Furthermore Nox2 -KO SOD1 G93A mice were indistinguishable from nontransgenic littermates for 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43876 17853944 55354 20996 11179 SOD1 SOD1 SOD1 3 3.9 Furthermore Nox2 -KO SOD1 G93A mice were indistinguishable from nontransgenic littermates for both these 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43877 17853944 55356 20996 11179 SOD1 SOD1 SOD1 3 3.9 Breeding of hemizygous SOD1 G93A B6SJL mice onto the C57BL/6 C57BL 6 background has 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43878 17853944 55356 20996 11179 SOD1 SOD1 SOD1 25 3.9 to increase survival by approximately 13 to 14 days ( SOD1 G93A B6SJL hybrid mice 130.2 _amp_#x000b1 11.2 days SOD1 G93A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43879 17853944 55356 20996 11179 SOD1 SOD1 SOD1 34 3.9 ( SOD1 G93A B6SJL hybrid mice 130.2 _amp_#x000b1 11.2 days SOD1 G93A C57BL/6 C57BL 6 congenic mice 143.6 _amp_#x000b1 7.5 days 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43880 17853944 55357 20996 11179 SOD1 SOD1 SOD1 16 3.9 analysis demonstrated increases in survival averaging 28 days when comparing SOD1 G93A B6SJL hybrid mice (128.9 128.9 _amp_#x000b1 9.1 days with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43881 17853944 55357 20996 11179 SOD1 SOD1 SOD1 26 3.9 G93A B6SJL hybrid mice (128.9 128.9 _amp_#x000b1 9.1 days with SOD1 G93A C57BL/6J C57BL 6J congenic mice (157.1 157.1 _amp_#x000b1 9.3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43882 17853944 55358 20996 11179 SOD1 ALS ALS 14 2.2 C57BL/6 C57BL 6 modifier genes can slow disease progression in ALS mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43883 17853944 55359 20996 11179 SOD1 SOD1 SOD1 8 3.9 However the mean survival times for Nox -WT SOD1 G93A mice seen in our studies (129 129 and 132 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43884 17853944 55359 14551 7889 NOX1 NOX1 Nox1 20 4.2 seen in our studies (129 129 and 132 days for Nox1 and Nox2 backgrounds respectively were very similar to SOD1 G93A 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43885 17853944 55359 5281 2578 CYBB NOX2 NOX2 20 7.1 seen in our studies (129 129 and 132 days for Nox1 and Nox2 backgrounds respectively were very similar to SOD1 G93A 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43886 17853944 55359 5281 2578 CYBB NOX2 Nox2 22 7.1 our studies (129 129 and 132 days for Nox1 and Nox2 backgrounds respectively were very similar to SOD1 G93A B6SJL hybrid 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43887 17853944 55359 20996 11179 SOD1 SOD1 SOD1 29 3.9 for Nox1 and Nox2 backgrounds respectively were very similar to SOD1 G93A B6SJL hybrid mice in these previous reports 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43888 17853944 55360 5281 2578 CYBB NOX2 Nox2 7 7.1 Because a previous study using inbred C57BL/6 C57BL 6 Nox2 -KO SOD1 G93A mice demonstrated much smaller increases in survival 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43889 17853944 55360 20996 11179 SOD1 SOD1 SOD1 9 3.9 a previous study using inbred C57BL/6 C57BL 6 Nox2 -KO SOD1 G93A mice demonstrated much smaller increases in survival ( 8 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43890 17853944 55360 5281 2578 CYBB NOX2 Nox2 27 7.1 in survival ( 8 compared with our mixed B6SJL background Nox2 -KO SOD1 G93A mice we hypothesize that multiple SJL-derived modifier 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43891 17853944 55360 20996 11179 SOD1 SOD1 SOD1 29 3.9 ( 8 compared with our mixed B6SJL background Nox2 -KO SOD1 G93A mice we hypothesize that multiple SJL-derived modifier genes likely 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43892 17853944 55360 5281 2578 CYBB NOX2 Nox2 44 7.1 that multiple SJL-derived modifier genes likely act in concert with Nox2 deficiency to significantly enhance survival of SOD1 G93A mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43893 17853944 55360 20996 11179 SOD1 SOD1 SOD1 51 3.9 in concert with Nox2 deficiency to significantly enhance survival of SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43894 17853944 55361 14551 7889 NOX1 NOX1 Nox1 21 4.2 degree of variability in survival among siblings for the various Nox1 and Nox2 SOD1 G93A genotypes in the F1 and F2 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43895 17853944 55361 5281 2578 CYBB NOX2 NOX2 21 7.1 degree of variability in survival among siblings for the various Nox1 and Nox2 SOD1 G93A genotypes in the F1 and F2 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43896 17853944 55361 5281 2578 CYBB NOX2 Nox2 23 7.1 variability in survival among siblings for the various Nox1 and Nox2 SOD1 G93A genotypes in the F1 and F2 generations (Supplemental 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43897 17853944 55361 20996 11179 SOD1 SOD1 SOD1 24 3.9 in survival among siblings for the various Nox1 and Nox2 SOD1 G93A genotypes in the F1 and F2 generations (Supplemental Supplemental 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43898 17853944 55362 5281 2578 CYBB NOX2 Nox2 9 7.1 An embryonic stem cell_amp_#x02013 derived 129 segment linked to the Nox2 gene deletion near the telomere of the X chromosome likely 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43899 17853944 55362 5281 2578 CYBB NOX2 Nox2 23 7.1 the telomere of the X chromosome likely segregates with the Nox2 mutant allele 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43900 17853944 55363 5281 2578 CYBB NOX2 Nox2 21 7.1 to account for the increased survival seen in the B6SJL Nox2 -KO SOD1 G93A mice for 2 reasons 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43901 17853944 55363 20996 11179 SOD1 SOD1 SOD1 23 3.9 for the increased survival seen in the B6SJL Nox2 -KO SOD1 G93A mice for 2 reasons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43902 17853944 55364 20996 11179 SOD1 SOD1 SOD1 10 3.9 First studies that have evaluated 129 modifier genes on the SOD1 G86R C57BL/6 C57BL 6 background suggest that they do not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43903 17853944 55365 5281 2578 CYBB NOX2 Nox2 8 7.1 Second this 129-derived segment linked to the targeted Nox2 allele on the telomere of the X chromosome would certainly 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43904 17853944 55365 5281 2578 CYBB NOX2 Nox2 30 7.1 in the previous study that used inbred C57BL/6 C57BL 6 Nox2 -KO SOD1 G93A mice ( 8 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43905 17853944 55365 20996 11179 SOD1 SOD1 SOD1 32 3.9 previous study that used inbred C57BL/6 C57BL 6 Nox2 -KO SOD1 G93A mice ( 8 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43906 17853944 55366 5281 2578 CYBB NOX2 Nox2 7 7.1 Because we used the same inbred C57BL/6 C57BL 6 Nox2 -KO mice for breeding yet observed widely divergent survival rates 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43907 17853944 55366 5281 2578 CYBB NOX2 Nox2 19 7.1 mice for breeding yet observed widely divergent survival rates of Nox2 -KO SOD1 G93A mice it is unlikely this 129-linked segment 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43908 17853944 55366 20996 11179 SOD1 SOD1 SOD1 21 3.9 breeding yet observed widely divergent survival rates of Nox2 -KO SOD1 G93A mice it is unlikely this 129-linked segment can solely 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43909 17853944 55367 20996 11179 SOD1 SOD1 SOD1 4 3.9 Results and Discussion Female SOD1 G93A transgenic mice heterozygous for X-linked Nox genes have increased 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43910 17853944 55368 5281 2578 CYBB NOX2 Nox2 1 7.1 Interestingly Nox2 -HET female ALS mice also demonstrated significant increases in survival 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43911 17853944 55368 20202 10964 SLC22A18 HET HET 2 0.6 Interestingly Nox2 -HET female ALS mice also demonstrated significant increases in survival ( 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43912 17853944 55368 20996 11179 SOD1 ALS ALS 4 2.2 Interestingly Nox2 -HET female ALS mice also demonstrated significant increases in survival ( Nox2 -WT 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43913 17853944 55368 5281 2578 CYBB NOX2 Nox2 13 7.1 female ALS mice also demonstrated significant increases in survival ( Nox2 -WT 132 days Nox2 -HET 186 days Figure 1 A 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43914 17853944 55368 5281 2578 CYBB NOX2 Nox2 17 7.1 demonstrated significant increases in survival ( Nox2 -WT 132 days Nox2 -HET 186 days Figure 1 A and Figure 3 A 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43915 17853944 55368 20202 10964 SLC22A18 HET HET 18 0.6 significant increases in survival ( Nox2 -WT 132 days Nox2 -HET 186 days Figure 1 A and Figure 3 A although 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43916 17853944 55369 14551 7889 NOX1 NOX1 Nox1 13 4.2 a limited but significant heterozygous effect on increased survival in Nox1 -HET female ALS mice (Figure Figure 1 A 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43917 17853944 55369 20202 10964 SLC22A18 HET HET 14 0.6 limited but significant heterozygous effect on increased survival in Nox1 -HET female ALS mice (Figure Figure 1 A 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43918 17853944 55369 20996 11179 SOD1 ALS ALS 16 2.2 significant heterozygous effect on increased survival in Nox1 -HET female ALS mice (Figure Figure 1 A 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43919 17853944 55370 5281 2578 CYBB NOX2 Nox2 20 7.1 substantiated the finding of decreased motor neuron disease in female Nox2 -HET ALS mice (Figure Figure 3 B_amp_#x02013 D 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43920 17853944 55370 20202 10964 SLC22A18 HET HET 21 0.6 the finding of decreased motor neuron disease in female Nox2 -HET ALS mice (Figure Figure 3 B_amp_#x02013 D 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43921 17853944 55370 20996 11179 SOD1 ALS ALS 22 2.2 finding of decreased motor neuron disease in female Nox2 -HET ALS mice (Figure Figure 3 B_amp_#x02013 D 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43922 17853944 55371 14551 7889 NOX1 NOX1 Nox1 1 4.2 Both Nox1 and Nox2 genes reside on the X chromosome 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43923 17853944 55371 5281 2578 CYBB NOX2 NOX2 1 7.1 Both Nox1 and Nox2 genes reside on the X chromosome 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43924 17853944 55371 5281 2578 CYBB NOX2 Nox2 3 7.1 Both Nox1 and Nox2 genes reside on the X chromosome 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43925 17853944 55374 5281 2578 CYBB NOX2 Nox2 19 7.1 in female patients with X-linked chronic granulomatous disease caused by Nox2 gene mutations ( 17 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43926 17853944 55375 5281 2578 CYBB NOX2 Nox2 7 7.1 Given the significant protective effect seen in Nox2 -HET female mice we sought to determine how dosage of 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43927 17853944 55375 20202 10964 SLC22A18 HET HET 8 0.6 Given the significant protective effect seen in Nox2 -HET female mice we sought to determine how dosage of Nox2 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43928 17853944 55375 5281 2578 CYBB NOX2 Nox2 18 7.1 -HET female mice we sought to determine how dosage of Nox2 activity in the spinal cord might influence disease progression in 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43929 17853944 55375 20996 11179 SOD1 ALS ALS 29 2.2 activity in the spinal cord might influence disease progression in ALS mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43930 17853944 55376 5281 2578 CYBB NOX2 Nox2 13 7.1 end-stage disease Nox activity in the spinal cords of female Nox2 -HET SOD1 G93A mice fell between that of female Nox2 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43931 17853944 55376 20202 10964 SLC22A18 HET HET 14 0.6 disease Nox activity in the spinal cords of female Nox2 -HET SOD1 G93A mice fell between that of female Nox2 -KO 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43932 17853944 55376 20996 11179 SOD1 SOD1 SOD1 15 3.9 Nox activity in the spinal cords of female Nox2 -HET SOD1 G93A mice fell between that of female Nox2 -KO and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43933 17853944 55376 5281 2578 CYBB NOX2 Nox2 23 7.1 Nox2 -HET SOD1 G93A mice fell between that of female Nox2 -KO and Nox2 -WT SOD1 G93A mice (Figure Figure 1 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43934 17853944 55376 5281 2578 CYBB NOX2 Nox2 26 7.1 G93A mice fell between that of female Nox2 -KO and Nox2 -WT SOD1 G93A mice (Figure Figure 1 C 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43935 17853944 55376 20996 11179 SOD1 SOD1 SOD1 28 3.9 fell between that of female Nox2 -KO and Nox2 -WT SOD1 G93A mice (Figure Figure 1 C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43936 17853944 55377 5281 2578 CYBB NOX2 Nox2 9 7.1 This suggests that X-inactivation likely occurs randomly in female Nox2 -HET SOD1 G93A mice with about 50% of the microglia 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43937 17853944 55377 20202 10964 SLC22A18 HET HET 10 0.6 This suggests that X-inactivation likely occurs randomly in female Nox2 -HET SOD1 G93A mice with about 50% of the microglia and 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 43938 17853944 55377 20996 11179 SOD1 SOD1 SOD1 11 3.9 suggests that X-inactivation likely occurs randomly in female Nox2 -HET SOD1 G93A mice with about 50% of the microglia and neuronal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43939 17853944 55377 5281 2578 CYBB NOX2 Nox2 29 7.1 microglia and neuronal cell types predicted to be deficient for Nox2 function 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43940 17853944 55378 5281 2578 CYBB NOX2 Nox2 8 7.1 These findings demonstrate that a 50% reduction of Nox2 activity in the spinal cord has a significant impact on 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43941 17853944 55378 20996 11179 SOD1 ALS ALS 21 2.2 the spinal cord has a significant impact on survival of ALS mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43942 17853944 55379 5281 2578 CYBB NOX2 Nox2 7 7.1 It is presently unclear why chimerism for Nox2 expression in the spinal cord significantly influences survival but not 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43943 17853944 55379 20996 11179 SOD1 SOD1 SOD1 23 3.9 significantly influences survival but not the survival index in female SOD1 G93A transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43944 17853944 55380 20996 11179 SOD1 SOD1 SOD1 12 3.9 reports generating chimeric mice composed of mixtures of normal and SOD1 mutant_amp_#x02013 expressing non-neuronal cells significantly attenuated toxicity associated with mutant-expressing 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43945 17853944 55381 5281 2578 CYBB NOX2 Nox2 2 7.1 Given that Nox2 is highly expressed in microglia of SOD1 G93A transgenic mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43946 17853944 55381 20996 11179 SOD1 SOD1 SOD1 9 3.9 Given that Nox2 is highly expressed in microglia of SOD1 G93A transgenic mice ( 8 chimerism of Nox2 gene expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43947 17853944 55381 5281 2578 CYBB NOX2 Nox2 18 7.1 microglia of SOD1 G93A transgenic mice ( 8 chimerism of Nox2 gene expression in microglia appears to influence disease progression 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43948 17853944 55382 20996 11179 SOD1 ALS ALS 6 2.2 It has been postulated that the ALS phenotype is at least partially dictated by an altered redox-balance 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43949 17853944 55382 20996 11179 SOD1 SOD1 SOD1 22 3.9 dictated by an altered redox-balance within cells expressing the mutant SOD1 through an as-yet undefined gain of function ( 2 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43950 17853944 55383 20996 11179 SOD1 SOD1 SOD1 8 3.9 A recent study using conditional elimination of mutant SOD1 in neurons or glial cells has also demonstrated that these 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43951 17853944 55384 20996 11179 SOD1 ALS ALS 16 2.2 findings our current data demonstrating significantly enhanced survival in female ALS mice with chimeric Nox2 expression suggest that SOD1 G93A expression 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43952 17853944 55384 5281 2578 CYBB NOX2 Nox2 20 7.1 demonstrating significantly enhanced survival in female ALS mice with chimeric Nox2 expression suggest that SOD1 G93A expression in microglia may directly 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43953 17853944 55384 20996 11179 SOD1 SOD1 SOD1 24 3.9 in female ALS mice with chimeric Nox2 expression suggest that SOD1 G93A expression in microglia may directly influence deleterious cell-autonomous function 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43954 17853944 55384 5281 2578 CYBB NOX2 Nox2 36 7.1 expression in microglia may directly influence deleterious cell-autonomous function of Nox2 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43955 17853944 55385 5281 2578 CYBB NOX2 Nox2 3 7.1 Results and Discussion Nox2 deficiency leads to an enhanced predisposition to lethal eye infections 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43956 17853944 55385 20996 11179 SOD1 SOD1 SOD1 15 3.9 leads to an enhanced predisposition to lethal eye infections in SOD1 G93A transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43957 17853944 55386 5281 2578 CYBB NOX2 Nox2 3 7.1 Notably in the Nox2 -KO SOD1 G93A transgenic background we observed a high frequency 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43958 17853944 55386 20996 11179 SOD1 SOD1 SOD1 5 3.9 Notably in the Nox2 -KO SOD1 G93A transgenic background we observed a high frequency of eye 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43959 17853944 55388 5281 2578 CYBB NOX2 Nox2 6 7.1 These infections were never observed in Nox2 -KO littermates lacking the SOD1 G93A transgene 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43960 17853944 55388 20996 11179 SOD1 SOD1 SOD1 11 3.9 infections were never observed in Nox2 -KO littermates lacking the SOD1 G93A transgene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43961 17853944 55390 20996 11179 SOD1 ALS ALS 5 2.2 Importantly antibiotic treatment of control ALS mice on the WT Nox2 background did not alter either 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43962 17853944 55390 5281 2578 CYBB NOX2 Nox2 10 7.1 Importantly antibiotic treatment of control ALS mice on the WT Nox2 background did not alter either the progression of motor neuron 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43963 17853944 55392 5281 2578 CYBB NOX2 Nox2 13 7.1 was rapid accumulation of secretions around the eye from affected Nox2 -KO SOD1 G93A transgenic mice suffering from infections (Supplemental Supplemental 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43964 17853944 55392 20996 11179 SOD1 SOD1 SOD1 15 3.9 accumulation of secretions around the eye from affected Nox2 -KO SOD1 G93A transgenic mice suffering from infections (Supplemental Supplemental Figure 6A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43965 17853944 55393 5281 2578 CYBB NOX2 Nox2 17 7.1 glands (the the Harderian gland and lacrimal gland of affected Nox2 -KO SOD1 G93A transgenic mice compared with Nox2 -WT SOD1 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43966 17853944 55393 20996 11179 SOD1 SOD1 SOD1 19 3.9 the Harderian gland and lacrimal gland of affected Nox2 -KO SOD1 G93A transgenic mice compared with Nox2 -WT SOD1 G93A transgenic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43967 17853944 55393 5281 2578 CYBB NOX2 Nox2 25 7.1 of affected Nox2 -KO SOD1 G93A transgenic mice compared with Nox2 -WT SOD1 G93A transgenic mice ( n = 3 per 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43968 17853944 55393 20996 11179 SOD1 SOD1 SOD1 27 3.9 Nox2 -KO SOD1 G93A transgenic mice compared with Nox2 -WT SOD1 G93A transgenic mice ( n = 3 per group 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43969 17853944 55394 5281 2578 CYBB NOX2 Nox2 5 7.1 First the Harderian gland of Nox2 -WT SOD1 G93A transgenic mice always contained accumulated porphyrin aggregates 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43970 17853944 55394 20996 11179 SOD1 SOD1 SOD1 7 3.9 First the Harderian gland of Nox2 -WT SOD1 G93A transgenic mice always contained accumulated porphyrin aggregates in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43971 17853944 55394 5281 2578 CYBB NOX2 Nox2 28 7.1 lumen of glandular tubules that were never seen in affected Nox2 -KO SOD1 G93A transgenic mice (Supplemental Supplemental Figure 6 C 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43972 17853944 55394 20996 11179 SOD1 SOD1 SOD1 30 3.9 glandular tubules that were never seen in affected Nox2 -KO SOD1 G93A transgenic mice (Supplemental Supplemental Figure 6 C and F 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43973 17853944 55397 5281 2578 CYBB NOX2 Nox2 13 7.1 possible that altered secretions from the Harderian gland of affected Nox2 -KO SOD1 G93A transgenic mice influence the observed increased predisposition 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43974 17853944 55397 20996 11179 SOD1 SOD1 SOD1 15 3.9 altered secretions from the Harderian gland of affected Nox2 -KO SOD1 G93A transgenic mice influence the observed increased predisposition to bacterial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43975 17853944 55398 5281 2578 CYBB NOX2 Nox2 15 7.1 architecture of the lacrimal glands were also observed in affected Nox2 -KO SOD1 G93A transgenic mice (Supplemental Supplemental Figure 6 D 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43976 17853944 55398 20996 11179 SOD1 SOD1 SOD1 17 3.9 the lacrimal glands were also observed in affected Nox2 -KO SOD1 G93A transgenic mice (Supplemental Supplemental Figure 6 D and G 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43977 17853944 55400 5281 2578 CYBB NOX2 Nox2 22 7.1 may account for increased incidence of infection in eyes of Nox2 -KO SOD1 G93A transgenic mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43978 17853944 55400 20996 11179 SOD1 SOD1 SOD1 24 3.9 for increased incidence of infection in eyes of Nox2 -KO SOD1 G93A transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43979 17853944 55401 20996 11179 SOD1 SOD1 SOD1 7 3.9 It is presently unclear why overexpression of SOD1 G93A manifests these abnormalities only on the Nox2 -KO background 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43980 17853944 55401 5281 2578 CYBB NOX2 Nox2 15 7.1 overexpression of SOD1 G93A manifests these abnormalities only on the Nox2 -KO background 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43981 17853944 55402 20996 11179 SOD1 SOD1 SOD1 9 3.9 However the findings imply potential new functions for both SOD1 and Nox2 in eye innate immunity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43982 17853944 55402 5281 2578 CYBB NOX2 Nox2 11 7.1 the findings imply potential new functions for both SOD1 and Nox2 in eye innate immunity 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43983 17853944 55404 5281 2578 CYBB NOX2 Nox2 4 7.1 Compromised immune function in Nox2 -KO animals likely contributed to the lack of inflammation in 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43984 17853944 55407 20996 11179 SOD1 ALS ALS 13 2.2 cannot explain why the infection was only present in the ALS Nox2 -KO mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43985 17853944 55407 5281 2578 CYBB NOX2 Nox2 14 7.1 explain why the infection was only present in the ALS Nox2 -KO mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43986 17853944 55411 18723 10261 ROS1 ROS ROS 13 0.3 microglia can lead to the production of proinflammatory cytokines and ROS which have been associated with neuroinflammation that can further perpetuate 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 43987 17853944 55412 18723 10261 ROS1 ROS ROS 7 0.3 Among the factors produced by activated microglia ROS could potentially enhance neurodegeneration by at least 2 mechanisms 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 43988 17853944 55413 18723 10261 ROS1 ROS ROS 1 0.3 First ROS can cause direct damage to neurons 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 43989 17853944 55414 18723 10261 ROS1 ROS ROS 7 0.3 Second increases in the intracellular concentrations of ROS may activate pro-inflammatory signaling cascades that result in the activation 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 43990 17853944 55415 20996 11179 SOD1 ALS ALS 15 2.2 there is an upregulation of microglia during the progression of ALS disease and that in Nox2 -KO mice there is a 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43991 17853944 55415 5281 2578 CYBB NOX2 Nox2 20 7.1 microglia during the progression of ALS disease and that in Nox2 -KO mice there is a marked decrease in the number 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43992 17853944 55415 10676 6121 IRF6 LPS LPS 35 0.3 a marked decrease in the number of activated microglia following LPS treatment ( 21 1 JUMiner_v2.2 1 2 UserEdit 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 1 1 0 0 0 43993 17853944 55416 18723 10261 ROS1 ROS ROS 3 0.3 This suggests that ROS generated from NADPH oxidases play a role in signaling events 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 43994 17853944 55417 20996 11179 SOD1 ALS ALS 15 2.2 to determine the effect of NADPH oxidase_amp_#x02013 derived superoxide in ALS disease progression in transgenic mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 43995 17853944 55418 14551 7889 NOX1 NOX1 Nox1 13 4.2 survival and delayed disease onset when 2 related Nox genes Nox1 and Nox2 were deleted 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43996 17853944 55418 5281 2578 CYBB NOX2 NOX2 13 7.1 survival and delayed disease onset when 2 related Nox genes Nox1 and Nox2 were deleted 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43997 17853944 55418 5281 2578 CYBB NOX2 Nox2 15 7.1 delayed disease onset when 2 related Nox genes Nox1 and Nox2 were deleted 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43998 17853944 55420 20996 11179 SOD1 SOD1 SOD1 5 3.9 Interestingly our findings in female SOD1 G93A transgenic mice heterozygous for the Nox2 X-linked gene and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 43999 17853944 55420 5281 2578 CYBB NOX2 Nox2 12 7.1 findings in female SOD1 G93A transgenic mice heterozygous for the Nox2 X-linked gene and hence containing 50% Nox2-inactive cells suggest that 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44000 17853944 55420 5281 2578 CYBB NOX2 Nox2-inactive 19 2.0 heterozygous for the Nox2 X-linked gene and hence containing 50% Nox2-inactive cells suggest that the interplay between Nox-activated microglia and neuronal 15 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 44001 17853944 55420 20996 11179 SOD1 ALS ALS 33 2.2 the interplay between Nox-activated microglia and neuronal cell types in ALS may be more complex than previously thought 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44002 17853944 55421 5281 2578 CYBB NOX2 Nox2 21 7.1 failed to find substantial protection against motor neuron defects in Nox2 -KO SOD1 G93A transgenic mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44003 17853944 55421 20996 11179 SOD1 SOD1 SOD1 23 3.9 find substantial protection against motor neuron defects in Nox2 -KO SOD1 G93A transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44004 17853944 55424 20996 11179 SOD1 ALS ALS 11 2.2 genetic background has previously been shown to influence survival of ALS mice ( 13 and this could have accounted for the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44005 17853944 55425 14551 7889 NOX1 NOX1 Nox1 10 4.2 However the marginal increase in life span seen in the Nox1 -KO compared with the Nox2 -KO ALS mice would suggest 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44006 17853944 55425 5281 2578 CYBB NOX2 Nox2 15 7.1 life span seen in the Nox1 -KO compared with the Nox2 -KO ALS mice would suggest that modifier genes must act 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44007 17853944 55425 20996 11179 SOD1 ALS ALS 17 2.2 seen in the Nox1 -KO compared with the Nox2 -KO ALS mice would suggest that modifier genes must act in concert 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44008 17853944 55425 5281 2578 CYBB NOX2 Nox2 29 7.1 would suggest that modifier genes must act in concert with Nox2 deficiency to provide substantial improvements in survival 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44009 17853944 55426 5281 2578 CYBB NOX2 Nox2 10 7.1 The potential existence of additional modifier genes that may influence Nox2 function in ALS would be particularly relevant to human ALS 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44010 17853944 55426 20996 11179 SOD1 ALS ALS 13 2.2 of additional modifier genes that may influence Nox2 function in ALS would be particularly relevant to human ALS disease which manifests 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44011 17853944 55426 20996 11179 SOD1 ALS ALS 20 2.2 Nox2 function in ALS would be particularly relevant to human ALS disease which manifests considerable phenotypic variability 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44012 17853944 55428 20996 11179 SOD1 ALS ALS 9 2.2 First we believe the demonstrated increase in survival of ALS mice is the largest ever reported as a consequence of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44013 17853944 55428 5281 2578 CYBB NOX2 Nox2 25 7.1 reported as a consequence of disrupting a single gene ( Nox2 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44014 17853944 55429 14551 7889 NOX1 NOX1 Nox1 12 4.2 studies also demonstrate that more than 1 Nox gene ( Nox1 and Nox2 can influence disease progression in ALS mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44015 17853944 55429 5281 2578 CYBB NOX2 NOX2 12 7.1 studies also demonstrate that more than 1 Nox gene ( Nox1 and Nox2 can influence disease progression in ALS mice 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44016 17853944 55429 5281 2578 CYBB NOX2 Nox2 14 7.1 demonstrate that more than 1 Nox gene ( Nox1 and Nox2 can influence disease progression in ALS mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44017 17853944 55429 20996 11179 SOD1 ALS ALS 21 2.2 gene ( Nox1 and Nox2 can influence disease progression in ALS mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44018 17853944 55430 20996 11179 SOD1 ALS ALS 19 2.2 deletions have been shown to significantly delay disease progression in ALS mice (i.e., i.e. survival index 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44019 17853944 55431 20996 11179 SOD1 ALS ALS 5 2.2 Finally our findings in female ALS mice suggest that a 50% reduction in Nox2 activity can 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44020 17853944 55431 5281 2578 CYBB NOX2 Nox2 13 7.1 in female ALS mice suggest that a 50% reduction in Nox2 activity can significantly alter the progression of disease in this 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44021 17853944 55431 20996 11179 SOD1 SOD1 SOD1 24 3.9 activity can significantly alter the progression of disease in this SOD1 G93A transgenic model of ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44022 17853944 55431 20996 11179 SOD1 ALS ALS 29 2.2 progression of disease in this SOD1 G93A transgenic model of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44023 17853944 55432 20996 11179 SOD1 ALS ALS 17 2.2 Nox pathways using pharmacologic-based approaches could provide significant benefits for ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44024 17853944 55437 20996 11179 SOD1 ALS ALS 4 2.2 Footnotes Nonstandard abbreviations used ALS amyotrophic lateral sclerosis CT threshold cycle HET heterozygous SOD superoxide 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44025 17853944 55437 20202 10964 SLC22A18 HET HET 11 0.6 Nonstandard abbreviations used ALS amyotrophic lateral sclerosis CT threshold cycle HET heterozygous SOD superoxide dismutase 1 JUMiner_v2.2 1 2 UserEdit 0 2 10520 TotalCon:2<>10520|SAFB|6294|Complete__10964|SLC22A18|5002|Complete__<>AvaiableGeneRif=2<>BEST:10520|SAFB|0.000455539358600583<>ScoreDetail__10520|SAFB|0.000455539358600583__10964|SLC22A18|0.000385868633167553__ 1 1 0 0 0 44026 17853944 55437 20996 11179 SOD1 SOD SOD 13 2.2 used ALS amyotrophic lateral sclerosis CT threshold cycle HET heterozygous SOD superoxide dismutase 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44027 17853944 55441 14551 7889 NOX1 NOX1 Nox1 8 4.2 Figure 1 Deletion of NADPH oxidase genes ( Nox1 or Nox2 enhances survival and survival index in ALS mice 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44028 17853944 55441 5281 2578 CYBB NOX2 Nox2 10 7.1 Figure 1 Deletion of NADPH oxidase genes ( Nox1 or Nox2 enhances survival and survival index in ALS mice and significantly 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44029 17853944 55441 20996 11179 SOD1 ALS ALS 18 2.2 ( Nox1 or Nox2 enhances survival and survival index in ALS mice and significantly reduces superoxide production in spinal cords of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 44030 17853944 55441 20996 11179 SOD1 SOD1 SOD1 30 3.9 and significantly reduces superoxide production in spinal cords of end-stage SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44031 17853944 55442 5281 2578 CYBB NOX2 Nox2 2 7.1 Figure 2 Nox2 deficiency rescues motor neuron death in the spinal cords of 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44032 17853944 55442 20996 11179 SOD1 SOD1 SOD1 17 3.9 death in the spinal cords of mice hemizygous for the SOD1 G93A transgene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44033 17853944 55443 5281 2578 CYBB NOX2 Nox2 5 7.1 Figure 3 Disease phenotyping of Nox2 genotypes on the SOD1 G93A ALS background 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44034 17853944 55443 20996 11179 SOD1 SOD1 SOD1 9 3.9 Figure 3 Disease phenotyping of Nox2 genotypes on the SOD1 G93A ALS background 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 44035 17853944 55443 20996 11179 SOD1 ALS ALS 11 2.2 3 Disease phenotyping of Nox2 genotypes on the SOD1 G93A ALS background 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00177027188415898<>ScoreDetail__5468|IGFALS|0.0008079344737282__11179|SOD1|0.00177027188415898__ 0 0 0 0 0 45271 17896980 57305 14373 7808 NGF NGF NGF 3 1.2 Nerve growth factor (NGF) NGF and brain-derived neurotrophic factor (BDNF) BDNF belong to the protein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 45272 17896980 57305 1624 1033 BDNF BDNF BDNF 8 1.9 Nerve growth factor (NGF) NGF and brain-derived neurotrophic factor (BDNF) BDNF belong to the protein family of neurotrophins 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 45273 17896980 57307 14373 7808 NGF NGF NGF 1 1.2 Moreover NGF and BDNF are known to modulate immune cell function and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 45274 17896980 57307 1624 1033 BDNF BDNF BDNF 3 1.9 Moreover NGF and BDNF are known to modulate immune cell function and thus serve 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 45275 17896980 57308 9947 5468 IGFALS ALS ALS 23 0.3 and the immune system such as amyotrophic lateral sclerosis (ALS), ALS Alzheimer's disease (AD), AD neuropathy pain allergic bronchial asthma (BA) 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00061616799804828<>ScoreDetail__5468|IGFALS|0.000489585187822681__11179|SOD1|0.00061616799804828__ 0 0 0 0 0 45276 17896980 57310 14373 7808 NGF NGF NGF 15 1.2 an overview of the pathophysiology therapeutic interventions and strategies concerning NGF and BDNF in the mentioned diseases 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 45277 17896980 57310 1624 1033 BDNF BDNF BDNF 17 1.9 of the pathophysiology therapeutic interventions and strategies concerning NGF and BDNF in the mentioned diseases 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46107 17901552 58245 17610 9605 PTGS2 COX-2 COX-2 2 1.0 Function of COX-2 and prostaglandins in neurological disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46108 17901552 58246 17610 9605 PTGS2 COX-2 COX-2 2 1.0 Induction of COX-2 expression and enzymatic activity promotes neuronal injury in a number 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46109 17901552 58247 17610 9605 PTGS2 COX-2 COX-2 2 1.0 Inhibition of COX-2 activity either genetically or pharmacologically has been shown to be 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46110 17901552 58248 926 620 APP amyloid amyloid 12 1.0 activity with nonsteroidal anti-inflammatory drugs (NSAIDs) NSAIDs reduces inflammation and amyloid accumulation in murine transgenic models of Familial Alzheimer's disease and 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 46111 17901552 58248 17610 9605 PTGS2 COX COX 2 0.0 Inhibition of COX activity with nonsteroidal anti-inflammatory drugs (NSAIDs) NSAIDs reduces inflammation and 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 46112 17901552 58249 17595 9592 PTGDS PGD2 PGD2 18 1.3 downstream effects of one or more prostaglandin products including PGE2 PGD2 PGF2alpha PGI2 (prostacylin) prostacylin and TXA2 (thromboxane) thromboxane that effect 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46113 17901552 58249 17610 9605 PTGS2 COX COX-mediated 0 0.0 COX-mediated neuronal injury is presumed be due to downstream effects of 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 46114 17901552 58250 17610 9605 PTGS2 COX-2 COX-2 25 1.0 that are paradoxically protective when taken in the context that COX-2 induces neuronal injury in the setting of excitotoxicity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46115 17901552 58251 17597 9594 PTGER2 EP2 EP2 9 0.6 Conversely in the context of an inflammatory stimulus the EP2 receptor enhances neuronal injury 1 JUMiner_v2.2 1 0 0 2 9594 TotalCon:2<>9594|PTGER2|5732|Complete__14534|SPAG11B|10407|Complete__<>AvaiableGeneRif=2<>BEST:9594|PTGER2|0.00127542768417453<>ScoreDetail__9594|PTGER2|0.00127542768417453__14534|SPAG11B|0.000471648674143172__ 0 0 0 0 0 46158 17908040 58278 22551 11892 TNF TNF-alpha TNF-alpha 0 3.7 TNF-alpha inhibition as a treatment strategy for neurodegenerative disorders new drug 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46159 17908040 58283 22551 11892 TNF TNF-alpha TNF-alpha 23 3.7 the potent pro-inflammatory / pro-apoptotic cytokine tumor necrosis factor-alpha (TNF-alpha) TNF-alpha 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46160 17908040 58284 22551 11892 TNF TNF-alpha TNF-alpha 0 3.7 TNF-alpha is secreted by the brain resident marcophage (the the microglial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46161 17908040 58285 20996 11179 SOD1 ALS ALS 24 0.0 cell death in AD PD and amyotrophic lateral sclerosis (ALS) ALS as well as several other CNS complications 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000555587013653184<>ScoreDetail__5468|IGFALS|0.00026542800265428__11179|SOD1|0.000555587013653184__ 0 0 0 0 0 46162 17908040 58286 22551 11892 TNF TNF-alpha TNF-alpha 9 3.7 Recently agents that modulate the levels of circulating peripheral TNF-alpha protein have been shown to be worthwhile therapeutic agents with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46163 17908040 58288 22551 11892 TNF TNF-alpha TNF-alpha 8 3.7 However thalidomide a small molecule drug can inhibit TNF-alpha protein synthesis and unlike larger molecules is readily capable of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 46164 17908040 58290 22551 11892 TNF TNF-alpha TNF-alpha 10 3.7 Consequently we have chosen to discuss the relevance of unregulated TNF-alpha expression in illnesses of the CNS and to an extent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38593 17969353 48250 9947 5468 IGFALS ALS ALS 8 0.3 Gene expression profile of spinal ventral horn in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00103931458879183<>ScoreDetail__5468|IGFALS|0.00073946853680645__11179|SOD1|0.00103931458879183__ 0 0 0 0 0 38594 17969353 48251 9947 5468 IGFALS ALS ALS 8 0.3 The causative pathomechanism of sporadic amyotrophic lateral sclerosis (ALS) ALS is not clearly understood 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00103931458879183<>ScoreDetail__5468|IGFALS|0.00073946853680645__11179|SOD1|0.00103931458879183__ 0 0 0 0 0 38595 17969353 48252 9947 5468 IGFALS ALS ALS 26 0.3 well as spinal ventral horn from autopsied patients with sporadic ALS were examined 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00103931458879183<>ScoreDetail__5468|IGFALS|0.00073946853680645__11179|SOD1|0.00103931458879183__ 0 0 0 0 0 38596 17969353 48256 5514 2711 DCTN1 DCTN1 DCTN1 20 0.6 cell surface antigens/receptors, antigens receptors such as dynactin 1 (DCTN1) DCTN1 and early growth response 3 (EGR3) EGR3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38597 17969353 48256 6452 3240 EGR3 EGR3 EGR3 26 2.5 dynactin 1 (DCTN1) DCTN1 and early growth response 3 (EGR3) EGR3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38598 17969353 48257 5514 2711 DCTN1 DCTN1 DCTN1 2 0.6 In particular DCTN1 was markedly downregulated in most residual motor neurons prior to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38599 17969353 48258 3788 1578 CCNA2 CCNA CCNA 14 1.0 5 (DR5), DR5 cyclins C (CCNC) CCNC and A1 (CCNA), CCNA and caspases were upregulated whereas cell death inhibitors acetyl-CoA transporter 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38600 17969353 48258 20303 95 SLC33A1 ACATN ACATN 25 1.3 caspases were upregulated whereas cell death inhibitors acetyl-CoA transporter (ACATN) ACATN and NF-kappaB (NFKB) NFKB were also upregulated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38601 17969353 48258 14352 7794 NFKB1 NF-kappaB NF-kappaB 27 0.5 upregulated whereas cell death inhibitors acetyl-CoA transporter (ACATN) ACATN and NF-kappaB (NFKB) NFKB were also upregulated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38602 17969353 48258 14352 7794 NFKB1 NFKB NFKB 28 0.5 cell death inhibitors acetyl-CoA transporter (ACATN) ACATN and NF-kappaB (NFKB) NFKB were also upregulated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38603 17969353 48258 22568 11905 TNFRSF10B DR5 DR5 8 0.0 Promoters for cell death pathway death receptor 5 (DR5), DR5 cyclins C (CCNC) CCNC and A1 (CCNA), CCNA and caspases 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38604 17969353 48258 3793 1581 CCNC CCNC CCNC 11 0.0 death pathway death receptor 5 (DR5), DR5 cyclins C (CCNC) CCNC and A1 (CCNA), CCNA and caspases were upregulated whereas cell 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38605 17969353 48259 13346 7178 MMRN1 ECM ECM 18 0.0 cell surface antigens/receptors, antigens receptors transcription and cell adhesion/ECM adhesion ECM were increased 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38606 17969353 48262 5514 2711 DCTN1 DCTN1 DCTN1 10 0.6 The sequence of motor neuron-specific gene expression changes from early DCTN1 downregulation to late CCNC upregulation in sporadic ALS can provide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 38607 17969353 48262 9947 5468 IGFALS ALS ALS 18 0.3 from early DCTN1 downregulation to late CCNC upregulation in sporadic ALS can provide direct information on the genes leading to neurodegeneration 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00103931458879183<>ScoreDetail__5468|IGFALS|0.00073946853680645__11179|SOD1|0.00103931458879183__ 0 0 0 0 0 38608 17969353 48262 3793 1581 CCNC CCNC CCNC 14 0.0 neuron-specific gene expression changes from early DCTN1 downregulation to late CCNC upregulation in sporadic ALS can provide direct information on the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27677 17997855 32892 20996 11179 SOD1 ALS ALS 13 1.9 the course of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27678 17997855 32893 20996 11179 SOD1 SOD1 SOD1 10 3.2 the anti-oxidant enzyme Cu Zn superoxide dismutase (EC EC 1.15.1.1 SOD1 are associated with familial ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27679 17997855 32893 20996 11179 SOD1 ALS ALS 15 1.9 superoxide dismutase (EC EC 1.15.1.1 SOD1 are associated with familial ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27680 17997855 32895 20996 11179 SOD1 SOD1 SOD1 10 3.2 Methods SH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) G93A-SOD1 and SH-SY5Y neuroblastoma cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27681 17997855 32895 20996 11179 SOD1 ALS ALS 14 1.9 transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) G93A-SOD1 and SH-SY5Y neuroblastoma cells transfected with wildtype SOD1 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27682 17997855 32895 20996 11179 SOD1 SOD1 SOD1 23 3.2 ALS (G93A-SOD1) G93A-SOD1 and SH-SY5Y neuroblastoma cells transfected with wildtype SOD1 were both exposed to pneumolysin and in co-cultures with cultured 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27683 17997855 32895 5021 2444 CSK CSK CSK 50 0.0 S -lysyl- S -lysine _amp_#x000d7 3 HCl (Pam Pam 3 CSK 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27684 17997855 32899 20996 11179 SOD1 SOD1 SOD1 10 3.2 Results SH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) G93A-SOD1 were more vulnerable to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27685 17997855 32899 20996 11179 SOD1 ALS ALS 14 1.9 transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) G93A-SOD1 were more vulnerable to the neurotoxic action of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27686 17997855 32899 20996 11179 SOD1 SOD1 SOD1 44 3.2 3 CSK 4 than SH-SY5Y cells transfected with wild-type human SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27687 17997855 32899 5021 2444 CSK CSK CSK 35 0.0 and to the attack of monocytes stimulated by Pam 3 CSK 4 than SH-SY5Y cells transfected with wild-type human SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27688 17997855 32903 20996 11179 SOD1 ALS ALS 21 1.9 inflammation may be partly responsible for the clinical deterioration of ALS patients during infections 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27689 17997855 32904 20996 11179 SOD1 ALS ALS 16 1.9 neuron disease and suggest early treatment of respiratory infections in ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27690 17997855 32906 20996 11179 SOD1 ALS ALS 23 1.9 Alzheimer's disease Parkinson's disease stroke and amyotrophic lateral sclerosis (ALS) ALS 1 2 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27691 17997855 32908 20996 11179 SOD1 ALS ALS 8 1.9 In support of the link between infections and ALS an epidemiological study found evidence for infection with Mycoplasma spp 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27692 17997855 32908 20996 11179 SOD1 ALS ALS 30 1.9 the blood of more than 80% of patients suffering from ALS and in less than 10% of age-matched control subjects 3 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27693 17997855 32908 9401 16435 HM13 SPP spp 18 0.0 ALS an epidemiological study found evidence for infection with Mycoplasma spp in the blood of more than 80% of patients suffering 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27694 17997855 32909 20996 11179 SOD1 ALS ALS 0 1.9 ALS is an ultimately lethal disease with a high inter-subject variation 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27695 17997855 32911 20996 11179 SOD1 ALS ALS 0 1.9 ALS appears to be a multifactorial disease where motor neuron degradation 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27696 17997855 32912 20996 11179 SOD1 SOD1 SOD1 16 3.2 the gene encoding Cu Zn superoxide dismutase (EC EC 1.15.1.1 SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27697 17997855 32913 20996 11179 SOD1 ALS ALS 1 1.9 Clinically ALS occurs both sporadically and as a familial form 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27698 17997855 32914 20996 11179 SOD1 ALS ALS 2 1.9 In 5_amp_#x02013 10% ALS is a familial disease and approximately 20% of the familial 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27699 17997855 32914 20996 11179 SOD1 ALS ALS 13 1.9 is a familial disease and approximately 20% of the familial ALS cases are caused by a mutation in the gene encoding 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27700 17997855 32914 20996 11179 SOD1 SOD1 SOD1 24 3.2 cases are caused by a mutation in the gene encoding SOD1 4 5 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27701 17997855 32916 20996 11179 SOD1 SOD1 SOD1 14 3.2 the amino acid glycine is replaced by alanine in the SOD1 enzyme 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27702 17997855 32917 20996 11179 SOD1 ALS ALS 9 1.9 Families with the G93A-SOD1 mutation are indistinguishable from sporadic ALS by clinical and pathologic criteria 5 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27703 17997855 32918 20996 11179 SOD1 SOD1 SOD1 12 3.2 model to study the cellular alterations associated with mutations of SOD1 was constructed by transfection of the human neuroblastoma cell line 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27704 17997855 32919 20996 11179 SOD1 SOD1 SOD1 13 3.2 was chosen because it does not affect the activity of SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27705 17997855 32920 20996 11179 SOD1 ALS ALS 9 1.9 A significant inflammatory component contributes to the pathology of ALS 7 8 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27706 17997855 32921 20996 11179 SOD1 ALS ALS 17 1.9 and various cytokines and chemokines in the CNS tissue of ALS patients and mouse models 7 9 10 and the presence 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27707 17997855 32921 20996 11179 SOD1 ALS ALS 45 1.9 cells as demonstrated in post mortem spinal cord tissue of ALS patients 10 11 and by positron emission tomography using 11 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27708 17997855 32921 20996 11179 SOD1 ALS ALS 63 1.9 emission tomography using 11 C](R)-PK11195 C R -PK11195 in living ALS patients 12 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27709 17997855 32922 20996 11179 SOD1 ALS ALS 13 1.9 activated microglial cells in the vicinity of neuronal death in ALS suggests that stimulants of microglial activation are produced by stressed 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27710 17997855 32927 22217 11848 TLR2 TLR2 TLR2 35 3.7 of the innate immune system particularly Toll-like receptor 2 (TLR2) TLR2 18 19 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27711 17997855 32931 20996 11179 SOD1 SOD1 SOD1 24 3.2 neuroblastoma cell lines constitutively expressing either wild-type (Wt) Wt human SOD1 or the G93A mutant of this enzyme associated with familial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27712 17997855 32942 19573 10691 SDS SDS SDS-polyacrylamide 5 0.0 Toxin purity was assessed by SDS-polyacrylamide gel electrophoresis followed by Coomassie-blue staining which showed a single 11 JUMiner_v2.2 1 0 0 2 19440 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:19440|SBDS|0.000386094610941903<>ScoreDetail__10691|SDS|0.000132749236691889__19440|SBDS|0.000386094610941903__ 0 0 0 0 0 27713 17997855 32945 14042 7625 NA NAC NAC 3 0.0 Methods Antioxidant N-acetylcysteine (NAC) NAC To examine the effect of the antioxidant N-acetylcysteine (NAC) NAC 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27714 17997855 32945 14042 7625 NA NAC NAC 12 0.0 NAC To examine the effect of the antioxidant N-acetylcysteine (NAC) NAC (Sigma, Sigma Deisenhofen Germany on cell viability SH-SY5Y G93A-SOD1 and 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27715 17997855 32945 14042 7625 NA NAC NAC 35 0.0 neuroblastoma cells were kept in culture medium containing 1 mM NAC for periods of 24 and 72 hours prior to the 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27716 17997855 32950 3901 1693 CD68 CD68 CD-68 0 0.3 CD-68 staining showed 98_amp_#x02013 99% purity of the macrophage cultures 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27717 17997855 32956 5021 2444 CSK CSK CSK 24 0.0 Cys-SKKKK _amp_#x000d7 3 HCl EMC Microcollections Tuebingen Germany Pam 3 CSK 4 22 in concentrations of 10 _amp_#x003bc;g/ml _amp_#x003bc g ml 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27718 17997855 32957 23484 12446 TYRO3 BYK Byk 26 0.0 enzyme immunoassay (LIA) LIA using the Liaison _amp_#x000ae Analyser from Byk Sangtec and reagents from Diasorin (Dietzenbach, Dietzenbach Germany 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27719 17997855 32963 19254 10472 RUNX2 CCD CCD 10 0.0 Changes in Ca 2 i were measured using a CCD camera system (TILL TILL Photonics Martinsried Germany 23 24 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27720 17997855 32965 19254 10472 RUNX2 CCD CCD 1 0.0 The CCD camera displayed 12-bit dynamics and an A/D A D converter 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27721 17997855 32973 20247 20116 SLC25A29 CACL CaCl 12 1.0 either RPMI-1640 or (in in mM NaCl 140 KCl 2 CaCl 2 2.5 MgCl 2 1 HEPES 10 glucose 40 and 14 JUMiner_v2.2 1 2 cacl 0 0 0 0 0 0 0 0 27722 17997855 32974 20247 20116 SLC25A29 CACL CaCl 11 1.0 nominally Ca 2 -free solutions MgCl 2 was substituted for CaCl 2 without adding EGTA 14 JUMiner_v2.2 1 2 cacl 0 0 0 0 0 0 0 0 27723 17997855 32976 3901 1693 CD68 CD68 CD68 3 0.3 Methods Hemalum staining CD68 and activated caspase-3 immunocytochemistry and light green staining Pneumolysin-stimulated SH-SY5Y 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27724 17997855 32977 3901 1693 CD68 CD68 CD68 0 0.3 CD68 and light green staining was used to distinguish between human 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27725 17997855 32977 20996 11179 SOD1 SOD1 SOD1 38 3.2 activated caspase-3 was used to detect apoptosis in pneumolysin-treated G93A SOD1 cells fixated cells were permeabilised with Triton X (0.1% 0.1% 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 27726 17997855 32977 3901 1693 CD68 CD68 CD68 57 0.3 0.1% in PBS for 30 minutes and then incubated with CD68 antibody (clone clone KP1 dilution 1 50 DAKO Glostrup Denmark 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27727 17997855 32979 3901 1693 CD68 CD68 CD68 32 0.3 in a brown staining of the somata of macrophages (CD68)/apoptotic CD68 apoptotic G93A SOD1 cells (Caspase Caspase 3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27728 17997855 32979 20996 11179 SOD1 SOD1 SOD1 34 3.2 staining of the somata of macrophages (CD68)/apoptotic CD68 apoptotic G93A SOD1 cells (Caspase Caspase 3 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 27729 17997855 32980 3901 1693 CD68 CD68 CD68 17 0.3 yellowish solution (Chroma-Gesellschaft Chroma-Gesellschaft Schmidt _amp_#x00026 Co Stuttgart Germany after CD68 immunocytochemistry and with hemalum after caspase-3 immunocytochemistry for 1_amp_#x02013 2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27730 17997855 33011 14042 7625 NA NAC NAC 11 0.0 pneumolysin-induced neuronal injury was attenuated by the anti-oxidant N-acetyl-cysteine (NAC) NAC Incubation with the antioxidant N-acetyl-cysteine (NAC) NAC in a concentration 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27731 17997855 33011 14042 7625 NA NAC NAC 17 0.0 anti-oxidant N-acetyl-cysteine (NAC) NAC Incubation with the antioxidant N-acetyl-cysteine (NAC) NAC in a concentration of 1 mM starting 72 and 24 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27732 17997855 33011 14042 7625 NA NAC NAC 52 0.0 G93A-SOD1 cells compared to G93A-SOD1 cells kept in medium without NAC (difference difference not significant 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27733 17997855 33012 14042 7625 NA NAC NAC 4 0.0 After 72 hours of NAC pre-treatment pneumolysin exposure to G93A-SOD1 cells resulted in a metabolic 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27734 17997855 33012 14042 7625 NA NAC NAC 46 0.0 3.1% of respective pneumolysin-challenged G93A-SOD1 cells in the absence of NAC (p p _amp_#x0003c 0.001 (Fig Fig 9 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27735 17997855 33013 14042 7625 NA NAC NAC-containing 6 0.0 After pre-incubation of G93A-SOD1 cells in NAC-containing medium for a period of 24 hours similar results were 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27736 17997855 33013 14042 7625 NA NAC NAC 18 0.0 for a period of 24 hours similar results were observed NAC exerted a neuroprotective effect on G93A-SOD1 cells treated with pneumolysin 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27737 17997855 33013 14042 7625 NA NAC NAC 54 0.0 mitochondrial metabolic activity of control cells in G93A cells with NAC treatment versus 15.1 _amp_#x000b1 5.4% without NAC treatment p _amp_#x0003c 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27738 17997855 33013 14042 7625 NA NAC NAC 61 0.0 G93A cells with NAC treatment versus 15.1 _amp_#x000b1 5.4% without NAC treatment p _amp_#x0003c 0.0001 (Fig Fig 10 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27739 17997855 33016 14042 7625 NA NAC NAC-treated 11 0.0 there was no significant difference in the metabolic activity of NAC-treated and untreated Wt-SOD1 cells after pneumolysin incubation i.e. NAC did 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27740 17997855 33016 14042 7625 NA NAC NAC 20 0.0 of NAC-treated and untreated Wt-SOD1 cells after pneumolysin incubation i.e. NAC did not protect Wt-SOD1 neuroblastoma cells from the toxic action 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27741 17997855 33016 14042 7625 NA NAC NAC 61 0.0 6.6% in pneumolysin-exposed Wt-SOD1 cells with 72 hours pre-incubation with NAC p _amp_#x0003e 0.05 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27742 17997855 33017 22217 11848 TLR2 TLR2 TLR2 34 3.7 After stimulation of human neuroblastoma and macrophage co-cultures with the TLR2 agonist Pam 3 CSK 4 for a period of 72 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27743 17997855 33017 6640 3353 ENO2 NSE NSE 51 0.3 period of 72 hours the release of neuron-specific enolase (NSE) NSE was measured in the culture supernatants and expressed as per 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27744 17997855 33017 6640 3353 ENO2 NSE NSE 65 0.3 the culture supernatants and expressed as per cent of the NSE release induced by cell lysis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27745 17997855 33017 5021 2444 CSK CSK CSK 22 0.0 of monocytes stimulated with the Toll-like receptor-2 agonist Pam 3 CSK 4 After stimulation of human neuroblastoma and macrophage co-cultures with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27746 17997855 33017 5021 2444 CSK CSK CSK 38 0.0 neuroblastoma and macrophage co-cultures with the TLR2 agonist Pam 3 CSK 4 for a period of 72 hours the release of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27747 17997855 33018 6640 3353 ENO2 NSE NSE 13 0.3 with G93A-SOD1 SH-SY5Y cells showed a significantly higher release of NSE compared to co-cultures with Wt-SOD1 SH-SY5Y cells after stimulation with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27748 17997855 33018 5021 2444 CSK CSK CSK 26 0.0 co-cultures with Wt-SOD1 SH-SY5Y cells after stimulation with Pam 3 CSK 4 (27.8 27.8 _amp_#x000b1 2.4% vs 19.0 _amp_#x000b1 3.3% p 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27749 17997855 33026 20996 11179 SOD1 SOD1 SOD1 20 3.2 that SH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) G93A-SOD1 are more vulnerable to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27750 17997855 33026 20996 11179 SOD1 ALS ALS 24 1.9 transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) G93A-SOD1 are more vulnerable to infectious stimuli than neuroblastoma 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27751 17997855 33026 20996 11179 SOD1 SOD1 SOD1 37 3.2 more vulnerable to infectious stimuli than neuroblastoma cells overexpressing normal SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27752 17997855 33031 18312 670 RHOD Rho Rho 6 0.3 At sublytic concentrations pneumolysin rapidly activates Rho and Rac GTPases and leads to the formation of actin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27753 17997855 33031 543 391 AKT1 RAC Rac 8 0.1 At sublytic concentrations pneumolysin rapidly activates Rho and Rac GTPases and leads to the formation of actin stress fibers 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27754 17997855 33035 12337 6871 MAPK1 p38 p38 8 0.5 The massive Ca 2 influx causes activation of p38 MAPK opening of the mitochondrial permeability transition (MPT) MPT pore 1 JUMiner_v2.2 1 0 0 2 6871 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6871|MAPK1|0.00104650842166509<>ScoreDetail__1189|AHSA1|0.000159299084030267__6878|MAPK4|0.000750981396142686__6871|MAPK1|0.00104650842166509__6876|MAPK14|0.000817050140671369__ 0 0 0 0 0 27755 17997855 33035 12337 6871 MAPK1 MAPK MAPK 9 0.5 The massive Ca 2 influx causes activation of p38 MAPK opening of the mitochondrial permeability transition (MPT) MPT pore and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27756 17997855 33040 20996 11179 SOD1 SOD1 SOD1 38 3.2 than the capacity of neuroblastoma cells not transfected with mutant SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27757 17997855 33042 20996 11179 SOD1 SOD1 SOD1 24 3.2 production of reactive oxygen species in neuroblastoma cells expressing mutant SOD1 34 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27758 17997855 33050 20996 11179 SOD1 ALS ALS 10 1.9 Mitochondrial damage contributes to neuronal death both in inflammation and ALS 46 47 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27759 17997855 33051 22219 11850 TLR4 TLR4 TLR4 12 2.2 microglia has been observed in vitro following stimulation with the TLR4 agonist lipopolysaccharide (LPS) LPS 44 45 and analogues of bacterial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27760 17997855 33051 22224 15633 TLR9 TLR9 TLR9 26 1.2 (LPS) LPS 44 45 and analogues of bacterial DNA (TLR9 TLR9 agonist 13 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27761 17997855 33051 24053 12728 VWS LPS LPS 15 0.0 in vitro following stimulation with the TLR4 agonist lipopolysaccharide (LPS) LPS 44 45 and analogues of bacterial DNA (TLR9 TLR9 agonist 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27762 17997855 33053 22217 11848 TLR2 TLR2 TLR2 9 3.7 Here we demonstrate that activation of macrophages by the TLR2 agonist Pam 3 CSK 4 can also cause neuronal death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27763 17997855 33053 20996 11179 SOD1 SOD1 SOD1 40 3.2 the attack of activated immune cells than those expressing wild-type SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27764 17997855 33053 5021 2444 CSK CSK CSK 13 0.0 that activation of macrophages by the TLR2 agonist Pam 3 CSK 4 can also cause neuronal death and that neuroblastoma cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27765 17997855 33057 20996 11179 SOD1 ALS ALS 2 1.9 In inherited ALS after an initial phase of the disease predominated by motor 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00179627854242123<>ScoreDetail__5468|IGFALS|0.000471355078514289__11179|SOD1|0.00179627854242123__ 0 0 0 0 0 27766 17997855 33057 20996 11179 SOD1 SOD SOD 18 1.9 the disease predominated by motor neuron damage caused by mutant SOD in a later phase of disease progression is linked to 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27767 17997855 33059 926 620 APP amyloid amyloid 6 1.0 Co-stimulation of microglia with host-derived compounds (_amp_#x003b2;-amyloid, _amp_#x003b2 -amyloid fibronectin advanced glycation end products and bacterial products can lead 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 27768 17997855 33060 20996 11179 SOD1 SOD1 SOD1 19 3.2 increased susceptibility of neurons expressing the G93A mutant in their SOD1 to the attack of activated immune cells may be the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27769 17997855 33061 926 620 APP amyloid amyloid 8 1.0 Endogenous compounds deposited in the extracellular space (e.g., e.g. _amp_#x003b2 -amyloid 17 entering the brain through the leaky blood-brain barrier (e.g., 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 27770 17997855 33063 22217 11848 TLR2 TLR2 TLR2 10 3.7 of the monocyte/macrophage/microglia monocyte macrophage microglia type activated by a TLR2 agonist can kill neurons 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27771 17997855 33064 20996 11179 SOD1 SOD1 SOD1 4 3.2 Neuronal cells expressing a SOD1 mutant frequently encountered in familial cases of amyotrophic lateral sclerosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27772 17997855 33064 20996 11179 SOD1 SOD1 SOD1 40 3.2 attack of activated immune cells than neuronal cells expressing wild-type SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27773 17997855 33088 20996 11179 SOD1 SOD1 SOD1 15 3.2 influx into G 93A-SOD1 neuroblastoma cells in comparison to wild-type SOD1 cells 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 27774 17997855 33090 20996 11179 SOD1 SOD1 SOD1 15 3.2 influx into G 93A-SOD1 neuroblastoma cells in comparison to wild-type SOD1 cells 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 27775 17997855 33092 20996 11179 SOD1 SOD1 SOD1 15 3.2 influx into G 93A-SOD1 neuroblastoma cells in comparison to wild-type SOD1 cells 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 27776 17997855 33095 14042 7625 NA NAC NAC 24 0.0 by pre-incubation for 72 hours with the anti-oxidant N-acetylcysteine (NAC) NAC in a concentration (more more ... 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27777 17997855 33096 14042 7625 NA NAC NAC 15 0.0 N-acetyl-cysteine 24 hours of pre-incubation with the anti-oxidant N-acetylcysteine (NAC) NAC in a concentration of 1 mM also resulted in an 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>7625|NA|4663|No_GeneRif__14374|NLRP1|22861|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 27778 17997855 33097 20996 11179 SOD1 SOD1 SOD1 7 3.2 Figure 11 Vulnerability of G93A-SOD1 and wild-type SOD1 neuroblastoma cells to the attack of monocytes stimulated with Pam 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27779 17997855 33097 5021 2444 CSK CSK CSK 19 0.0 cells to the attack of monocytes stimulated with Pam 3 CSK 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27780 17997855 33098 6640 3353 ENO2 NSE NSE 13 0.3 (values values expressed in per cent _amp_#x000b1 SD of the NSE release induced by cell lysis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27781 17997855 33100 20996 11179 SOD1 SOD1 SOD1 7 3.2 Figure 12 Vulnerability of G93A-SOD1 and wild-type SOD1 neuroblastoma cells to the attack of monocytes stimulated with Pam 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27782 17997855 33100 5021 2444 CSK CSK CSK 19 0.0 cells to the attack of monocytes stimulated with Pam 3 CSK 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27783 17997855 33101 5021 2444 CSK CSK CSK 5 0.0 After staining of Pam 3 CSK 4 -stimulated co-cultures with light green and macrophage staining with 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 27784 17997855 33102 5021 2444 CSK CSK CSK 16 0.0 cells to the attack of monocytes stimulated with Pam 3 CSK 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29808 18040778 35397 11629 6493 LAMC2 CSF CSF 18 0.0 the blood-brain barrier (BBB) BBB and blood-cerebral spinal fluid (CSF) CSF barrier as well as the presence of drug-specific transporters in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29809 18040778 35411 9006 4799 HADH HAD HAD 4 0.0 HIV infection HIV-associated dementia (HAD) HAD is typically a late manifestation of HIV infection and is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29810 18040778 35412 9006 4799 HADH HAD HAD 7 0.0 A key element in the development of HAD appears to be infection of microglia which are the only 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29811 18040778 35413 9006 4799 HADH HAD HAD 18 0.0 and macrophages in the CNS is a better correlate with HAD than the presence and amount of HIV-1-infected cells in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29812 18040778 35416 9006 4799 HADH HAD HAD 26 0.0 limited compared to the diffuse CNS abnormalities that occur in HAD (Lipton Lipton and Gendelman 1995 which suggests that diffusible factors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29813 18040778 35417 22551 11892 TNF TNF TNF 21 1.2 actively secrete both neurotoxins such as tumor necrosis factor (TNF)-A, TNF -A interleukin (IL)-1B, IL -1B CXCL8 glutamate quinolinic acid platelet 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29814 18040778 35417 10470 6025 IL8 CXCL8 CXCL8 24 1.3 tumor necrosis factor (TNF)-A, TNF -A interleukin (IL)-1B, IL -1B CXCL8 glutamate quinolinic acid platelet activating factor eicosanoids and nitric oxide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29815 18040778 35419 450 330 AGRP ART ART 3 0.0 Although antiretroviral therapy (ART) ART is extremely important in the control of HIV infection its 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29816 18040778 35419 9006 4799 HADH HAD HAD 16 0.0 important in the control of HIV infection its role in HAD is less clear 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29817 18040778 35420 450 330 AGRP ART ARTs 1 0.0 Specific ARTs such as efavirenz have been shown to inhibit HIV replication 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29818 18040778 35421 10676 6121 IRF6 LPS LPS 11 0.3 indinavir and zidovudine have been shown to inhibit lipopolysaccharide (LPS)-stimulated LPS -stimulated microglial production of matrix metalloproteinase (MMP)-9, MMP -9 thereby 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 29819 18040778 35422 9006 4799 HADH HAD HAD 11 0.0 with activity against HIV may not be enough to impact HAD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29820 18040778 35423 9006 4799 HADH HAD HAD 13 0.0 microglia release neurotoxins which may ultimately be more important in HAD than viral replication per se 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29821 18040778 35424 450 330 AGRP ART ART 6 0.0 Also there is some evidence that ART itself may contribute to overall neuroinflammation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29822 18040778 35427 9006 4799 HADH HAD HAD 10 0.0 For these reasons ideal therapeutic agents for the treatment of HAD would attenuate HIV-1 neuropathogenesis through both direct inhibition of viral 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29823 18040778 35430 10676 6121 IRF6 LPS LPS-induced 16 0.3 the benzodiazepines which cross the CNS bind to microglia inhibit LPS-induced TNF-A production suppress HIV-1 Tat protein-induced chemotaxis and also inhibit 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 29824 18040778 35430 22551 11892 TNF TNFA TNF-A 17 1.2 benzodiazepines which cross the CNS bind to microglia inhibit LPS-induced TNF-A production suppress HIV-1 Tat protein-induced chemotaxis and also inhibit HIV-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29825 18040778 35431 9006 4799 HADH HAD HAD 10 0.0 These agents may yet prove to be useful in controlling HAD by targeting microglia as the central player in this process 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29826 18040778 35433 5693 2770 DES DES Des 32 0.0 subarachnoid space from an adjacent parenchymal tubercle (Leonard Leonard and Des Prez 1990 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29827 18040778 35436 14211 7685 NDUFA2 CD14 CD14 39 1.0 nonopsonized M tuberculosis by human microglia is facilitated by the CD14 receptor (Rock Rock et al. 2004 1 JUMiner_v2.2 1 0 0 2 1628 TotalCon:2<>1628|CD14|929|Complete__7685|NDUFA2|4695|Complete__<>AvaiableGeneRif=2<>BEST:1628|CD14|0.000395594233306782<>ScoreDetail__7685|NDUFA2|0.000221621995983101__1628|CD14|0.000395594233306782__ 0 0 0 0 0 29828 18040778 35438 10437 5992 IL1B IL-1 IL-1 33 1.8 that following infection there is a lasting inhibition of both IL-1 and IL-10 production (Curto Curto et al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29829 18040778 35438 10480 5962 IL10 IL-10 IL-10 35 1.3 infection there is a lasting inhibition of both IL-1 and IL-10 production (Curto Curto et al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29830 18040778 35443 22551 11892 TNF TNFA TNF-A 14 1.2 microglia elicited robust amounts of several cytokines/chemokines, cytokines chemokines including TNF-A IL-6 IL-1B CCL2 CCL5 and CXCL10 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29831 18040778 35443 10463 6018 IL6 IL-6 IL-6 15 1.6 elicited robust amounts of several cytokines/chemokines, cytokines chemokines including TNF-A IL-6 IL-1B CCL2 CCL5 and CXCL10 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29832 18040778 35443 10437 5992 IL1B IL-1B IL-1B 16 1.8 robust amounts of several cytokines/chemokines, cytokines chemokines including TNF-A IL-6 IL-1B CCL2 CCL5 and CXCL10 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29833 18040778 35443 3758 10618 CCL2 CCL2 CCL2 17 0.3 amounts of several cytokines/chemokines, cytokines chemokines including TNF-A IL-6 IL-1B CCL2 CCL5 and CXCL10 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29834 18040778 35443 3766 10632 CCL5 CCL5 CCL5 18 0.1 of several cytokines/chemokines, cytokines chemokines including TNF-A IL-6 IL-1B CCL2 CCL5 and CXCL10 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29835 18040778 35443 5198 10637 CXCL10 CXCL10 CXCL10 20 0.0 cytokines/chemokines, cytokines chemokines including TNF-A IL-6 IL-1B CCL2 CCL5 and CXCL10 1 JUMiner_v2.2 1 1 LongSymbol 0 0 0 0 0 0 0 0 29836 18040778 35453 3763 10630 CCL4 CCL4 CCL4 11 1.0 in the presence of specific antibody human microglia produce CCL3 CCL4 CCL2 CXCL8 and low levels of CCL5 via Fc-receptor activation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29837 18040778 35453 10470 6025 IL8 CXCL8 CXCL8 13 1.3 presence of specific antibody human microglia produce CCL3 CCL4 CCL2 CXCL8 and low levels of CCL5 via Fc-receptor activation (Goldman Goldman 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29838 18040778 35453 3759 10627 CCL3 CCL3 CCL3 10 0.2 Also in the presence of specific antibody human microglia produce CCL3 CCL4 CCL2 CXCL8 and low levels of CCL5 via Fc-receptor 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29839 18040778 35453 3758 10618 CCL2 CCL2 CCL2 12 0.4 the presence of specific antibody human microglia produce CCL3 CCL4 CCL2 CXCL8 and low levels of CCL5 via Fc-receptor activation (Goldman 5 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29840 18040778 35453 3766 10632 CCL5 CCL5 CCL5 18 0.0 microglia produce CCL3 CCL4 CCL2 CXCL8 and low levels of CCL5 via Fc-receptor activation (Goldman Goldman et al. 2001 1 JUMiner_v2.2 1 1 ccl5; 0 0 0 0 0 0 0 0 29841 18040778 35462 9947 5468 IGFALS ALS ALS 54 0.3 (Cagnin Cagnin et al. 2001 and amyotrophic lateral sclerosis (ALS) ALS (Turner Turner et al. 2004 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00072716234739917<>ScoreDetail__5468|IGFALS|0.000246042811449192__11179|SOD1|0.00072716234739917__ 0 0 0 0 0 29842 18040778 35466 9947 5468 IGFALS ALS ALS 37 0.3 neurodegenerative processes in MS AD Parkinson's disease (PD), PD and ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00072716234739917<>ScoreDetail__5468|IGFALS|0.000246042811449192__11179|SOD1|0.00072716234739917__ 0 0 0 0 0 29843 18040778 35467 926 620 APP amyloid amyloid 32 1.0 or endogenous proteins that have taken on pathological properties e.g. amyloid B peptide (AB) AB in AD and A-synuclein in PD 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 29844 18040778 35471 10676 6121 IRF6 LPS LPS 1 0.3 Lipopolysaccharide (LPS), LPS tumor necrosis factor (TNF)-A, TNF -A reactive oxygen intermediates (ROI), 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 29845 18040778 35471 22551 11892 TNF TNF TNF 5 1.2 Lipopolysaccharide (LPS), LPS tumor necrosis factor (TNF)-A, TNF -A reactive oxygen intermediates (ROI), ROI reactive nitrogen intermediates (RNI), 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29846 18040778 35471 9947 5468 IGFALS ALS ALS 29 0.3 (AD), AD Parkinson's disease (PD), PD amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00072716234739917<>ScoreDetail__5468|IGFALS|0.000246042811449192__11179|SOD1|0.00072716234739917__ 0 0 0 0 0 29847 18040778 35484 3865 1678 CD4 CD4 CD4 28 0.3 block neurogenesis microglia activated by interleukin-4 or interferon-G associated with CD4 lymphocyte infiltration induces neurogenesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29848 18040778 35498 17610 9605 PTGS2 COX-2 COX-2 1 1.0 Cyclooxygenase-2 (COX-2) COX-2 is an enzyme central to the production of prostaglandins a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29849 18040778 35499 17610 9605 PTGS2 COX-2 COX-2 0 1.0 COX-2 and prostaglandin E 2 are elevated in the CNS of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29850 18040778 35499 9947 5468 IGFALS ALS ALS 13 0.3 E 2 are elevated in the CNS of patients with ALS and recent studies have implicated activated microglia in this _amp_#8220 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00072716234739917<>ScoreDetail__5468|IGFALS|0.000246042811449192__11179|SOD1|0.00072716234739917__ 0 0 0 0 0 29851 18040778 35500 17610 9605 PTGS2 COX-2 COX-2 15 1.0 implicated in other neuroinflammatory/neurodegenerative neuroinflammatory neurodegenerative diseases and not surprisingly COX-2 has been considered a major therapeutic target 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29852 18040778 35501 9947 5468 IGFALS ALS ALS 61 0.3 in development of new treatments of AD PD MS and ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00072716234739917<>ScoreDetail__5468|IGFALS|0.000246042811449192__11179|SOD1|0.00072716234739917__ 0 0 0 0 0 29853 18040778 35505 17610 9605 PTGS2 COX-2 COX-2 8 1.0 Hypothetically by inhibiting microglial cell cyclooxygenases (COX-1 COX-1 or COX-2 the metabolism of arachadonic acid is curtailed and production of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29854 18040778 35505 17609 9604 PTGS1 COX-1 COX-1 6 0.1 Hypothetically by inhibiting microglial cell cyclooxygenases (COX-1 COX-1 or COX-2 the metabolism of arachadonic acid is curtailed and 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29855 18040778 35506 17610 9605 PTGS2 COX COX 8 0.0 In addition to the suppression of prostaglandin production COX inhibitors may also decrease the formation of AB peptide (Hirohata 1 JUMiner_v2.2 1 1 UserEdit 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 1 1 4829 2294 COX8A 1 cox; 29856 18040778 35507 17610 9605 PTGS2 COX-2 COX-2 8 1.0 Although preclinical and early clinical data suggested that COX-2 inhibitors may have a beneficial role in AD results of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29857 18040778 35507 17610 9605 PTGS2 COX-2 COX-2 29 1.0 subsequent studies and the development of unanticipated side effects of COX-2 inhibitors have dampened enthusiasm for the use of these agents 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29858 18040778 35510 22551 11892 TNF TNFA TNF-A 28 1.2 NO production as well as to suppress the production of TNF-A by LPS and AB peptide-stimulated microglia (Dheen Dheen et al. 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 29859 18040778 35510 10676 6121 IRF6 LPS LPS 30 0.3 as well as to suppress the production of TNF-A by LPS and AB peptide-stimulated microglia (Dheen Dheen et al. 2005 moreover 1 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 29860 18040778 35514 9947 5468 IGFALS ALS ALS 3 0.3 Of relevance to ALS a drug screening program recently revealed that ceftriaxone modulates glutamate 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00072716234739917<>ScoreDetail__5468|IGFALS|0.000246042811449192__11179|SOD1|0.00072716234739917__ 0 0 0 0 0 29861 18040778 35514 9947 5468 IGFALS ALS ALS 27 0.3 neurons both in vitro and in an animal model of ALS (Rothstein Rothstein et al. 2005 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00072716234739917<>ScoreDetail__5468|IGFALS|0.000246042811449192__11179|SOD1|0.00072716234739917__ 0 0 0 0 0 29862 18040778 35518 22551 11892 TNF TNFA TNF-A 7 1.2 Although early studies have shown that microglia-derived TNF-A induces apoptosis of hippocampal progenitor cells (Cacci Cacci et al. 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24978 18246426 29675 20996 11179 SOD1 ALS ALS 12 0.0 of cytokines in the pathophysiology of amyotrophic lateral sclerosis (ALS) ALS and its relation to clinical outcome has not been clearly 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 24979 18246426 29676 22551 11892 TNF TNFA TNF-A 5 1.7 We evaluated tumor necrosis factor-alpha (TNF-A), TNF-A interferon-G (IFN-G) IFN-G and nitric oxide (NO) NO levels in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24980 18246426 29676 9905 5438 IFNG IFNG IFN-G 7 0.8 We evaluated tumor necrosis factor-alpha (TNF-A), TNF-A interferon-G (IFN-G) IFN-G and nitric oxide (NO) NO levels in the serum of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24981 18246426 29676 20996 11179 SOD1 ALS ALS 18 0.0 nitric oxide (NO) NO levels in the serum of 22 ALS patients and 20 controls 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 24982 18246426 29677 22551 11892 TNF TNFA TNF-A 1 1.7 Serum TNF-A levels and IFN-G levels were significantly ( P _lt_ 0.001 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24983 18246426 29677 9905 5438 IFNG IFNG IFN-G 4 0.8 Serum TNF-A levels and IFN-G levels were significantly ( P _lt_ 0.001 elevated in ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24984 18246426 29677 20996 11179 SOD1 ALS ALS 14 0.0 IFN-G levels were significantly ( P _lt_ 0.001 elevated in ALS patients 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 24985 18246426 29679 20996 11179 SOD1 ALS ALS 9 0.0 We further noticed positive correlation between the duration of ALS and these proinflammatory molecule levels 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 24986 18246426 29680 20996 11179 SOD1 ALS ALS 16 0.0 to play a crucial role in the neurodegeneration observed in ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 24987 18246426 29681 22551 11892 TNF TNFA TNF-A 4 1.7 Since high levels of TNF-A are known to be cytotoxic it could be that a 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24988 18246426 29681 20996 11179 SOD1 ALS ALS 30 0.0 may be one of the factors underlying the progression of ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 24989 18246426 29682 20996 11179 SOD1 ALS ALS 8 0.0 This study confirms the involvement of inflammation in ALS and the need to develop surrogate markers to check the 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 24990 18246426 29684 20996 11179 SOD1 ALS ALS 4 0.0 Introduction Amyotrophic lateral sclerosis (ALS), ALS which is progressive and usually runs a fatal course within 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 24991 18246426 29685 20996 11179 SOD1 ALS ALS 4 0.0 The underlying cause of ALS is not well known but familial environmental viral metabolic and 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 24992 18246426 29689 20996 11179 SOD1 ALS ALS 16 0.0 levels were significantly higher in a group of northern indian ALS patients 9 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 24993 18246426 29690 22551 11892 TNF TNFA TNF-A 10 1.7 role of proinflammatory cytokines such as tumor necrosis factor-A (TNF-A) TNF-A and interferon-G (IFN-G) IFN-G as potential mediators during the progression 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24994 18246426 29690 9905 5438 IFNG IFNG IFN-G 13 0.8 such as tumor necrosis factor-A (TNF-A) TNF-A and interferon-G (IFN-G) IFN-G as potential mediators during the progression of brain injury is 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24995 18246426 29692 22551 11892 TNF TNFA TNF-A 0 1.7 TNF-A is essential to orchestrate the immune response in the brain 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24996 18246426 29693 22551 11892 TNF TNFA TNF-A 8 1.7 The duration of the response and levels of TNF-A in the cerebral environment may be the critical factors for 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24997 18246426 29694 22551 11892 TNF TNFA TNF-A 4 1.7 The detrimental effects of TNF-A in the CNS may also depend on the presence of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24998 18246426 29695 22551 11892 TNF TNFA TNF-A 9 1.7 Ag stimulated T cells have the ability to produce TNF-A along with IFN-G that acts in both innate and specific 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 24999 18246426 29695 9905 5438 IFNG IFNG IFN-G 12 0.8 T cells have the ability to produce TNF-A along with IFN-G that acts in both innate and specific cell-mediated immunities 16 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25000 18246426 29696 22551 11892 TNF TNFA TNF-A 4 1.7 The mixture of both TNF-A and IFN-G may therefore be harmful to neuronal elements 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25001 18246426 29696 9905 5438 IFNG IFNG IFN-G 6 0.8 The mixture of both TNF-A and IFN-G may therefore be harmful to neuronal elements 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25002 18246426 29697 9905 5438 IFNG IFNG IFN-G 6 0.8 In this regard transgenic mice expressing IFN-G in hippocampus exhibit profound enhanced microglial reactivity to lesion-induced neuronal 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25003 18246426 29697 9905 5438 IFNG IFNG IFN-G 20 0.8 profound enhanced microglial reactivity to lesion-induced neuronal injury indicating that IFN-G acts as an amplifier of the response 17 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25004 18246426 29698 9905 5438 IFNG IFNG IFN-G 5 0.8 Four days of treatment with IFN-G failed to alter cell survival or myelin basic protein gene 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25005 18246426 29698 22551 11892 TNF TNFA TNF-A 38 1.7 Fas-mediated apoptosis and this effect is augmented in presence of TNF-A 18 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25006 18246426 29700 14533 7872 NOS1 NOS NOS 10 2.7 is synthesized from l -arginine by nitric oxide synthase (NOS) NOS 22 23 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000827888698638064<>ScoreDetail__7873|NOS2A|0.000827888698638064__7872|NOS1|0.000827445524948527__ 0 0 0 0 0 25007 18246426 29701 14533 7872 NOS1 NOS NOS 6 2.7 Within the CNS two isoforms of NOS exist calcium dependent neuronal form (nNOS) nNOS and inducible calcium 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000827888698638064<>ScoreDetail__7873|NOS2A|0.000827888698638064__7872|NOS1|0.000827445524948527__ 0 0 0 0 0 25008 18246426 29701 14533 7872 NOS1 nNOS nNOS 12 2.7 two isoforms of NOS exist calcium dependent neuronal form (nNOS) nNOS and inducible calcium independent form (iNOS) iNOS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25009 18246426 29701 14535 7873 NOS2A iNOS iNOS 18 2.7 neuronal form (nNOS) nNOS and inducible calcium independent form (iNOS) iNOS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25010 18246426 29702 14533 7872 NOS1 nNOS nNOS 5 2.7 Under normal conditions neurons containing nNOS release relatively small quantities of NO which has neurotransmitter like 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25011 18246426 29703 22551 11892 TNF TNFA TNF-A 12 1.7 of this study is to measure the systemic inflammatory markers TNF-A IFN-G and nitric oxide in ALS patients and evaluate their 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25012 18246426 29703 9905 5438 IFNG IFNG IFN-G 13 0.8 this study is to measure the systemic inflammatory markers TNF-A IFN-G and nitric oxide in ALS patients and evaluate their role 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25013 18246426 29703 20996 11179 SOD1 ALS ALS 18 0.0 the systemic inflammatory markers TNF-A IFN-G and nitric oxide in ALS patients and evaluate their role in the prognosis of this 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25014 18246426 29705 20996 11179 SOD1 ALS ALS 0 0.0 ALS patients and control subjects This is a tertiary referral-hospital based 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25015 18246426 29706 20996 11179 SOD1 ALS ALS 0 0.0 ALS patients were recruited from outpatients using El Escorial diagnostic criteria 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25016 18246426 29708 20996 11179 SOD1 ALS ALS 3 0.0 Patients diagnosed with ALS also met an extensive list of exclusionary criteria including sensory 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25017 18246426 29708 20996 11179 SOD1 ALS ALS 28 0.0 bladder changes and metabolic or toxic disorder that could mimic ALS e.g. myelopathy lead intoxication endocrine abnormalities or peripheral neuropathy 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25018 18246426 29709 20996 11179 SOD1 ALS ALS 7 0.0 Twenty-two patients were diagnosed as having sporadic ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25019 18246426 29715 12527 9234 MED1 PBP PBP 11 0.6 these patients were diagnosed as having progressive bulbar palsy (PBP), PBP which results from exclusive lower motor neuron involvement in bulbar 1 JUMiner_v2.2 1 2 UserEdit 0 2 9240 TotalCon:5<>8630|PEBP1|5037|Complete__2989|DOCK3|1795|Complete__9234|MED1|5469|Complete__9008|PKD1|5310|Complete__9240|PPBP|5473|Complete__<>AvaiableGeneRif=5<>BEST:9240|PPBP|0.000751566220115642<>ScoreDetail__9234|MED1|0.000574762661096727__9008|PKD1|0.000448804005918725__8630|PEBP1|0.000596132816928709__2989|DOCK3|0.000427899015832264__9240|PPBP|0.000751566220115642__ 1 1 0 0 0 25020 18246426 29716 12527 9234 MED1 PBP PBP 1 0.6 These PBP patients were having tongue fasciculations and swallowing difficulty but their 1 JUMiner_v2.2 1 2 UserEdit 0 2 9240 TotalCon:5<>8630|PEBP1|5037|Complete__2989|DOCK3|1795|Complete__9234|MED1|5469|Complete__9008|PKD1|5310|Complete__9240|PPBP|5473|Complete__<>AvaiableGeneRif=5<>BEST:9240|PPBP|0.000751566220115642<>ScoreDetail__9234|MED1|0.000574762661096727__9008|PKD1|0.000448804005918725__8630|PEBP1|0.000596132816928709__2989|DOCK3|0.000427899015832264__9240|PPBP|0.000751566220115642__ 1 1 0 0 0 25021 18246426 29721 20996 11179 SOD1 ALS ALS 9 0.0 We were interested in testing the immunologic pathogenesis for ALS as has been recently proposed hence we only included 20 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25022 18246426 29728 22551 11892 TNF TNFA TNF-A 0 1.7 TNF-A and IFN-G assay The serum thus obtained was stored at 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25023 18246426 29728 9905 5438 IFNG IFNG IFN-G 2 0.8 TNF-A and IFN-G assay The serum thus obtained was stored at _amp_#8722 80C 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25024 18246426 29728 22551 11892 TNF TNFA TNF-A 16 1.7 obtained was stored at _amp_#8722 80C and was used for TNF-A and IFN-G estimation by ELISA 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25025 18246426 29728 9905 5438 IFNG IFNG IFN-G 18 0.8 stored at _amp_#8722 80C and was used for TNF-A and IFN-G estimation by ELISA 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25026 18246426 29729 11629 6493 LAMC2 CSF CSF 4 0.0 We have not obtained CSF from patients and controls due to ethical considerations 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25027 18246426 29730 22551 11892 TNF TNFA TNF-A 6 1.7 Elisa kits for the estimation of TNF-A and IFN-G were obtained from R_amp_D Systems Minneapolis MN USA 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25028 18246426 29730 9905 5438 IFNG IFNG IFN-G 8 0.8 Elisa kits for the estimation of TNF-A and IFN-G were obtained from R_amp_D Systems Minneapolis MN USA 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25029 18246426 29742 20996 11179 SOD1 ALS ALS 24 0.0 values of these cytokines in control subjects and patients with ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25030 18246426 29746 22551 11892 TNF TNFA TNF-A 6 1.7 It may be noted that serum TNF-A levels in ALS patients were significantly higher ( P _lt_ 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25031 18246426 29746 20996 11179 SOD1 ALS ALS 9 0.0 It may be noted that serum TNF-A levels in ALS patients were significantly higher ( P _lt_ 0.001 with respect 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25032 18246426 29747 9905 5438 IFNG IFNG IFN-G 13 0.8 noticed a significant elevation ( P _lt_ 0.001 in serum IFN-G NO levels in ALS patients versus controls (Figs Figs 2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25033 18246426 29747 20996 11179 SOD1 ALS ALS 17 0.0 ( P _lt_ 0.001 in serum IFN-G NO levels in ALS patients versus controls (Figs Figs 2 3 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25034 18246426 29748 22551 11892 TNF TNFA TNF-A 4 1.7 Fig 1 Serum mean TNF-A (pg/ml pg ml SEM levels in ALS patients ( n 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25035 18246426 29748 20996 11179 SOD1 ALS ALS 9 0.0 1 Serum mean TNF-A (pg/ml pg ml SEM levels in ALS patients ( n = 22 and controls ( n = 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25036 18246426 29749 9905 5438 IFNG IFNG IFN-G 4 0.8 Fig 2 Serum mean IFN-G (pg/ml pg ml SEM levels in ALS patients ( n 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25037 18246426 29749 20996 11179 SOD1 ALS ALS 9 0.0 2 Serum mean IFN-G (pg/ml pg ml SEM levels in ALS patients ( n = 22 and controls ( n = 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25038 18246426 29750 20996 11179 SOD1 ALS ALS 11 0.0 NO (_amp_#956;Mol/ml _amp_#956 Mol ml of blood SEM levels in ALS patients ( n = 22 and controls ( n = 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25039 18246426 29751 22551 11892 TNF TNFA TNF-A 10 1.7 Furthermore it can be seen that in ALS patients serum TNF-A IFN-G and NO levels (Figs Figs 4 -6 respectively started 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25040 18246426 29751 9905 5438 IFNG IFNG IFN-G 11 0.8 it can be seen that in ALS patients serum TNF-A IFN-G and NO levels (Figs Figs 4 -6 respectively started to 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25041 18246426 29751 20996 11179 SOD1 ALS ALS 7 0.0 Furthermore it can be seen that in ALS patients serum TNF-A IFN-G and NO levels (Figs Figs 4 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25042 18246426 29753 22551 11892 TNF TNFA TNF-A 10 1.7 Fig 4 Second degree polynomial regression plot showing serum mean TNF-A (pg/ml pg ml SEM levels versus duration of illness in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25043 18246426 29753 20996 11179 SOD1 ALS ALS 22 0.0 SEM levels versus duration of illness in the patients of ALS ( n = 12 at 6 months 5 at 12 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25044 18246426 29755 9905 5438 IFNG IFNG IFN-G 8 0.8 Fig 5 Second degree polynomial regression plot showing IFN-G levels (pg/ml pg ml SEM versus duration of illness in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25045 18246426 29755 20996 11179 SOD1 ALS ALS 20 0.0 ml SEM versus duration of illness in the patients of ALS ( n = 12 at 6 months 5 at 12 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25046 18246426 29757 20996 11179 SOD1 ALS ALS 22 0.0 blood SEM versus duration of illness in the patients of ALS ( n = 12 at 6 months 5 at 12 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25047 18246426 29760 20996 11179 SOD1 ALS ALS 0 0.0 ALS occurs more commonly in men than in women and women 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25048 18246426 29761 20996 11179 SOD1 ALS ALS 20 0.0 to whether estrogen may be neuroprotective in delaying or preventing ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25049 18246426 29762 10463 6018 IL6 IL-6 IL-6 25 1.3 a result of its anti-inflammatory action on cytokines such as IL-6 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25050 18246426 29763 22551 11892 TNF TNFA TNF-A 10 1.7 In the present study we observed significant elevation in serum TNF-A and IFN-G levels in ALS patients and also this increase 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25051 18246426 29763 9905 5438 IFNG IFNG IFN-G 12 0.8 present study we observed significant elevation in serum TNF-A and IFN-G levels in ALS patients and also this increase was most 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25052 18246426 29763 20996 11179 SOD1 ALS ALS 15 0.0 observed significant elevation in serum TNF-A and IFN-G levels in ALS patients and also this increase was most prominent at 24 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25053 18246426 29765 10463 6018 IL6 IL-6 IL-6 7 1.3 Moreau et al 29 measured IL-6 and TNF-A in patients with ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25054 18246426 29765 22551 11892 TNF TNFA TNF-A 9 1.7 Moreau et al 29 measured IL-6 and TNF-A in patients with ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25055 18246426 29765 20996 11179 SOD1 ALS ALS 13 0.0 et al 29 measured IL-6 and TNF-A in patients with ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25056 18246426 29766 20996 11179 SOD1 ALS ALS 13 0.0 elevated levels to a normal response to hypoxemia rather than ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25057 18246426 29767 22551 11892 TNF TNFA TNF-A 14 1.7 none of the patients including the five patients in whom TNF-A levels peaked at 24 months were having any significant respiratory 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25058 18246426 29768 20996 11179 SOD1 ALS ALS 17 0.0 five patients died around 25 months from the onset of ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25059 18246426 29769 22551 11892 TNF TNFA TNF-A 6 1.7 The source for the increased serum TNF-A and IFN-G in the present study could be peripheral immune 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25060 18246426 29769 9905 5438 IFNG IFNG IFN-G 8 0.8 The source for the increased serum TNF-A and IFN-G in the present study could be peripheral immune cells 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25061 18246426 29770 22551 11892 TNF TNFA TNF-A 17 1.7 et al 30 did not find any correlation between blood TNF-A levels and duration of the disease in ALS patients 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25062 18246426 29770 20996 11179 SOD1 ALS ALS 25 0.0 between blood TNF-A levels and duration of the disease in ALS patients 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25063 18246426 29771 22551 11892 TNF TNFA TNF-A 10 1.7 Moreover Holmoy et al 31 could not detect TNF-A and IFN-G levels in the CSF of ALS patients using 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25064 18246426 29771 9905 5438 IFNG IFNG IFN-G 12 0.8 Moreover Holmoy et al 31 could not detect TNF-A and IFN-G levels in the CSF of ALS patients using a cytometric 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25065 18246426 29771 11629 6493 LAMC2 CSF CSF 16 0.0 31 could not detect TNF-A and IFN-G levels in the CSF of ALS patients using a cytometric bead assay 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25066 18246426 29771 20996 11179 SOD1 ALS ALS 18 0.0 not detect TNF-A and IFN-G levels in the CSF of ALS patients using a cytometric bead assay 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25067 18246426 29772 20996 11179 SOD1 ALS ALS 15 0.0 could be due to several factors including geographical pattern of ALS methodology antigenic versus biological response etc 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25068 18246426 29774 14533 7872 NOS1 NOS NOS 10 2.7 Considering that NO levels correlate closely with the activity of NOS in brain 34 the pronounced increases found in ALS patients 1 JUMiner_v2.2 1 0 0 2 7873 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7873|NOS2A|0.000827888698638064<>ScoreDetail__7873|NOS2A|0.000827888698638064__7872|NOS1|0.000827445524948527__ 0 0 0 0 0 25069 18246426 29774 20996 11179 SOD1 ALS ALS 21 0.0 of NOS in brain 34 the pronounced increases found in ALS patients may also suggest a role for NO in the 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25070 18246426 29776 20996 11179 SOD1 ALS ALS 28 0.0 the patients due to significant morbidity and mortality associated with ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25071 18246426 29777 22551 11892 TNF TNFA TNF-A 3 1.7 To conclude serum TNF-A and IFN-G levels peaked around 24 months from the onset 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25072 18246426 29777 9905 5438 IFNG IFNG IFN-G 5 0.8 To conclude serum TNF-A and IFN-G levels peaked around 24 months from the onset in these 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 25073 18246426 29777 20996 11179 SOD1 ALS ALS 16 0.0 levels peaked around 24 months from the onset in these ALS patients and it may be that systemic inflammation noticed could 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 25074 18246426 29778 20996 11179 SOD1 ALS ALS 11 0.0 the exact role of this observation in the pathogenesis of ALS and its correlation to neuroinflammation and neurodegeneration needs a rigorous 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.00103658273225932<>ScoreDetail__5468|IGFALS|0.00103658273225932__11179|SOD1|0.000659654298654437__ 0 0 0 0 0 15940 18312546 18852 17034 9236 PPARG PPARG PPARgamma 3 1.2 Effects of the PPARgamma activator pioglitazone on p38 MAP kinase and IkappaBalpha in the 12 JUMiner_v2.2 1 0 0 2 16039 TotalCon:2<>9236|PPARG|5468|Complete__16039|ANGPTL4|51129|Complete__<>AvaiableGeneRif=2<>BEST:16039|ANGPTL4|0.000896409987319078<>ScoreDetail__9236|PPARG|0.000619865084025719__16039|ANGPTL4|0.000896409987319078__ 0 0 0 0 0 15941 18312546 18852 12337 6871 MAPK1 p38 p38 7 1.7 Effects of the PPARgamma activator pioglitazone on p38 MAP kinase and IkappaBalpha in the spinal cord of a 1 JUMiner_v2.2 1 0 0 2 6876 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6876|MAPK14|0.000546283222507834<>ScoreDetail__1189|AHSA1|0.000224466891133558__6878|MAPK4|0.000432900432900433__6871|MAPK1|0.000468016418936664__6876|MAPK14|0.000546283222507834__ 0 0 0 0 0 15942 18312546 18852 12337 6871 MAPK1 MAP MAP 8 1.7 Effects of the PPARgamma activator pioglitazone on p38 MAP kinase and IkappaBalpha in the spinal cord of a transgenic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 15943 18312546 18853 20996 11179 SOD1 ALS ALS 15 1.4 programmed cell death and inflammation in amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00122970320456855<>ScoreDetail__5468|IGFALS|0.000393226670598933__11179|SOD1|0.00122970320456855__ 0 0 0 0 0 15944 18312546 18854 17034 9236 PPARG PPARG PPARgamma 11 1.2 molecular pathological effects of the anti-inflammatory peroxisome proliferator-activated receptor-gamma (PPARgamma) PPARgamma agonist pioglitazone in ALS we verified changes in the population 12 JUMiner_v2.2 1 0 0 2 16039 TotalCon:2<>9236|PPARG|5468|Complete__16039|ANGPTL4|51129|Complete__<>AvaiableGeneRif=2<>BEST:16039|ANGPTL4|0.000896409987319078<>ScoreDetail__9236|PPARG|0.000619865084025719__16039|ANGPTL4|0.000896409987319078__ 0 0 0 0 0 15945 18312546 18854 20996 11179 SOD1 ALS ALS 15 1.4 the anti-inflammatory peroxisome proliferator-activated receptor-gamma (PPARgamma) PPARgamma agonist pioglitazone in ALS we verified changes in the population of neurons astrocytes and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00122970320456855<>ScoreDetail__5468|IGFALS|0.000393226670598933__11179|SOD1|0.00122970320456855__ 0 0 0 0 0 15946 18312546 18854 20996 11179 SOD1 SOD1 SOD1 53 1.4 carrying a transgene for G93A mutant human superoxide dismutase-1 (SOD1) SOD1 (ALS ALS mice and non-transgenic littermates (control control mice performed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 15947 18312546 18854 20996 11179 SOD1 ALS ALS 54 1.4 transgene for G93A mutant human superoxide dismutase-1 (SOD1) SOD1 (ALS ALS mice and non-transgenic littermates (control control mice performed immunohistochemical and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00122970320456855<>ScoreDetail__5468|IGFALS|0.000393226670598933__11179|SOD1|0.00122970320456855__ 0 0 0 0 0 15948 18312546 18854 17034 9236 PPARG PPARG PPARgamma 67 1.2 littermates (control control mice performed immunohistochemical and immunoblot analyses of PPARgamma active form of phosphorylated p38 mitogen-activated protein kinase (p-p38) p-p38 12 JUMiner_v2.2 1 0 0 2 16039 TotalCon:2<>9236|PPARG|5468|Complete__16039|ANGPTL4|51129|Complete__<>AvaiableGeneRif=2<>BEST:16039|ANGPTL4|0.000896409987319078<>ScoreDetail__9236|PPARG|0.000619865084025719__16039|ANGPTL4|0.000896409987319078__ 0 0 0 0 0 15949 18312546 18854 12337 6871 MAPK1 p38 p38 72 1.7 immunohistochemical and immunoblot analyses of PPARgamma active form of phosphorylated p38 mitogen-activated protein kinase (p-p38) p-p38 and inhibitor of nuclear factor-kappaB 1 JUMiner_v2.2 1 0 0 2 6876 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6876|MAPK14|0.000546283222507834<>ScoreDetail__1189|AHSA1|0.000224466891133558__6878|MAPK4|0.000432900432900433__6871|MAPK1|0.000468016418936664__6876|MAPK14|0.000546283222507834__ 0 0 0 0 0 15950 18312546 18854 14352 7794 NFKB1 NF-kappaB NF-kappaB 82 0.6 protein kinase (p-p38) p-p38 and inhibitor of nuclear factor-kappaB (NF-kappaB)-alpha NF-kappaB -alpha (IkappaBalpha) IkappaBalpha in the spinal cords and compared the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 15951 18312546 18855 20996 11179 SOD1 ALS ALS 20 1.4 significantly lower in the non-treated groups of presymptomatic and advanced ALS mice than in the non-treated groups of age-matched control mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00122970320456855<>ScoreDetail__5468|IGFALS|0.000393226670598933__11179|SOD1|0.00122970320456855__ 0 0 0 0 0 15952 18312546 18855 8254 4235 GFAP GFAP GFAP-immunoreactive 42 0.3 was recovered with pioglitazone treatment and that optical densities of GFAP-immunoreactive astrocytes and Iba1-immunoreactive microglia were significantly higher in the non-treated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 15953 18312546 18855 479 352 AIF1 IBA1 Iba1-immunoreactive 45 1.3 pioglitazone treatment and that optical densities of GFAP-immunoreactive astrocytes and Iba1-immunoreactive microglia were significantly higher in the non-treated group of advanced 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 15954 18312546 18855 20996 11179 SOD1 ALS ALS 56 1.4 microglia were significantly higher in the non-treated group of advanced ALS mice than in the non-treated group of control mice and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00122970320456855<>ScoreDetail__5468|IGFALS|0.000393226670598933__11179|SOD1|0.00122970320456855__ 0 0 0 0 0 15955 18312546 18856 17034 9236 PPARG PPARG PPARgamma 6 1.2 Immunohistochemical analysis demonstrated that immunoreactivities for PPARgamma and p-p38 were mainly localized in neurons and that IkappaBalpha 12 JUMiner_v2.2 1 0 0 2 16039 TotalCon:2<>9236|PPARG|5468|Complete__16039|ANGPTL4|51129|Complete__<>AvaiableGeneRif=2<>BEST:16039|ANGPTL4|0.000896409987319078<>ScoreDetail__9236|PPARG|0.000619865084025719__16039|ANGPTL4|0.000896409987319078__ 0 0 0 0 0 15956 18312546 18857 17034 9236 PPARG PPARG PPARgamma-immunoreactive 13 1.2 that pioglitazone treatment resulted in no significant change in nuclear PPARgamma-immunoreactive density a significant decrease in cytosolic p-p38-immunoreactive density and a 12 JUMiner_v2.2 1 0 0 2 16039 TotalCon:2<>9236|PPARG|5468|Complete__16039|ANGPTL4|51129|Complete__<>AvaiableGeneRif=2<>BEST:16039|ANGPTL4|0.000896409987319078<>ScoreDetail__9236|PPARG|0.000619865084025719__16039|ANGPTL4|0.000896409987319078__ 0 0 0 0 0 15957 18312546 18858 12337 6871 MAPK1 p38 p38-mediated 9 1.7 Our results suggest that pioglitazone protects motor neurons against p38-mediated neuronal death and NF-kappaB-mediated glial inflammation via a PPARgamma-independent mechanism 1 JUMiner_v2.2 1 0 0 2 6876 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6876|MAPK14|0.000546283222507834<>ScoreDetail__1189|AHSA1|0.000224466891133558__6878|MAPK4|0.000432900432900433__6871|MAPK1|0.000468016418936664__6876|MAPK14|0.000546283222507834__ 0 0 0 0 0 15958 18312546 18858 14352 7794 NFKB1 NF-kappaB NF-kappaB-mediated 13 0.6 that pioglitazone protects motor neurons against p38-mediated neuronal death and NF-kappaB-mediated glial inflammation via a PPARgamma-independent mechanism 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 15959 18312546 18858 17034 9236 PPARG PPARG PPARgamma-independent 18 1.2 against p38-mediated neuronal death and NF-kappaB-mediated glial inflammation via a PPARgamma-independent mechanism 12 JUMiner_v2.2 1 0 0 2 16039 TotalCon:2<>9236|PPARG|5468|Complete__16039|ANGPTL4|51129|Complete__<>AvaiableGeneRif=2<>BEST:16039|ANGPTL4|0.000896409987319078<>ScoreDetail__9236|PPARG|0.000619865084025719__16039|ANGPTL4|0.000896409987319078__ 0 0 0 0 0 19002 18370853 22358 20996 11179 SOD1 ALS ALS 3 2.4 Amyotrophic lateral sclerosis (ALS) ALS is a late-onset progressive degeneration of motor neurons occurring both 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00227846138246539<>ScoreDetail__5468|IGFALS|0.000577151587166865__11179|SOD1|0.00227846138246539__ 0 0 0 0 0 19003 18370853 22359 20996 11179 SOD1 ALS ALS 3 2.4 The etiology of ALS remains unknown but one fifth of instances are due to 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00227846138246539<>ScoreDetail__5468|IGFALS|0.000577151587166865__11179|SOD1|0.00227846138246539__ 0 0 0 0 0 19004 18370853 22359 20996 11179 SOD1 SOD1 SOD1 33 2.4 the gene coding for Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19005 18370853 22360 20996 11179 SOD1 ALS ALS 4 2.4 Because sporadic and familial ALS affect the same neurons with similar pathology it is hoped 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00227846138246539<>ScoreDetail__5468|IGFALS|0.000577151587166865__11179|SOD1|0.00227846138246539__ 0 0 0 0 0 19006 18370853 22361 20996 11179 SOD1 SOD1 SOD1 13 2.4 evidence has been collected in rodents made transgenic for mutant SOD1 which represent the best available models for familial ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19007 18370853 22361 20996 11179 SOD1 ALS ALS 22 2.4 mutant SOD1 which represent the best available models for familial ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00227846138246539<>ScoreDetail__5468|IGFALS|0.000577151587166865__11179|SOD1|0.00227846138246539__ 0 0 0 0 0 19008 18370853 22362 20996 11179 SOD1 SOD1 SOD1 1 2.4 Mutant SOD1 likely induces selective vulnerability of motor neurons through a combination 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19009 18370853 22363 20996 11179 SOD1 SOD1 SOD1 16 2.4 by noxious signals originating from nonneuronal neighboring cells where mutant SOD1 induces an inflammatory response that accelerates disease progression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19144 18375019 22637 9905 5438 IFNG IFN IFN 10 1.1 astrocytes and U-373 MG cells were stimulated with interferon (IFN)-gamma IFN -gamma (150U/ml), 150U ml their supernatants significantly reduced SH-SY5Y cell 1 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.00127867678591803<>ScoreDetail__5438|IFNG|0.00101125079186787__5417|IFNA1|0.00127867678591803__ 0 0 0 0 0 19145 18375019 22639 9905 5438 IFNG IFN-gamma IFN-gamma 8 1.1 These combinations were also unable to enhance the IFN-gamma effect 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19146 18375019 22641 9905 5438 IFNG IFN-gamma IFN-gamma 11 1.1 result indicates that the neurotoxic effect was proceeding through the IFN-gamma receptor (IFNGR)-JAK-STAT IFNGR -JAK-STAT intracellular pathway 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19147 18375019 22641 9906 5439 IFNGR1 IFNGR IFNGR 13 1.6 the neurotoxic effect was proceeding through the IFN-gamma receptor (IFNGR)-JAK-STAT IFNGR -JAK-STAT intracellular pathway 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19148 18375019 22642 9906 5439 IFNGR1 IFNGR IFNGR 4 1.6 To establish that the IFNGR is expressed on both cultured astrocytes and U-373 MG cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19149 18375019 22642 9906 5439 IFNGR1 IFNGR IFNGR 26 1.6 performed RT-PCR on total RNA extracts to identify a specific IFNGR product 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19150 18375019 22643 9906 5439 IFNGR1 IFNGR IFNGR 15 1.6 on these cultured cells by immunocytochemistry using an antibody to IFNGR 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19151 18375019 22644 9906 5439 IFNGR1 IFNGR IFNGR 11 1.6 using human postmortem material we showed sharp upregulation of the IFNGR on activated astrocytes in affected areas in Alzheimer's disease Parkinson's 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19152 18375019 22645 9905 5438 IFNG IFN-gamma IFN-gamma 12 1.1 suggest that activated astrocytes may become neurotoxic when stimulated by IFN-gamma and may therefore exacerbate the pathology in a spectrum of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19222 18384649 22733 17031 9232 PPARA PPAR PPAR 0 2.2 PPAR a therapeutic target in Parkinson's disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19223 18384649 22737 17031 9232 PPARA PPAR PPAR 3 2.2 Peroxisome proliferator-activated receptor (PPAR), PPAR a member of nuclear receptor superfamily regulates development tissue differentiation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19224 18384649 22738 17031 9232 PPARA PPAR PPAR 2 2.2 Recently several PPAR agonists were shown to exert neuroprotective activity against oxidative damage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19225 18384649 22739 17031 9232 PPARA PPAR PPAR 4 2.2 Similarly regular intake of PPAR activating non-steroidal anti-inflammatory drugs such as indomethacin and ibuprofen was 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19226 18384649 22740 17031 9232 PPARA PPAR PPAR 12 2.2 article we review studies relating to the neuroprotective effect of PPAR agonists in in vitro and in vivo models of PD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19227 18384649 22741 17031 9232 PPARA PPAR PPAR 8 2.2 Similarly the pharmacological mechanism in neuroprotective actions of PPAR agonists is also reviewed 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 19228 18384649 22742 17031 9232 PPARA PPAR PPAR 2 2.2 In conclusion PPAR agonists exert neuroprotective actions by regulating the expression of a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20051 18397603 23527 4039 1774 CDK5 CDK5 CDK5 8 0.3 Local expression of mIgf-1 modulates ubiquitin caspase and CDK5 expression in skeletal muscle of an ALS mouse model 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20052 18397603 23527 20996 11179 SOD1 ALS ALS 15 0.5 ubiquitin caspase and CDK5 expression in skeletal muscle of an ALS mouse model 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00116148231049488<>ScoreDetail__5468|IGFALS|0.0005161100051611__11179|SOD1|0.00116148231049488__ 0 0 0 0 0 20053 18397603 23528 20996 11179 SOD1 ALS ALS 19 0.5 altered in several neuromuscular diseases including amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00116148231049488<>ScoreDetail__5468|IGFALS|0.0005161100051611__11179|SOD1|0.00116148231049488__ 0 0 0 0 0 20054 18397603 23530 20996 11179 SOD1 SOD SOD 29 0.8 the spinal cord and enhanced motor neuronal survival in SOD(G93A) SOD G93A mice delaying the onset and progression of the disease 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20055 18397603 23530 9939 5464 IGF1 IGF1 Igf-1 9 0.0 We previously reported that muscle-restricted expression of a localized Igf-1 isoform maintained muscle integrity stabilized neuromuscular junctions reduced inflammation in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20056 18397603 23533 20996 11179 SOD1 SOD SOD 12 0.8 Ubiquitin expression and caspase activity resulted markedly increased in SOD(G93A) SOD G93A muscle but maintained at very low levels in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20057 18397603 23533 20996 11179 SOD1 SOD SOD 22 0.8 muscle but maintained at very low levels in the SOD(G93A) SOD G93A x MLC/mIgf-1 MLC mIgf-1 (SOD(G93A)/mIgf-1) SOD G93A mIgf-1 transgenic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20058 18397603 23533 20996 11179 SOD1 SOD SOD 25 0.8 in the SOD(G93A) SOD G93A x MLC/mIgf-1 MLC mIgf-1 (SOD(G93A)/mIgf-1) SOD G93A mIgf-1 transgenic muscle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20059 18397603 23533 13284 17082 MLC1 MLC MLC 24 0.3 very low levels in the SOD(G93A) SOD G93A x MLC/mIgf-1 MLC mIgf-1 (SOD(G93A)/mIgf-1) SOD G93A mIgf-1 transgenic muscle 6 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>17082|MLC1|23209|Complete__29823|MYL6B|140465|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 20060 18397603 23534 4039 1774 CDK5 CDK5 CDK5 2 0.3 In addition CDK5 expression a serine-threonine protein kinase that has been implicated in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20061 18397603 23534 20996 11179 SOD1 SOD SOD 26 0.8 processes in nerve and muscle cells was reduced in SOD(G93A) SOD G93A muscle but increased in SOD(G93A)/mIgf-1 SOD G93A mIgf-1 muscle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20062 18397603 23534 20996 11179 SOD1 SOD SOD 31 0.8 reduced in SOD(G93A) SOD G93A muscle but increased in SOD(G93A)/mIgf-1 SOD G93A mIgf-1 muscle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20063 18397603 23535 5518 24594 DCTN5 p25 p25 4 0.8 Notably while the toxic p25 protein accumulated in SOD(G93A) SOD G93A muscle no accumulation was 1 JUMiner_v2.2 1 0 0 2 1775 TotalCon:3<>24594|DCTN5|84516|No_GeneRif__24164|TPPP|11076|Complete__1775|CDK5R1|8851|Complete__<>AvaiableGeneRif=2<>BEST:1775|CDK5R1|0.00131791552703081<>ScoreDetail__1775|CDK5R1|0.00131791552703081__24164|TPPP|0.000706364342727979__ 0 0 0 0 0 20064 18397603 23535 20996 11179 SOD1 SOD SOD 8 0.8 Notably while the toxic p25 protein accumulated in SOD(G93A) SOD G93A muscle no accumulation was evident in the SOD(G93A)/mIgf-1 SOD 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20065 18397603 23535 20996 11179 SOD1 SOD SOD 16 0.8 SOD G93A muscle no accumulation was evident in the SOD(G93A)/mIgf-1 SOD G93A mIgf-1 muscle 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 20066 18397603 23537 20996 11179 SOD1 ALS ALS 22 0.5 the attenuation of muscle wasting in the mouse model of ALS disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00116148231049488<>ScoreDetail__5468|IGFALS|0.0005161100051611__11179|SOD1|0.00116148231049488__ 0 0 0 0 0 9656 18414597 11013 22551 11892 TNF TNF-alpha TNF-alpha 2 1.5 Pro-inflammatory cytokines (TNF-alpha TNF-alpha and IL-1 secretory phospholipase A(2) A 2 IIA and lipoprotein-PLA(2) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9657 18414597 11013 10437 5992 IL1B IL-1 IL-1 4 1.0 Pro-inflammatory cytokines (TNF-alpha TNF-alpha and IL-1 secretory phospholipase A(2) A 2 IIA and lipoprotein-PLA(2) lipoprotein-PLA 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9658 18414597 11015 22551 11892 TNF TNF-alpha TNF-alpha 0 1.5 TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9659 18414597 11015 10437 5992 IL1B IL-1 IL-1 2 1.0 TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids ceramide and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9660 18414597 11020 14569 7897 NPC1 NPC1 NPC1 26 0.9 Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes resulting in defective cholesterol transport and cholesterol 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9661 18414597 11020 14571 14537 NPC2 NPC2 NPC2 28 1.4 C is due to mutations in either the NPC1 or NPC2 genes resulting in defective cholesterol transport and cholesterol accumulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9751 18422522 11247 14538 7876 NOS3 eNOS eNOS 25 2.2 contrast the biological significance of endothelial nitric oxide synthase (eNOS) eNOS overexpression that occurs in several pathological conditions has not yet 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9752 18422522 11248 622 443 ALS2 ALS2 ALS2 34 1.5 a protein causing an early-onset type of amyotrophic lateral sclerosis ALS2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9753 18422522 11249 14538 7876 NOS3 eNOS eNOS 3 2.2 We found that eNOS which is endogenously expressed by these cells was activated by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9754 18422522 11249 22551 11892 TNF TNF-alpha TNF-alpha 17 1.8 by these cells was activated by tumour necrosis factor-alpha (TNF-alpha), TNF-alpha a proinflammatory cytokine that plays important roles in ALS2 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9755 18422522 11249 622 443 ALS2 ALS2 ALS2 26 1.5 (TNF-alpha), TNF-alpha a proinflammatory cytokine that plays important roles in ALS2 and several neurodegenerative diseases 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9756 18422522 11250 22551 11892 TNF TNF-alpha TNF-alpha-dependent 1 1.8 The TNF-alpha-dependent eNOS activation occurred through generation by sphingosine-kinase-1 of sphingosine-1-phosphate stimulation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9757 18422522 11250 14538 7876 NOS3 eNOS eNOS 2 2.2 The TNF-alpha-dependent eNOS activation occurred through generation by sphingosine-kinase-1 of sphingosine-1-phosphate stimulation of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9758 18422522 11250 14538 7876 NOS3 eNOS eNOS 36 2.2 and dominant negative constructs specific for the enzymes and receptors eNOS activation by TNF-alpha conferred cytoprotection from excitotoxicity and neurotoxic cues 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9759 18422522 11250 22551 11892 TNF TNF-alpha TNF-alpha 39 1.8 constructs specific for the enzymes and receptors eNOS activation by TNF-alpha conferred cytoprotection from excitotoxicity and neurotoxic cues such as reactive 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 9760 18422522 11250 543 391 AKT1 AKT Akt 19 0.0 of sphingosine-1-phosphate stimulation of its membrane receptors and activation of Akt as determined using small interference RNA and dominant negative constructs 2 JUMiner_v2.2 1 1 akt; 0 0 0 0 0 0 0 0 9761 18422522 11251 14538 7876 NOS3 eNOS eNOS 6 2.2 Our results suggest that overexpression of eNOS by neurones is a broad-range protective mechanism activated during damage 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10356 18425621 11987 20996 11179 SOD1 ALS ALS 8 0.0 Objective Neuroinflammation contributes to motor neuron degeneration in ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000723351088314592<>ScoreDetail__5468|IGFALS|0.000723351088314592__11179|SOD1|0.000577648692549949__ 0 0 0 0 0 10357 18425621 11988 21921 11791 TCHH THL THL 1 0.0 Thalidomide (THL) THL shows potent anti-inflammatory properties and increased the lifespan in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10358 18425621 11988 20996 11179 SOD1 ALS ALS 11 0.0 THL shows potent anti-inflammatory properties and increased the lifespan in ALS transgenic mice 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000723351088314592<>ScoreDetail__5468|IGFALS|0.000723351088314592__11179|SOD1|0.000577648692549949__ 0 0 0 0 0 10359 18425621 11989 21921 11791 TCHH THL THL 19 0.0 treatment of ALS.We conducted a pilot randomized clinical trial of THL in patients with ALS to assess safety feasibility and preliminary 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10360 18425621 11989 20996 11179 SOD1 ALS ALS 23 0.0 a pilot randomized clinical trial of THL in patients with ALS to assess safety feasibility and preliminary estimates of treatment efficacy 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000723351088314592<>ScoreDetail__5468|IGFALS|0.000723351088314592__11179|SOD1|0.000577648692549949__ 0 0 0 0 0 10361 18425621 11990 21921 11791 TCHH THL THL 5 0.0 Methods Patients were randomized to THL in combination with riluzole (n n = 18 or riluzole 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10362 18425621 11991 21921 11791 TCHH THL THL 0 0.0 THL was initiated at 100 mg per day for 6 weeks 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10363 18425621 11993 21921 11791 TCHH THL THL 5 0.0 Results Within 12 weeks of THL treatment nine THL patients (50%) 50% developed bradycardia defined as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10364 18425621 11993 21921 11791 TCHH THL THL 8 0.0 Results Within 12 weeks of THL treatment nine THL patients (50%) 50% developed bradycardia defined as a heart rate 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10365 18425621 11994 21921 11791 TCHH THL THL 8 0.0 Mean heart rate dropped by 17 bpm with THL treatment 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10366 18425621 11999 21921 11791 TCHH THL THL 9 0.0 Conclusion Bradycardia was the most common adverse event of THL treatment in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10367 18425621 11999 20996 11179 SOD1 ALS ALS 12 0.0 was the most common adverse event of THL treatment in ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000723351088314592<>ScoreDetail__5468|IGFALS|0.000723351088314592__11179|SOD1|0.000577648692549949__ 0 0 0 0 0 10368 18425621 12000 21921 11791 TCHH THL THL-related 0 0.0 THL-related bradycardia does not appear to be ALS-specific 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10369 18425621 12000 20996 11179 SOD1 ALS ALS-specific 7 0.0 THL-related bradycardia does not appear to be ALS-specific 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000723351088314592<>ScoreDetail__5468|IGFALS|0.000723351088314592__11179|SOD1|0.000577648692549949__ 0 0 0 0 0 10370 18425621 12001 21921 11791 TCHH THL THL-induced 11 0.0 is conceivable however that the unexpected frequency and severity of THL-induced bradycardia may be related to subclinical involvement of the autonomic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10371 18425621 12001 20996 11179 SOD1 ALS ALS 25 0.0 related to subclinical involvement of the autonomic nervous system in ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000723351088314592<>ScoreDetail__5468|IGFALS|0.000723351088314592__11179|SOD1|0.000577648692549949__ 0 0 0 0 0 10372 18425621 12002 21921 11791 TCHH THL THL 11 0.0 cardiac toxicity discourages further clinical trials and compassionate use of THL in ALS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10373 18425621 12002 20996 11179 SOD1 ALS ALS 13 0.0 discourages further clinical trials and compassionate use of THL in ALS 1 JUMiner_v2.2 1 0 0 2 5468 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:5468|IGFALS|0.000723351088314592<>ScoreDetail__5468|IGFALS|0.000723351088314592__11179|SOD1|0.000577648692549949__ 0 0 0 0 0 10983 18436268 12688 20996 11179 SOD1 ALS ALS 3 2.4 Amyotrophic lateral sclerosis (ALS) ALS is a neurodegenerative disease caused by selective degeneration of motor 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 10984 18436268 12689 20996 11179 SOD1 SOD1 SOD1 5 3.4 Mutations in copper/zinc copper zinc superoxide dismutase (SOD1) SOD1 account for 20% cases of familial ALS (fALS), fALS but 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10985 18436268 12689 20996 11179 SOD1 ALS ALS 12 2.4 superoxide dismutase (SOD1) SOD1 account for 20% cases of familial ALS (fALS), fALS but the underlying pathogenetic mechanisms are largely unknown 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 10986 18436268 12690 20996 11179 SOD1 SOD1 SOD1 1 3.4 Using SOD1 G93A mice model of ALS we demonstrated that mutation in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10987 18436268 12690 20996 11179 SOD1 ALS ALS 6 2.4 Using SOD1 G93A mice model of ALS we demonstrated that mutation in SOD1 caused a significant increase 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 10988 18436268 12690 20996 11179 SOD1 SOD1 SOD1 12 3.4 G93A mice model of ALS we demonstrated that mutation in SOD1 caused a significant increase in the level of plasma homocysteine 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10989 18436268 12691 20996 11179 SOD1 SOD1 SOD1 38 3.4 assess the neuroprotective effect of FA and B12 in the SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10990 18436268 12693 14535 7873 NOS2A iNOS iNOS 32 2.5 and inhibited the expression of inducible nitric oxide synthase (iNOS) iNOS and tumor necrosis factor-alpha (TNF-_amp_#x3b1;) TNF-_amp_#x3b1 in spinal cord 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10991 18436268 12693 22551 11892 TNF TNF TNF-A 37 1.2 nitric oxide synthase (iNOS) iNOS and tumor necrosis factor-alpha (TNF-_amp_#x3b1;) TNF-_amp_#x3b1 in spinal cord 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10992 18436268 12694 16068 270 PARP1 PARP PARP 15 1.9 levels of cleaved caspase-3 and poly(ADP-ribose)polymerase poly ADP-ribose polymerase (PARP) PARP but up-regulated the level of anti-apoptotic protein Bcl-2 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000860606472625916<>ScoreDetail__2187|COL11A2|0.000418935902806871__270|PARP1|0.000860606472625916__ 0 0 0 0 0 10993 18436268 12694 1576 990 BCL2 Bcl-2 Bcl-2 23 3.2 polymerase (PARP) PARP but up-regulated the level of anti-apoptotic protein Bcl-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10994 18436268 12694 24185 29175 WDTC1 ADP ADP-ribose 14 0.2 treatment decreased the levels of cleaved caspase-3 and poly(ADP-ribose)polymerase poly ADP-ribose polymerase (PARP) PARP but up-regulated the level of anti-apoptotic protein 5 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 10995 18436268 12699 20996 11179 SOD1 ALS ALS 3 2.4 Amyotrophic lateral sclerosis (ALS) ALS is the most frequently diagnosed form of adult-onset motor neuron 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 10996 18436268 12700 20996 11179 SOD1 ALS ALS 0 2.4 ALS is characterized by the selective degeneration of lower and upper 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 10997 18436268 12701 20996 11179 SOD1 ALS ALS 4 2.4 Around 10% cases of ALS patients are autosomal dominant referred as fALS and 20% patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 10998 18436268 12701 20996 11179 SOD1 SOD1 SOD1 28 3.4 the gene encoding for Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 ( Al-Chalabi and Leigh 2000 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 10999 18436268 12702 20996 11179 SOD1 SOD1 SOD1 3 3.4 Over-expression of mutant SOD1 gene in mice causes a progressive motor neuron disease resembling 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11000 18436268 12702 20996 11179 SOD1 ALS ALS 21 2.4 neuron disease resembling the most clinical features of the human ALS which make them suitable for studying the pathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11001 18436268 12702 20996 11179 SOD1 ALS ALS 31 2.4 ALS which make them suitable for studying the pathogenesis of ALS ( Gurney et_amp_#xa0 al. 1994 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11002 18436268 12703 20996 11179 SOD1 SOD1 SOD1 5 3.4 In this study we used SOD1 G93A mice model to study the association of homocysteine (Hcy) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11003 18436268 12703 20996 11179 SOD1 ALS ALS 20 2.4 the association of homocysteine (Hcy) Hcy and the development of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11004 18436268 12707 20996 11179 SOD1 SOD1 SOD1 14 3.4 that Hcy-immunoreactive astrocytes presented in the spinal cord of symptomatic SOD1 G93A mice and Hcy even at the physiological concentration induced 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11005 18436268 12707 20996 11179 SOD1 SOD1 SOD1 33 3.4 concentration induced significant cytotoxicity in neuronal cell-line transfected with mutant SOD1 gene suggesting Hcy may play an important role in the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11006 18436268 12707 20996 11179 SOD1 ALS ALS 46 2.4 Hcy may play an important role in the pathogenesis of ALS ( Chung et_amp_#xa0 al. 2003 and Sung et_amp_#xa0 al. 2002 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11007 18436268 12708 22551 11892 TNF TNF TNF-A 14 1.2 of Hcy increased the expression of inflammatory factors such as TNF-_amp_#x3b1 and promoted reactive oxygen species (ROS) ROS as well as 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11008 18436268 12708 18723 10261 ROS1 ROS ROS 20 0.0 factors such as TNF-_amp_#x3b1 and promoted reactive oxygen species (ROS) ROS as well as activated NMDA subtype of the glutamate receptors 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11009 18436268 12709 20996 11179 SOD1 ALS ALS 15 2.4 hypothesize that Hcy may be involved in the pathogenesis of ALS and lowering Hcy may be beneficial to this disease 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11010 18436268 12715 20996 11179 SOD1 SOD1 SOD1 25 3.4 can lower the Hcy level and provide the neuroprotection in SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11011 18436268 12716 20996 11179 SOD1 ALS ALS 24 2.4 and B12 treatment has clinical value for the treatment of ALS patients in the future 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11012 18436268 12722 20996 11179 SOD1 SOD1 SOD1 5 3.4 The colony of well-characterized TgN (SOD1 SOD1 G93A Gur transgenic males which resemble most clinical features of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11013 18436268 12722 22055 11764 TG TGN TgN 4 0.2 The colony of well-characterized TgN (SOD1 SOD1 G93A Gur transgenic males which resemble most clinical 5 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 11014 18436268 12726 20996 11179 SOD1 SOD1 SOD1 1 3.4 The SOD1 G93A mice ( n = 48 were randomized divided into 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11015 18436268 12726 20996 11179 SOD1 SOD1 SOD1 20 3.4 four groups (1) 1 orally administrated vehicle 0.9% saline (SOD1 SOD1 group n = 12 (2) 2 orally administrated 4 mg 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11016 18436268 12728 20996 11179 SOD1 SOD1 SOD1 5 3.4 Among them 36 transgenic mice (SOD1 SOD1 group n = 9 FA-SOD1 group n = 9 B12-SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11017 18436268 12730 20996 11179 SOD1 SOD1 SOD1 12 3.4 10 of the wild-type littermates at the same age as SOD1 G93A mice were used as controls for the histopathological staining 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11018 18436268 12741 20996 11179 SOD1 SOD1 SOD1 6 3.4 The initial sign of disease in SOD1 G93A mice is resting tremor and progressive development of gait 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11019 18436268 12759 19728 9075 SERPINF2 API API 9 0.0 MS/MS MS MS system was a triple quadrupole mass spectrometer API 3000 instrument (ABI-SCIEX, ABI-SCIEX Toronto Canada equipped with Turbo Ionspray 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11020 18436268 12766 20996 11179 SOD1 SOD1 SOD1 0 3.4 SOD1 G93A mice (SOD1 SOD1 group n = 3 FA-SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11021 18436268 12766 20996 11179 SOD1 SOD1 SOD1 3 3.4 SOD1 G93A mice (SOD1 SOD1 group n = 3 FA-SOD1 mice n = 3 B12-SOD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11022 18436268 12779 8254 4235 GFAP GFAP GFAP 10 2.5 used the primary antibody of glial fibrillary acidic protein (GFAP, GFAP 1 2000 Sigma St Louis MO USA and CD11b (1:100, 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11023 18436268 12779 10731 6149 ITGAM CD11b CD11b 18 1.0 (GFAP, GFAP 1 2000 Sigma St Louis MO USA and CD11b (1:100, 1 100 Serotec Oxford UK to examine the activation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11024 18436268 12788 14535 7873 NOS2A iNOS iNOS 23 2.5 0.45 _amp_#x3bc m PVDF membrane incubated with primary antibodies of iNOS (1:5000, 1 5000 Chemicon CA USA TNF-_amp_#x3b1 (1:1000, 1 1000 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11025 18436268 12788 22551 11892 TNF TNF TNF-A 28 1.2 primary antibodies of iNOS (1:5000, 1 5000 Chemicon CA USA TNF-_amp_#x3b1 (1:1000, 1 1000 Cell signaling MA USA Bcl-2 (1:1000, 1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11026 18436268 12788 1576 990 BCL2 Bcl-2 Bcl-2 34 3.2 CA USA TNF-_amp_#x3b1 (1:1000, 1 1000 Cell signaling MA USA Bcl-2 (1:1000, 1 1000 Santa Cruz Biotechnology Inc. Santa Cruz cleaved 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11027 18436268 12788 16068 270 PARP1 PARP PARP 49 1.9 Cruz cleaved caspase-3 (1:1000, 1 1000 Cell signaling MA USA PARP and cleavage (1:1000, 1 1000 Cell signaling MA USA respectively 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000860606472625916<>ScoreDetail__2187|COL11A2|0.000418935902806871__270|PARP1|0.000860606472625916__ 0 0 0 0 0 11028 18436268 12788 19573 10691 SDS SDS SDS 10 0.0 40 _amp_#x3bc g of each sample was separated in 8% SDS gel transferred onto 0.45 _amp_#x3bc m PVDF membrane incubated with 1 JUMiner_v2.2 1 0 0 2 10691 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:10691|SDS|0.000488963397597094<>ScoreDetail__10691|SDS|0.000488963397597094__19440|SBDS|0.000312857868080233__ 0 0 0 0 0 11029 18436268 12789 3778 10620 CCL21 ECL ECL 35 0.0 Pierce IL USA and then protein bands were visualized using ECL (Pierce, Pierce IL USA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11030 18436268 12790 211 132 ACTB beta-actin beta-actin 8 0.3 Afterwards the blots were stripped and stained with beta-actin antibody (1:4000, 1 4000 Cell signaling MA USA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11031 18436268 12800 20996 11179 SOD1 SOD1 SOD1 13 3.4 and B12 on the onset of symptoms and lifespan in SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11032 18436268 12801 20996 11179 SOD1 SOD1 SOD1 14 3.4 or B12 treatment can influence the onset of symptoms in SOD1 G93A mice we analyzed the motor function of all animals 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11033 18436268 12802 20996 11179 SOD1 SOD1 SOD1 0 3.4 SOD1 G93A mice usually recapitulated the clinical progression of ALS by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11034 18436268 12802 20996 11179 SOD1 ALS ALS 9 2.4 SOD1 G93A mice usually recapitulated the clinical progression of ALS by displaying overt hind-limb disability at the age about 100 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11035 18436268 12803 20996 11179 SOD1 SOD1 SOD1 25 3.4 of the onset of symptoms compared with the mice in SOD1 group (114.4 114.4 _amp_#xb1 1.7 116.3 _amp_#xb1 2.0 vs 107.9 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11036 18436268 12805 20996 11179 SOD1 SOD1 SOD1 8 3.4 In addition FA or FA B12 treated SOD1 G93A mice had significant 9-day and 13-day extension in lifespan 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11037 18436268 12805 20996 11179 SOD1 SOD1 SOD1 21 3.4 had significant 9-day and 13-day extension in lifespan compared with SOD1 group mice respectively (137.7 137.7 _amp_#xb1 1.9 141.4 _amp_#xb1 2.9 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11038 18436268 12806 20996 11179 SOD1 SOD1 SOD1 9 3.4 There was no significant difference between B12-SOD1 group and SOD1 group in the lifespan (132.3 132.3 _amp_#xb1 1.9 vs 128.8 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11039 18436268 12809 20996 11179 SOD1 SOD1 SOD1 11 3.4 was performed to examine the total plasma Hcy level in SOD1 G93A and wild-type litter mate mice at the age of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11040 18436268 12810 20996 11179 SOD1 SOD1 SOD1 5 3.4 The level of Hcy in SOD1 group was 180% of the level in wild-type mice (6.84 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11041 18436268 12810 20996 11179 SOD1 SOD1 SOD1 55 3.4 0.67 vs 6.84 _amp_#xb1 0.4 _amp_#x3bc;mol/L _amp_#x3bc mol L in SOD1 group mice ( Fig._amp_#xa0 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11042 18436268 12811 20996 11179 SOD1 SOD1 SOD1 24 3.4 L vs 6.84 _amp_#xb1 0.4 _amp_#x3bc;mol/L _amp_#x3bc mol L in SOD1 group mice ( Fig._amp_#xa0 2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11043 18436268 12812 20996 11179 SOD1 SOD1 SOD1 25 3.4 alone could significantly reduce the level of Hcy in the SOD1 G93A transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11044 18436268 12816 20996 11179 SOD1 SOD1 SOD1 1 3.4 In SOD1 group mice at the age of 120 days there were 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11045 18436268 12817 20996 11179 SOD1 SOD1 SOD1 19 3.4 were 74.5% and 88.3% more motor neurons than mice in SOD1 group (383.5 383.5 _amp_#xb1 24.43 413.67 _amp_#xb1 32.48 vs 219.67 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11046 18436268 12822 20996 11179 SOD1 ALS ALS 9 2.4 Inflammation plays an important role in the pathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11047 18436268 12824 8254 4235 GFAP GFAP GFAP 5 2.5 In our study we used GFAP and CD11b to examine the status of microglia and astrocyte 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11048 18436268 12824 10731 6149 ITGAM CD11b CD11b 7 1.0 In our study we used GFAP and CD11b to examine the status of microglia and astrocyte respectively in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11049 18436268 12824 20996 11179 SOD1 SOD1 SOD1 23 3.4 microglia and astrocyte respectively in the spinal cord sections of SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11050 18436268 12825 20996 11179 SOD1 SOD1 SOD1 12 3.4 overwhelming microglial and astrocytic activation in the spinal cord of SOD1 G93A mice at the age of 120 days whereas the_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11051 18436268 12826 20996 11179 SOD1 SOD1 SOD1 18 3.4 activation between the mice treated with B12 alone and control SOD1 G93A mice ( Fig._amp_#xa0 4 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11052 18436268 12827 14535 7873 NOS2A iNOS iNOS 15 2.5 significant increase in the_amp_#xa0 expression of inflammation-related factors such as iNOS and TNF-_amp_#x3b1 in SOD1 G93A transgenic mice ( Almer et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11053 18436268 12827 22551 11892 TNF TNF TNF-A 17 1.2 in the_amp_#xa0 expression of inflammation-related factors such as iNOS and TNF-_amp_#x3b1 in SOD1 G93A transgenic mice ( Almer et_amp_#xa0 al. 1999 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11054 18436268 12827 20996 11179 SOD1 SOD1 SOD1 19 3.4 expression of inflammation-related factors such as iNOS and TNF-_amp_#x3b1 in SOD1 G93A transgenic mice ( Almer et_amp_#xa0 al. 1999 Hensley et_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11055 18436268 12828 14535 7873 NOS2A iNOS iNOS 10 2.5 Therefore in our study we examined the protein levels of iNOS and TNF-_amp_#x3b1 in the spinal cord of the mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11056 18436268 12828 22551 11892 TNF TNF TNF-A 12 1.2 our study we examined the protein levels of iNOS and TNF-_amp_#x3b1 in the spinal cord of the mice 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11057 18436268 12829 14535 7873 NOS2A iNOS iNOS 4 2.5 We_amp_#xa0 observed significant reduction of iNOS and TNF-_amp_#x3b1 in FA-SOD1 group or FA SOD1 group mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11058 18436268 12829 22551 11892 TNF TNF TNF-A 6 1.2 We_amp_#xa0 observed significant reduction of iNOS and TNF-_amp_#x3b1 in FA-SOD1 group or FA SOD1 group mice compared with 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11059 18436268 12829 20996 11179 SOD1 SOD1 SOD1 13 3.4 reduction of iNOS and TNF-_amp_#x3b1 in FA-SOD1 group or FA SOD1 group mice compared with mice in SOD1 group ( Fig._amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11060 18436268 12829 20996 11179 SOD1 SOD1 SOD1 20 3.4 group or FA SOD1 group mice compared with mice in SOD1 group ( Fig._amp_#xa0 5 A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11061 18436268 12830 14535 7873 NOS2A iNOS iNOS 15 2.5 FA B12 was more effective in lowing the level of iNOS ( Fig._amp_#xa0 5 C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11062 18436268 12831 20996 11179 SOD1 SOD1 SOD1 12 3.4 results documented that the inflammation in FA-SOD1 group or FA SOD1 group was strongly suppressed compared with SOD1 group 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11063 18436268 12831 20996 11179 SOD1 SOD1 SOD1 19 3.4 group or FA SOD1 group was strongly suppressed compared with SOD1 group 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11064 18436268 12835 20996 11179 SOD1 SOD1 SOD1 14 3.4 drugs FA and B12 had the anti-apoptotic effects in the SOD1 G93A transgenic mice we determined the protein level of Bcl-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11065 18436268 12835 1576 990 BCL2 Bcl-2 Bcl-2 24 3.2 SOD1 G93A transgenic mice we determined the protein level of Bcl-2 cleaved caspase-3 and PARP in the spinal cord after FA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11066 18436268 12835 16068 270 PARP1 PARP PARP 28 1.9 we determined the protein level of Bcl-2 cleaved caspase-3 and PARP in the spinal cord after FA B12 or FA B12 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000860606472625916<>ScoreDetail__2187|COL11A2|0.000418935902806871__270|PARP1|0.000860606472625916__ 0 0 0 0 0 11067 18436268 12836 1576 990 BCL2 Bcl-2 Bcl-2 14 3.2 FA or FA B12 treatment can increase the level of Bcl-2 and reduce the level of cleaved caspase-3 and cleaved PARP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11068 18436268 12836 16068 270 PARP1 PARP PARP 24 1.9 Bcl-2 and reduce the level of cleaved caspase-3 and cleaved PARP ( Fig._amp_#xa0 5 B 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000860606472625916<>ScoreDetail__2187|COL11A2|0.000418935902806871__270|PARP1|0.000860606472625916__ 0 0 0 0 0 11069 18436268 12837 1576 990 BCL2 Bcl-2 Bcl-2 12 3.2 we found FA B12 treatment can elevate the level of Bcl-2 in SOD1 G93A mice up to the level of wild-type 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11070 18436268 12837 20996 11179 SOD1 SOD1 SOD1 14 3.4 FA B12 treatment can elevate the level of Bcl-2 in SOD1 G93A mice up to the level of wild-type which could 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11071 18436268 12837 20996 11179 SOD1 SOD1 SOD1 37 3.4 that FA B12 is effective in suppressing apoptosis in the SOD1 mice model 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11072 18436268 12842 20996 11179 SOD1 ALS ALS 29 2.4 prolong the lifespan by protecting motor neurons against apoptosis in ALS transgenic mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11073 18436268 12843 20996 11179 SOD1 ALS ALS 11 2.4 The neuroprotective effects of FA or FA B12 treatment in ALS transgenic model may be related to their biological role in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11074 18436268 12843 20996 11179 SOD1 SOD1 SOD1 40 3.4 B12 treatment significantly attenuates the increased level of Hcy in SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11075 18436268 12844 14535 7873 NOS2A iNOS iNOS 20 2.5 treatment can suppress the production of inflammatory factors such as iNOS and TNF-_amp_#x3b1 and inhibit the activation of microglia and astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11076 18436268 12844 22551 11892 TNF TNF TNF-A 22 1.2 suppress the production of inflammatory factors such as iNOS and TNF-_amp_#x3b1 and inhibit the activation of microglia and astrocytes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11077 18436268 12845 1576 990 BCL2 Bcl-2 Bcl-2 16 3.2 or FA B12 treatment has significant anti-apoptotic effects by increasing Bcl-2 expression and inhibiting cleaved caspase-3 and cleaved PARP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11078 18436268 12845 16068 270 PARP1 PARP PARP 24 1.9 by increasing Bcl-2 expression and inhibiting cleaved caspase-3 and cleaved PARP 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000860606472625916<>ScoreDetail__2187|COL11A2|0.000418935902806871__270|PARP1|0.000860606472625916__ 0 0 0 0 0 11079 18436268 12846 20996 11179 SOD1 ALS ALS 13 2.4 have showed that there might be association between Hcy and ALS the role of Hcy in ALS development is not well 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11080 18436268 12846 20996 11179 SOD1 ALS ALS 19 2.4 association between Hcy and ALS the role of Hcy in ALS development is not well defined 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11081 18436268 12847 20996 11179 SOD1 ALS ALS 21 2.4 level of cytokine which may contribute to the progression of ALS ( Holven et_amp_#xa0 al. 2006 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11082 18436268 12848 22551 11892 TNF TNF TNF-A 13 1.2 that Hcy can enhance pro-inflammatory cytokines production such as interleukin-6 TNF-_amp_#x3b1 and C-reactive protein ( Holven et_amp_#xa0 al. 2006 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11083 18436268 12850 22551 11892 TNF TNF TNF-A 9 1.2 (2007) 2007 reported that Hcy could increase the expression of TNF-_amp_#x3b1 which plays a critical role in inflammatory responses and apoptosis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11084 18436268 12851 22551 11892 TNF TNF TNF-A 1 1.2 Furthermore TNF-_amp_#x3b1 can switch resting murine astrocytes to active state and up-regulate 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11085 18436268 12851 14535 7873 NOS2A iNOS iNOS 12 2.5 can switch resting murine astrocytes to active state and up-regulate iNOS expression and subsequently release nitric oxide ( Falsig et_amp_#xa0 al. 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11086 18436268 12852 14535 7873 NOS2A iNOS iNOS 9 2.5 In addition it was reported that the expression of iNOS was increased in the spinal cord of the SOD1 G93A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11087 18436268 12852 20996 11179 SOD1 SOD1 SOD1 18 3.4 of iNOS was increased in the spinal cord of the SOD1 G93A transgenic mice and activated microglia and astrocytes increased the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11088 18436268 12852 14535 7873 NOS2A iNOS iNOS 31 2.5 mice and activated microglia and astrocytes increased the production of iNOS which suggest that iNOS may contribute to the pathology of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11089 18436268 12852 14535 7873 NOS2A iNOS iNOS 35 2.5 and astrocytes increased the production of iNOS which suggest that iNOS may contribute to the pathology of ALS and represent a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11090 18436268 12852 20996 11179 SOD1 ALS ALS 42 2.4 which suggest that iNOS may contribute to the pathology of ALS and represent a valuable therapeutic target for the disease ( 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11091 18436268 12853 14535 7873 NOS2A iNOS iNOS 28 2.5 suppressed the glial activation as well as the expression of iNOS and TNF-_amp_#x3b1 in the spinal cord of SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11092 18436268 12853 22551 11892 TNF TNF TNF-A 30 1.2 glial activation as well as the expression of iNOS and TNF-_amp_#x3b1 in the spinal cord of SOD1 G93A mice at the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11093 18436268 12853 20996 11179 SOD1 SOD1 SOD1 36 3.4 expression of iNOS and TNF-_amp_#x3b1 in the spinal cord of SOD1 G93A mice at the age of 120 days 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11094 18436268 12854 20996 11179 SOD1 SOD1 SOD1 16 3.4 Hcy may play a role in the increased inflammation of SOD1 G93A mice model and lowering the level of Hcy by 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11095 18436268 12855 20996 11179 SOD1 ALS ALS 12 2.4 supports that the eventual process of motor neuron death in ALS may result from the activation of apoptotic pathways especially the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11096 18436268 12856 1576 990 BCL2 Bcl-2 Bcl-2 14 3.2 by regulating the expression of several important proteins such as Bcl-2 cleaved caspase-3 and cleaved PARP ( Baydas et_amp_#xa0 al. 2005 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11097 18436268 12856 16068 270 PARP1 PARP PARP 19 1.9 several important proteins such as Bcl-2 cleaved caspase-3 and cleaved PARP ( Baydas et_amp_#xa0 al. 2005 and Kruman et_amp_#xa0 al. 2000 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000860606472625916<>ScoreDetail__2187|COL11A2|0.000418935902806871__270|PARP1|0.000860606472625916__ 0 0 0 0 0 11098 18436268 12857 1576 990 BCL2 Bcl-2 Bcl-2 0 3.2 Bcl-2 plays a prominent role in ALS pathogenesis which is involved 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11099 18436268 12857 20996 11179 SOD1 ALS ALS 6 2.4 Bcl-2 plays a prominent role in ALS pathogenesis which is involved in the oxidative stress and in 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11100 18436268 12858 1576 990 BCL2 Bcl-2 Bcl-2 0 3.2 Bcl-2 family is implicated in the regulation of motor neuron death 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11101 18436268 12858 20996 11179 SOD1 SOD1 SOD1 12 3.4 is implicated in the regulation of motor neuron death in SOD1 G93A transgenic mice model and over-expression of Bcl-2 can significantly 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11102 18436268 12858 1576 990 BCL2 Bcl-2 Bcl-2 20 3.2 death in SOD1 G93A transgenic mice model and over-expression of Bcl-2 can significantly protect motor neurons in SOD1 G93A mice ( 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11103 18436268 12858 20996 11179 SOD1 SOD1 SOD1 27 3.4 and over-expression of Bcl-2 can significantly protect motor neurons in SOD1 G93A mice ( Kostic et_amp_#xa0 al. 1997 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11104 18436268 12859 1576 990 BCL2 Bcl-2 Bcl-2 17 3.2 FA or FA B12 treatment can increase the expression of Bcl-2 which provided an evidence for the neuroprotective effect of FA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11105 18436268 12859 20996 11179 SOD1 SOD1 SOD1 34 3.4 the neuroprotective effect of FA or FA B12 treatment in SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11106 18436268 12860 16068 270 PARP1 PARP PARP 4 1.9 Cleaved caspase-3 and cleaved PARP represent the downstream signals of apoptosis which may contribute to 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000860606472625916<>ScoreDetail__2187|COL11A2|0.000418935902806871__270|PARP1|0.000860606472625916__ 0 0 0 0 0 11107 18436268 12860 20996 11179 SOD1 SOD1 SOD1 20 3.4 apoptosis which may contribute to the motor neuron death in SOD1 G93A mice ( Pasinelli et al. 2000 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11108 18436268 12861 9653 5215 HSD17B7 PRAP PRAP 7 1.0 In addition reactive astrocytes could express cleaved PRAP in the central nervous system in SOD1 G93A mice ( 1 JUMiner_v2.2 1 0 0 2 5215 TotalCon:2<>5215|HSD17B7|51478|Complete__15687|SKAP2|8935|Complete__<>AvaiableGeneRif=2<>BEST:5215|HSD17B7|0.000311339959286313<>ScoreDetail__15687|SKAP2|0.000295527328218024__5215|HSD17B7|0.000311339959286313__ 0 0 0 0 0 11109 18436268 12861 20996 11179 SOD1 SOD1 SOD1 14 3.4 could express cleaved PRAP in the central nervous system in SOD1 G93A mice ( Chung et al. 2004 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11110 18436268 12863 9653 5215 HSD17B7 PRAP PRAP 15 1.0 induce apoptosis in neuronal cells resulting from the activation of PRAP 1 JUMiner_v2.2 1 0 0 2 5215 TotalCon:2<>5215|HSD17B7|51478|Complete__15687|SKAP2|8935|Complete__<>AvaiableGeneRif=2<>BEST:5215|HSD17B7|0.000311339959286313<>ScoreDetail__15687|SKAP2|0.000295527328218024__5215|HSD17B7|0.000311339959286313__ 0 0 0 0 0 11111 18436268 12864 1576 990 BCL2 Bcl-2 Bcl-2 17 3.2 FA B12 treatment could up-regulate the expression of anti-apoptotic protein Bcl-2 as well as down-regulated the expression of apoptosis-related proteins such 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11112 18436268 12864 16068 270 PARP1 PARP PARP 33 1.9 expression of apoptosis-related proteins such as cleaved caspase-3 and cleaved PARP 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000860606472625916<>ScoreDetail__2187|COL11A2|0.000418935902806871__270|PARP1|0.000860606472625916__ 0 0 0 0 0 11113 18436268 12865 20996 11179 SOD1 ALS ALS 28 2.4 FA or FA B12 could provide anti-apoptotic effect in the ALS transgenic mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11114 18436268 12866 20996 11179 SOD1 SOD1 SOD1 19 3.4 in the level of Hcy inflammation and apoptosis in the SOD1 G93A transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11115 18436268 12867 20996 11179 SOD1 SOD1 SOD1 51 3.4 a result inflammation and apoptosis remain high in B12 treated SOD1 G93A transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11116 18436268 12868 20996 11179 SOD1 ALS ALS 29 2.4 lifespan accompanied by the attenuation of motor neuron loss in ALS transgenic mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11117 18436268 12869 14535 7873 NOS2A iNOS iNOS 17 2.5 FA B12 possessed anti-inflammatory effects through inhibiting the expression of iNOS and TNF-_amp_#x3b1 and suppressing the activation of microglia and astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11118 18436268 12869 22551 11892 TNF TNF TNF-A 19 1.2 possessed anti-inflammatory effects through inhibiting the expression of iNOS and TNF-_amp_#x3b1 and suppressing the activation of microglia and astrocytes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11119 18436268 12870 16068 270 PARP1 PARP PARP 20 1.9 can significantly inhibit the levels of cleaved caspase-3 and cleaved PARP as well as up-regulate the levels of Bcl-2 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000860606472625916<>ScoreDetail__2187|COL11A2|0.000418935902806871__270|PARP1|0.000860606472625916__ 0 0 0 0 0 11120 18436268 12870 1576 990 BCL2 Bcl-2 Bcl-2 28 3.2 and cleaved PARP as well as up-regulate the levels of Bcl-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11121 18436268 12871 20996 11179 SOD1 ALS ALS 17 2.4 potential of FA or FA B12 for the treatment of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00180359344307603<>ScoreDetail__5468|IGFALS|0.000929775250879012__11179|SOD1|0.00180359344307603__ 0 0 0 0 0 11122 18436268 12872 20996 11179 SOD1 SOD1 SOD1 13 3.4 and B12 on the disease onset and the lifespan of SOD1 G93A mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11123 18436268 12873 20996 11179 SOD1 SOD1 SOD1 23 3.4 A and the probability of survival (B) B in the SOD1 group B12-SOD1 group FA-SOD1 group and FA B12-SOD1 group * 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11124 18436268 12876 20996 11179 SOD1 SOD1 SOD1 8 3.4 Data showed that the level of Hcy in SOD1 group was increased as compared with the wild-type mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11125 18436268 12877 20996 11179 SOD1 SOD1 SOD1 16 3.4 FA B12-SOD1 group mice was significantly decreased as compared with SOD1 group mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11126 18436268 12879 20996 11179 SOD1 SOD1 SOD1 30 3.4 group # P _amp_#x3c 0.01 (when when compared with the SOD1 group * N in each group = 8 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11127 18436268 12882 20996 11179 SOD1 SOD1 SOD1 4 3.4 (a) a Wild-type group (b) b SOD1 group (c) c B12-SOD1 group (d) d FA-SOD1 group (e) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11128 18436268 12884 20996 11179 SOD1 SOD1 SOD1 29 3.4 group # P _amp_#x3c 0.01 (when when compared with the SOD1 group * N in each group = 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11129 18436268 12887 10731 6149 ITGAM CD11b CD11b 0 1.0 CD11b and GFAP were used as the markers of microglia (red) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11130 18436268 12887 8254 4235 GFAP GFAP GFAP 2 2.5 CD11b and GFAP were used as the markers of microglia (red) red and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11131 18436268 12888 20996 11179 SOD1 SOD1 SOD1 26 3.4 in FA-SOD1 or FA B12-SOD1 group mice as compared with SOD1 group mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11132 18436268 12889 20996 11179 SOD1 SOD1 SOD1 10 3.4 While there was no difference between B12-SOD1 group mice and SOD1 group mice * N in each group = 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11133 18436268 12892 14535 7873 NOS2A iNOS iNOS 4 2.5 (A) A Western blot of iNOS and TNF-_amp_#x3b1 from spinal cord samples of G93A transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11134 18436268 12892 22551 11892 TNF TNF TNF-A 6 1.2 (A) A Western blot of iNOS and TNF-_amp_#x3b1 from spinal cord samples of G93A transgenic mice in five 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11135 18436268 12892 20996 11179 SOD1 SOD1 SOD1 21 3.4 G93A transgenic mice in five groups (WT: WT wild-type group SOD1 SOD1 group B12 B12-SOD1 group FA FA-SOD1 group FA B12 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11136 18436268 12892 20996 11179 SOD1 SOD1 SOD1 22 3.4 transgenic mice in five groups (WT: WT wild-type group SOD1 SOD1 group B12 B12-SOD1 group FA FA-SOD1 group FA B12 FA 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11137 18436268 12893 1576 990 BCL2 Bcl-2 Bcl-2 4 3.2 (B) B Western blot of Bcl-2 cleaved caspase-3 and cleaved PARP from spinal cord samples 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11138 18436268 12893 16068 270 PARP1 PARP PARP 9 1.9 (B) B Western blot of Bcl-2 cleaved caspase-3 and cleaved PARP from spinal cord samples 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000860606472625916<>ScoreDetail__2187|COL11A2|0.000418935902806871__270|PARP1|0.000860606472625916__ 0 0 0 0 0 11139 18436268 12894 14535 7873 NOS2A iNOS iNOS 7 2.5 (C_amp_#x2013;G) C_amp_#x2013 G Quantitative data of the expression of iNOS TNF-_amp_#x3b1 Bcl-2 cleaved caspase-3 and cleaved PARP in five groups 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11140 18436268 12894 22551 11892 TNF TNF TNF-A 8 1.2 (C_amp_#x2013;G) C_amp_#x2013 G Quantitative data of the expression of iNOS TNF-_amp_#x3b1 Bcl-2 cleaved caspase-3 and cleaved PARP in five groups 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11141 18436268 12894 1576 990 BCL2 Bcl-2 Bcl-2 9 3.2 C_amp_#x2013 G Quantitative data of the expression of iNOS TNF-_amp_#x3b1 Bcl-2 cleaved caspase-3 and cleaved PARP in five groups 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11142 18436268 12894 16068 270 PARP1 PARP PARP 14 1.9 the expression of iNOS TNF-_amp_#x3b1 Bcl-2 cleaved caspase-3 and cleaved PARP in five groups 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000860606472625916<>ScoreDetail__2187|COL11A2|0.000418935902806871__270|PARP1|0.000860606472625916__ 0 0 0 0 0 11143 18436268 12895 20996 11179 SOD1 SOD1 SOD1 34 3.4 and ## P _amp_#x3c 0.001 (when when compared with the SOD1 group * N in each group = 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11733 18459454 13786 4708 2187 COL11A2 PARP PARP 0 2.4 PARP activation and inflammatory reaction in selective neurodegeneration 1 JUMiner_v2.2 1 0 0 2 270 TotalCon:2<>270|PARP1|142|Complete__2187|COL11A2|1302|Complete__<>AvaiableGeneRif=2<>BEST:270|PARP1|0.000526870389884088<>ScoreDetail__2187|COL11A2|0__270|PARP1|0.000526870389884088__ 0 0 0 0 0 11940 18464922 14213 20996 11179 SOD1 ALS ALS 4 1.1 Abstract Amyotrophic lateral sclerosis (ALS) ALS is a debilitating and one of the most common adult-onset 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11941 18464922 14215 20996 11179 SOD1 ALS ALS 0 1.1 ALS has an obscure cause and currently no effective treatment exists 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11942 18464922 14216 17034 9236 PPARG PPAR PPAR-G 18 2.2 is described that can be activated by peroxisome proliferator-activated receptor-_amp_#x003b3 PPAR-_amp_#x003b3 agonists and has the ability to block the neuropathological damage 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11943 18464922 14216 20996 11179 SOD1 ALS ALS 35 1.1 ability to block the neuropathological damage caused by inflammation in ALS and possibly in other neudegenerative diseases like Huntington's disease (HD) 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11944 18464922 14218 17034 9236 PPARG PPAR PPAR-G 1 2.2 Therefore PPAR-_amp_#x003b3 agonists are thought to be neuroprotective in ALS and HD 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11945 18464922 14218 20996 11179 SOD1 ALS ALS 10 1.1 Therefore PPAR-_amp_#x003b3 agonists are thought to be neuroprotective in ALS and HD 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11946 18464922 14219 17034 9236 PPARG PPAR PPAR-G 12 2.2 have tested the neuroprotective effect of pioglitazone (Actos), Actos a PPAR-_amp_#x003b3 agonist in G93A SOD1 transgenic mouse model of ALS and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11947 18464922 14219 20996 11179 SOD1 SOD1 SOD1 17 0.5 effect of pioglitazone (Actos), Actos a PPAR-_amp_#x003b3 agonist in G93A SOD1 transgenic mouse model of ALS and found significant increase in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11948 18464922 14219 20996 11179 SOD1 ALS ALS 22 1.1 a PPAR-_amp_#x003b3 agonist in G93A SOD1 transgenic mouse model of ALS and found significant increase in survival of G93A SOD1 mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11949 18464922 14219 20996 11179 SOD1 SOD1 SOD1 31 0.5 of ALS and found significant increase in survival of G93A SOD1 mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11950 18464922 14220 17034 9236 PPARG PPAR PPAR-G 4 2.2 These findings suggest that PPAR-_amp_#x003b3 may be an important regulator of neuroinflammation and possibly a 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11951 18464922 14220 20996 11179 SOD1 ALS ALS 25 1.1 a new target for the development of therapeutic strategies for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11952 18464922 14221 17034 9236 PPARG PPAR PPAR-G 3 2.2 The involvement of PPAR-_amp_#x003b3 in HD is currently under investigation one study finds that 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11953 18464922 14222 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 coactivator-1 _amp_#x003b1 (PGC-1 PGC-1 _amp_#x003b1 is a transcriptional coactivator that 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11954 18464922 14222 17035 9237 PPARGC1A PGC1 PGC-1 4 1.2 PPAR-_amp_#x003b3 coactivator-1 _amp_#x003b1 (PGC-1 PGC-1 _amp_#x003b1 is a transcriptional coactivator that works together with combination 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11955 18464922 14222 17034 9236 PPARG PPAR PPAR-G 21 2.2 that works together with combination of other transcription factors like PPAR-_amp_#x003b3 in the regulation of mitochondrial biogenesis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11956 18464922 14223 17034 9236 PPARG PPAR PPAR-G 1 2.2 Therefore PPAR-_amp_#x003b3 is a possible target for ALS and HD as it 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11957 18464922 14223 20996 11179 SOD1 ALS ALS 8 1.1 Therefore PPAR-_amp_#x003b3 is a possible target for ALS and HD as it functions as transcription factor that interacts 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11958 18464922 14223 17035 9237 PPARGC1A PGC1 PGC-1 20 1.2 HD as it functions as transcription factor that interacts with PGC-1 _amp_#x003b1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11959 18464922 14224 17034 9236 PPARG PPAR PPAR-G 6 2.2 In this review the role of PPAR-_amp_#x003b3 in ALS and HD is discussed based on the current 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11960 18464922 14224 20996 11179 SOD1 ALS ALS 9 1.1 In this review the role of PPAR-_amp_#x003b3 in ALS and HD is discussed based on the current literature and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11961 18464922 14227 17031 9232 PPARA PPAR PPARs 3 2.2 Peroxisome proliferator-activated receptors (PPARs) PPARs are ligand-activated transcription factors that belong to the nuclear hormone 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11962 18464922 14227 17034 9236 PPARG PPAR PPAR-G 18 2.2 that belong to the nuclear hormone receptor superfamily which includes PPAR-_amp_#x003b3 PPAR-_amp_#x003b1 and PPAR-_amp_#x003b2 / _amp_#x003b4 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11963 18464922 14227 17031 9232 PPARA PPAR PPAR-A 21 2.2 belong to the nuclear hormone receptor superfamily which includes PPAR-_amp_#x003b3 PPAR-_amp_#x003b1 and PPAR-_amp_#x003b2 / _amp_#x003b4 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11964 18464922 14227 17033 9235 PPARD PPAR PPAR-B 25 2.2 the nuclear hormone receptor superfamily which includes PPAR-_amp_#x003b3 PPAR-_amp_#x003b1 and PPAR-_amp_#x003b2 / _amp_#x003b4 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11965 18464922 14228 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 is the most studied receptor and has two isoforms produced 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11966 18464922 14228 17034 9236 PPARG PPAR PPAR-G 20 2.2 isoforms produced due to alternative splicing and alternate translation initiation PPAR-_amp_#x003b3 1 and PPAR-_amp_#x003b3 2 1 2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11967 18464922 14228 17034 9236 PPARG PPAR PPAR-G 24 2.2 to alternative splicing and alternate translation initiation PPAR-_amp_#x003b3 1 and PPAR-_amp_#x003b3 2 1 2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11968 18464922 14229 17031 9232 PPARA PPAR PPARs 16 2.2 receptor from the same superfamily that forms heterodimeric complexes with PPARs in response to ligand binding 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11969 18464922 14231 17031 9232 PPARA PPAR PPARs 0 2.2 PPARs are ligand-dependent transcription factors that bind to specific PPREs and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11970 18464922 14232 17031 9232 PPARA PPAR PPARs 0 2.2 PPARs regulate the expression of target genes in particular those associated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11971 18464922 14233 17031 9232 PPARA PPAR PPAR 0 2.5 PPAR isotypes appear to exhibit distinct patterns of tissue distribution and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11972 18464922 14234 17031 9232 PPARA PPAR PPAR-A 0 2.2 PPAR-_amp_#x003b1 is expressed in high levels in hepatocytes entrocytes and kidney 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11973 18464922 14235 17031 9232 PPARA PPAR PPAR-A 0 2.2 PPAR-_amp_#x003b1 is implicated to be responsible for the peroxisome proliferator-induced pleiotropic 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11974 18464922 14236 17031 9232 PPARA PPAR PPAR-A 0 2.2 PPAR-_amp_#x003b1 and _amp_#x003b4 appear primarily to stimulate oxidative lipid metabolism while 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11975 18464922 14236 17034 9236 PPARG PPAR PPAR-G 12 2.2 and _amp_#x003b4 appear primarily to stimulate oxidative lipid metabolism while PPAR-_amp_#x003b3 is principally involved in the cellular assimilation of lipids via 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11976 18464922 14237 17034 9236 PPARG PPAR PPAR-G 4 2.2 Recently other functions for PPAR-_amp_#x003b3 are described such as neuroprotection in ischemia 15 and its 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11977 18464922 14238 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 has been demonstrated to be involved in adipogenesis and differentiation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11978 18464922 14239 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 is shown to have a vital role in adipocyte differentiation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11979 18464922 14240 17034 9236 PPARG PPAR PPAR-G 3 2.2 Recent studies demonstrate PPAR-_amp_#x003b3 agonists to prevent inflammation and neuronal death after focal cerebral 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11980 18464922 14241 17034 9236 PPARG PPAR PPAR-G 7 2.2 Thiazolidinediones (TZDs) TZDs are potent synthetic agonists of PPAR-_amp_#x003b3 shown to induce neuroprotection after cerebral ischemia by blocking inflammation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11981 18464922 14244 17034 9236 PPARG PPAR PPAR-G 13 2.2 protective lipid-independent effects of TZDs are the anti-inflammatory capacities of PPAR-_amp_#x003b3 4 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11982 18464922 14245 14535 7873 NOS2A iNOS iNOS 13 2.2 of various inflammatory proteins like inducible nitric oxide synthase (iNOS), iNOS tumor necrosis factor-_amp_#x003b1 TNF-_amp_#x003b1 and matrix metalloproteinase-9 (MMP-9) MMP-9 in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11983 18464922 14245 22551 11892 TNF TNF TNF-A 18 1.2 like inducible nitric oxide synthase (iNOS), iNOS tumor necrosis factor-_amp_#x003b1 TNF-_amp_#x003b1 and matrix metalloproteinase-9 (MMP-9) MMP-9 in macrophages 26 and are 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11984 18464922 14245 13327 7176 MMP9 MMP-9 MMP-9 24 1.3 (iNOS), iNOS tumor necrosis factor-_amp_#x003b1 TNF-_amp_#x003b1 and matrix metalloproteinase-9 (MMP-9) MMP-9 in macrophages 26 and are beneficial in disorders such as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11985 18464922 14246 20996 11179 SOD1 ALS ALS 16 1.1 be neurotoxic in models of neurodegenerative diseases for example in ALS 28 _amp_#x02013 30 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11986 18464922 14247 7683 3796 FOS AP-1 AP-1 18 1.0 of nuclear factor kappa B NF-_amp_#x003ba B activator protein-1 (AP-1), AP-1 in addition to signal transducers and activators of transcription (STAT) 1 JUMiner_v2.2 1 0 0 2 6204 TotalCon:5<>3796|FOS|2353|Complete__3797|FOSB|2354|Complete__6204|JUN|3725|Complete__6205|JUNB|3726|Complete__6206|JUND|3727|Complete__<>AvaiableGeneRif=5<>BEST:6204|JUN|0.000585601005651176<>ScoreDetail__3796|FOS|0.000569072445989232__3797|FOSB|0.000411900390716942__6205|JUNB|0.00050943910584066__6204|JUN|0.000585601005651176__6206|JUND|0.000575662278130164__ 0 0 0 0 0 11987 18464922 14247 21414 11362 STAT1 STAT STAT 28 2.1 in addition to signal transducers and activators of transcription (STAT) STAT transcription factors by PPAR-_amp_#x003b3 31 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11988 18464922 14247 17034 9236 PPARG PPAR PPAR-G 32 2.2 transducers and activators of transcription (STAT) STAT transcription factors by PPAR-_amp_#x003b3 31 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11989 18464922 14249 17034 9236 PPARG PPAR PPAR-G 4 2.2 It is possible that PPAR-_amp_#x003b3 is involved in the reciprocal inhibition of differential transcription systems 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11990 18464922 14250 17034 9236 PPARG PPAR PPAR-G 11 2.2 an alternative mechanism suggested that a functionally distinct pool of PPAR-_amp_#x003b3 is susceptible to ligand-dependent sumoylation (covalent covalent attachment of small 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11991 18464922 14250 14187 7672 NCOR1 N-CoR N-CoR 35 1.3 365 leading to recruitment and stabilization of nuclear corepressor (N-CoR) N-CoR complexes at the promoters of proinflammatory genes thereby repressing them 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11992 18464922 14255 17031 9232 PPARA PPAR PPAR 5 2.5 Figure 1 (a) a Structure of PPAR agonists (b) b schematic diagrams linking mechanisms of neuronal cell 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11993 18464922 14255 20996 11179 SOD1 ALS ALS 17 1.1 b schematic diagrams linking mechanisms of neuronal cell death in ALS and a representation of PPAR-_amp_#x003b3 activation 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11994 18464922 14255 17034 9236 PPARG PPAR PPAR-G 22 2.2 of neuronal cell death in ALS and a representation of PPAR-_amp_#x003b3 activation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11995 18464922 14256 20996 11179 SOD1 ALS ALS 9 1.1 The mechanisms and pathways implicated in the pathogenesis of ALS that lead to the demise of motor (more more ... 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11996 18464922 14258 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 AND AMYOTROPHIC LATERAL SCLEROSIS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 11997 18464922 14259 20996 11179 SOD1 ALS ALS 3 1.1 Amyotrophic lateral sclerosis (ALS) ALS is a devastating fatal neurodegenerative disorder characterized by a loss 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11998 18464922 14260 20996 11179 SOD1 ALS ALS 10 1.1 Oxidative stress mitochondrial dysfunction and neuroinflammation have been implicated in ALS pathogenesis ( Figure 1(b) 1 b 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 11999 18464922 14261 17031 9232 PPARA PPAR PPARs 0 2.2 PPARs in particular PPAR-_amp_#x003b3 may be a major signaling pathway involved 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12000 18464922 14261 17034 9236 PPARG PPAR PPAR-G 3 2.2 PPARs in particular PPAR-_amp_#x003b3 may be a major signaling pathway involved in neuroinflammation in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12001 18464922 14261 20996 11179 SOD1 ALS ALS 16 1.1 may be a major signaling pathway involved in neuroinflammation in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12002 18464922 14262 17034 9236 PPARG PPAR PPAR-G 5 2.2 The activation or inactivation of PPAR-_amp_#x003b3 could provide a viable and promising approach to understand the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12003 18464922 14262 20996 11179 SOD1 ALS ALS 21 1.1 and promising approach to understand the mechanism of neuroinflammation in ALS ( Figure 1(b) 1 b 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12004 18464922 14263 20996 11179 SOD1 ALS ALS 10 1.1 Since neuroinflammatory pathway has become one of the hallmarks of ALS 29 33 34 therefore blockage of neuroinflammation is of great 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12005 18464922 14263 20996 11179 SOD1 ALS ALS 32 1.1 is of great interest because of the potential efficacy in ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12006 18464922 14264 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 has been identified as a key regulatory factor in the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12007 18464922 14264 17031 9232 PPARA PPAR PPAR 17 2.5 key regulatory factor in the modulation of target genes with PPAR response element (PPRE) PPRE in their promoters including those encoding 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12008 18464922 14264 14535 7873 NOS2A iNOS iNOS 29 2.2 PPRE in their promoters including those encoding for inflammation (iNOS, iNOS NF-_amp_#x003ba B COX-2 oxidative stress and apoptosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12009 18464922 14264 17610 9605 PTGS2 COX-2 COX-2 33 1.0 promoters including those encoding for inflammation (iNOS, iNOS NF-_amp_#x003ba B COX-2 oxidative stress and apoptosis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12010 18464922 14265 17034 9236 PPARG PPAR PPAR-G 1 2.2 Synthetic PPAR-_amp_#x003b3 agonists developed in the past 25 years that are used 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12011 18464922 14265 17034 9236 PPARG PPAR PPAR-G 28 2.2 suitable candidates and are indispensable to study the role of PPAR-_amp_#x003b3 in ALS which may potentially lead to beneficial effects in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12012 18464922 14265 20996 11179 SOD1 ALS ALS 31 1.1 and are indispensable to study the role of PPAR-_amp_#x003b3 in ALS which may potentially lead to beneficial effects in ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12013 18464922 14265 20996 11179 SOD1 ALS ALS 40 1.1 in ALS which may potentially lead to beneficial effects in ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12014 18464922 14266 17034 9236 PPARG PPAR PPAR-G 8 2.2 Previous studies have shown the protective effect of PPAR-_amp_#x003b3 agonists in many experimental models such as in experimental autoimmune 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12015 18464922 14267 17034 9236 PPARG PPAR PPAR-G 1 2.2 Additionally PPAR-_amp_#x003b3 agonists are reported to be neuroprotective in tyrosine hydroxylase positive 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12016 18464922 14269 20996 11179 SOD1 ALS ALS 4 1.1 PIOGLITAZONE IS NEUROPROTECTIVE IN ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12017 18464922 14270 20996 11179 SOD1 SOD1 SOD1 11 0.5 have tested the neuroprotective effect of pioglitazone in transgenic G93A SOD1 mouse model of ALS and showed that pioglitazone treatment improved 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12018 18464922 14270 20996 11179 SOD1 ALS ALS 15 1.1 effect of pioglitazone in transgenic G93A SOD1 mouse model of ALS and showed that pioglitazone treatment improved motor performance delayed weight 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12019 18464922 14270 20996 11179 SOD1 ALS ALS 40 1.1 loss and significantly increased survival by delaying the onset of ALS 38 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12020 18464922 14271 3889 11919 CD40 CD40 CD40 22 0.6 in the spinal cord as assessed by immunohistochemical staining for CD40 (microglia microglia marker and GFAP (astrocyte astrocyte marker respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12021 18464922 14271 8254 4235 GFAP GFAP GFAP 26 0.3 assessed by immunohistochemical staining for CD40 (microglia microglia marker and GFAP (astrocyte astrocyte marker respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12022 18464922 14272 14535 7873 NOS2A iNOS iNOS 7 2.2 Furthermore we showed that pioglitazone treatment reduced iNOS NF-_amp_#x003ba B and 3-nitotyrosine immunoreactivity in the spinal cord of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12023 18464922 14273 20996 11179 SOD1 SOD1 SOD1 16 0.5 another study on the effect of pioglitazone treatment in G93A SOD1 transgenic mouse model of ALS 39 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12024 18464922 14273 20996 11179 SOD1 ALS ALS 21 1.1 of pioglitazone treatment in G93A SOD1 transgenic mouse model of ALS 39 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12025 18464922 14274 17034 9236 PPARG PPAR PPAR-G 3 2.2 In this study PPAR-_amp_#x003b3 agonist treatment improved survival muscle strength and weight loss in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12026 18464922 14274 20996 11179 SOD1 ALS ALS 15 1.1 agonist treatment improved survival muscle strength and weight loss in ALS mice 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12027 18464922 14277 17610 9605 PTGS2 COX-2 COX-2 16 1.0 microglial activation as well as reduction in the expression of COX-2 and iNOS 39 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12028 18464922 14277 14535 7873 NOS2A iNOS iNOS 18 2.2 as well as reduction in the expression of COX-2 and iNOS 39 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12029 18464922 14278 20987 19383 SOCS1 SOCS-1 SOCS-1 33 3.5 suppressor genes suppressor of cytokine signaling 1 and 3 (SOCS-1 SOCS-1 and -3 were increased as assessed by semiquantitative RT-PCR 39 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12030 18464922 14278 20991 19391 SOCS3 SOCS-3 SOCS-3 33 1.5 suppressor genes suppressor of cytokine signaling 1 and 3 (SOCS-1 SOCS-1 and -3 were increased as assessed by semiquantitative RT-PCR 39 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12031 18464922 14279 20987 19383 SOCS1 SOCS-1 SOCS-1 6 3.5 Others have reported similar increase in SOCS-1 and -3 in response to TZDs in microglia and astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12032 18464922 14279 20991 19391 SOCS3 SOCS-3 SOCS-3 6 1.5 Others have reported similar increase in SOCS-1 and -3 in response to TZDs in microglia and astrocytes 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12033 18464922 14280 20987 19383 SOCS1 SOCS-1 SOCS-1 3 3.5 The increase in SOCS-1 and -3 is implicated with the inhibition of Janus kinase-signal 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12034 18464922 14280 20991 19391 SOCS3 SOCS-3 SOCS-3 3 1.5 The increase in SOCS-1 and -3 is implicated with the inhibition of Janus kinase-signal 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12035 18464922 14281 17034 9236 PPARG PPAR PPAR-G 3 2.2 Other studies using PPAR-_amp_#x003b3 agonists suggest that the mechanism of actions are also by 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12036 18464922 14282 17034 9236 PPARG PPAR PPAR-G 6 2.2 Recently Xu and Drew demonstrated that PPAR-_amp_#x003b3 agonists suppress cytokines like IL-12 family in EAE an experimental 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12037 18464922 14283 17034 9236 PPARG PPAR PPAR-G 5 2.2 These studies provide evidence that PPAR-_amp_#x003b3 agonist responses are originating from activated glial cells in central 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12038 18464922 14284 17031 9232 PPARA PPAR PPAR 0 2.5 PPAR agonists are shown to modulate microglia and astrocytes in central 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12039 18464922 14285 17034 9236 PPARG PPAR PPAR-G 15 2.2 showed reduction in gliosis which is another experimental evidence that PPAR-_amp_#x003b3 acts on glial cells in CNS 38 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12040 18464922 14286 17034 9236 PPARG PPAR PPAR-G 3 2.2 The action of PPAR-_amp_#x003b3 in neuronal cells needs to be studied 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12041 18464922 14287 17034 9236 PPARG PPAR PPAR-G 8 2.2 The preliminary reports on the neuroprotective role of PPAR-_amp_#x003b3 agonist in transgenic mouse model of ALS and other experimental 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12042 18464922 14287 20996 11179 SOD1 ALS ALS 16 1.1 neuroprotective role of PPAR-_amp_#x003b3 agonist in transgenic mouse model of ALS and other experimental animal models could potentially be a foundation 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12043 18464922 14287 17031 9232 PPARA PPAR PPARs 40 2.2 of studies to understand the mechanism and molecular details of PPARs and their role in protecting motor neurons from inflammatory damages 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12044 18464922 14287 20996 11179 SOD1 ALS ALS 52 1.1 their role in protecting motor neurons from inflammatory damages in ALS ( Figure 1(b) 1 b 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12045 18464922 14288 17034 9236 PPARG PPAR PPAR-G 4 2.2 The mechanisms of how PPAR-_amp_#x003b3 agonists induce neuroprotection by blocking neuroinflammation is not fully understood 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12046 18464922 14288 17034 9236 PPARG PPAR PPAR-G 24 2.2 fully understood and further information on the molecular details of PPAR-_amp_#x003b3 in neuroinflammatory pathways will provide crucial insights on the role 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12047 18464922 14288 17034 9236 PPARG PPAR PPAR-G 37 2.2 neuroinflammatory pathways will provide crucial insights on the role of PPAR-_amp_#x003b3 in ALS and other neurodegenerative diseases 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12048 18464922 14288 20996 11179 SOD1 ALS ALS 40 1.1 will provide crucial insights on the role of PPAR-_amp_#x003b3 in ALS and other neurodegenerative diseases 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12049 18464922 14290 20996 11179 SOD1 ALS ALS 3 1.1 MITOCHONDRIAL DYSFUNCTION IN ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12050 18464922 14291 20996 11179 SOD1 ALS ALS 3 1.1 Mitochondrial compromise in ALS is substantiated by reports of changes in their structure number 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12051 18464922 14291 20996 11179 SOD1 ALS ALS 26 1.1 in motor neurons and skeletal muscle in familial and sporadic ALS patients 42 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12052 18464922 14292 20996 11179 SOD1 ALS ALS 12 1.1 reported the potential involvement of mitochondria in the pathogenesis of ALS as mitochondrial abnormalities were found in proximal axons anterior horn 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12053 18464922 14292 20996 11179 SOD1 ALS ALS 24 1.1 mitochondrial abnormalities were found in proximal axons anterior horn of ALS spinal cords 43 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12054 18464922 14293 20996 11179 SOD1 ALS ALS 16 1.1 have been detected in postmortem muscle and spinal cord of ALS patients 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12055 18464922 14294 20996 11179 SOD1 SOD1 SOD1 14 0.5 of mitochondrial dysfunction in FALS-SOD1 it is hypothesized that mutant SOD1 may directly damage mitochondrial function and integrity 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12056 18464922 14295 20996 11179 SOD1 SOD1 SOD1 10 0.5 Several studies have shown that transgenic mice overexpressing human G93A SOD1 that display most of the ALS symptoms and pathologies have 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12057 18464922 14295 20996 11179 SOD1 ALS ALS 16 1.1 mice overexpressing human G93A SOD1 that display most of the ALS symptoms and pathologies have mitochondrial dysfunction 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12058 18464922 14298 20996 11179 SOD1 ALS ALS 11 1.1 observations suggest that mitochondrial abnormalities may trigger the onset of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12059 18464922 14299 20996 11179 SOD1 SOD1 SOD1 11 0.5 we and others have shown that wild type and mutant SOD1 are found within mitochondrion which was known to be a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12060 18464922 14300 20996 11179 SOD1 SOD1 SOD1 1 0.5 How SOD1 is interacting with mitochondria is unclear and it is being 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12061 18464922 14301 20996 11179 SOD1 SOD1 SOD1 5 0.5 The toxic action of mutant SOD1 in and out of mitochondria could be partly explained as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12062 18464922 14302 20996 11179 SOD1 SOD1 SOD1 6 0.5 (i) i Mutant but not wild type SOD1 binds to heat shock proteins causing an inhibition of chaperon 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12063 18464922 14303 20996 11179 SOD1 SOD1 SOD1 5 0.5 Both mutant and wild type SOD1 bind to antiapoptotic protein Bcl-2 on the outer mitochondrial membrane 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12064 18464922 14303 1576 990 BCL2 Bcl-2 Bcl-2 10 1.8 Both mutant and wild type SOD1 bind to antiapoptotic protein Bcl-2 on the outer mitochondrial membrane blocking its antiapoptotic activity 42 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12065 18464922 14304 20996 11179 SOD1 SOD1 SOD1 5 0.5 (ii) ii The presence of mutant SOD1 in the mitochondria leads to formation of SOD1 aggregates entrapping 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12066 18464922 14304 20996 11179 SOD1 SOD1 SOD1 13 0.5 of mutant SOD1 in the mitochondria leads to formation of SOD1 aggregates entrapping Bcl-2 blocking protein importation to mitochondria which may 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12067 18464922 14304 1576 990 BCL2 Bcl-2 Bcl-2 16 1.8 in the mitochondria leads to formation of SOD1 aggregates entrapping Bcl-2 blocking protein importation to mitochondria which may trigger neuronal cell 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12068 18464922 14305 17035 9237 PPARGC1A PGC1 PGC-1 1 1.2 Since PGC-1 _amp_#x003b1 is known to coordinate mitochondrial biogenesis and regulates mitochondrial 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12069 18464922 14305 17035 9237 PPARGC1A PGC1 PGC-1 19 1.2 and regulates mitochondrial function it is possible to predict that PGC-1 _amp_#x003b1 could play an important role in ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12070 18464922 14305 20996 11179 SOD1 ALS ALS 27 1.1 predict that PGC-1 _amp_#x003b1 could play an important role in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12071 18464922 14306 17035 9237 PPARGC1A PGC1 PGC-1 2 1.2 Impairment of PGC-1 _amp_#x003b1 could contribute to mitochondrial dysfunction in ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12072 18464922 14306 20996 11179 SOD1 ALS ALS 10 1.1 Impairment of PGC-1 _amp_#x003b1 could contribute to mitochondrial dysfunction in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12073 18464922 14307 17035 9237 PPARGC1A PGC1 PGC-1 11 1.2 date there is no published data on the role of PGC-1 _amp_#x003b1 or its expression in the transgenic mouse model of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12074 18464922 14307 20996 11179 SOD1 ALS ALS 22 1.1 _amp_#x003b1 or its expression in the transgenic mouse model of ALS or human ALS postmortem tissues 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12075 18464922 14307 20996 11179 SOD1 ALS ALS 25 1.1 expression in the transgenic mouse model of ALS or human ALS postmortem tissues 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12076 18464922 14308 20996 11179 SOD1 ALS ALS 13 1.1 reports on the altered or impaired expression of genes in ALS that some of them fit in the PGC-1 _amp_#x003b1 target 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12077 18464922 14308 17035 9237 PPARGC1A PGC1 PGC-1 21 1.2 genes in ALS that some of them fit in the PGC-1 _amp_#x003b1 target genes category 29 48 suggesting that there may 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12078 18464922 14308 17035 9237 PPARGC1A PGC1 PGC-1 40 1.2 48 suggesting that there may be a prominent role for PGC-1 _amp_#x003b1 translational machinery in ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12079 18464922 14308 20996 11179 SOD1 ALS ALS 45 1.1 be a prominent role for PGC-1 _amp_#x003b1 translational machinery in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12080 18464922 14309 17035 9237 PPARGC1A PGC1 PGC-1 1 1.2 Since PGC-1 _amp_#x003b1 is a PPAR-_amp_#x003b3 coactivator it is possible that PPAR-_amp_#x003b3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12081 18464922 14309 17034 9236 PPARG PPAR PPAR-G 5 2.2 Since PGC-1 _amp_#x003b1 is a PPAR-_amp_#x003b3 coactivator it is possible that PPAR-_amp_#x003b3 agonists may be able 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12082 18464922 14309 17034 9236 PPARG PPAR PPAR-G 12 2.2 PGC-1 _amp_#x003b1 is a PPAR-_amp_#x003b3 coactivator it is possible that PPAR-_amp_#x003b3 agonists may be able to activate PGC-1 _amp_#x003b1 and also 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12083 18464922 14309 17035 9237 PPARGC1A PGC1 PGC-1 20 1.2 is possible that PPAR-_amp_#x003b3 agonists may be able to activate PGC-1 _amp_#x003b1 and also the PGC-1 _amp_#x003b1 target genes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12084 18464922 14309 17035 9237 PPARGC1A PGC1 PGC-1 25 1.2 may be able to activate PGC-1 _amp_#x003b1 and also the PGC-1 _amp_#x003b1 target genes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12085 18464922 14310 17035 9237 PPARGC1A PGC1 PGC-1 6 1.2 Like in HD a reduction of PGC-1 _amp_#x003b1 and its target genes expression is attributed to mutant 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12086 18464922 14310 20996 11179 SOD1 SOD1 SOD1 20 0.5 target genes expression is attributed to mutant huntingtin similarly mutant SOD1 could impair PGC-1 _amp_#x003b1 and expression of its target genes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12087 18464922 14310 17035 9237 PPARGC1A PGC1 PGC-1 23 1.2 is attributed to mutant huntingtin similarly mutant SOD1 could impair PGC-1 _amp_#x003b1 and expression of its target genes in ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12088 18464922 14310 20996 11179 SOD1 ALS ALS 32 1.1 impair PGC-1 _amp_#x003b1 and expression of its target genes in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12089 18464922 14311 20996 11179 SOD1 SOD1 SOD1 2 0.5 Whether mutant SOD1 can impair PPAR-_amp_#x003b3 is yet to be determined 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12090 18464922 14311 17034 9236 PPARG PPAR PPAR-G 5 2.2 Whether mutant SOD1 can impair PPAR-_amp_#x003b3 is yet to be determined 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12091 18464922 14312 17035 9237 PPARGC1A PGC1 PGC-1 3 1.2 Future studies on PGC-1 _amp_#x003b1 and PPAR-_amp_#x003b3 in ALS patients and transgenic mice will 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12092 18464922 14312 17034 9236 PPARG PPAR PPAR-G 6 2.2 Future studies on PGC-1 _amp_#x003b1 and PPAR-_amp_#x003b3 in ALS patients and transgenic mice will shed some lights 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12093 18464922 14312 20996 11179 SOD1 ALS ALS 9 1.1 Future studies on PGC-1 _amp_#x003b1 and PPAR-_amp_#x003b3 in ALS patients and transgenic mice will shed some lights on these 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12094 18464922 14314 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 AND HUNTINGTON'S DISEASE 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12095 18464922 14320 17034 9236 PPARG PPAR PPAR-G 9 2.2 Recent reports show that mutant huntingtin interferes with transcriptional PPAR-_amp_#x003b3 coactivator-1 _amp_#x003b1 (PGC-1 PGC-1 _amp_#x003b1 causing impairment on its function 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12096 18464922 14320 17035 9237 PPARGC1A PGC1 PGC-1 13 1.2 that mutant huntingtin interferes with transcriptional PPAR-_amp_#x003b3 coactivator-1 _amp_#x003b1 (PGC-1 PGC-1 _amp_#x003b1 causing impairment on its function in HD suggesting that 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12097 18464922 14320 17035 9237 PPARGC1A PGC1 PGC-1 34 1.2 that mutant huntingtin plays a role in the dysregulation of PGC-1 _amp_#x003b1 -mediated transcription and activity impairing mitochondrial function and leading 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12098 18464922 14321 17035 9237 PPARGC1A PGC1 PGC-1 5 1.2 Weydt et al found that PGC-1 _amp_#x003b1 target genes (NDUFS3, NDUFS3 CYCS COX6A1 NDUFB5 ACADM TFAM 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12099 18464922 14321 5284 19986 CYCS CYCS CYCS 10 0.3 et al found that PGC-1 _amp_#x003b1 target genes (NDUFS3, NDUFS3 CYCS COX6A1 NDUFB5 ACADM TFAM and LDHB had reduced expression in 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12100 18464922 14321 4805 2277 COX6A1 COX6A1 COX6A1 11 0.3 al found that PGC-1 _amp_#x003b1 target genes (NDUFS3, NDUFS3 CYCS COX6A1 NDUFB5 ACADM TFAM and LDHB had reduced expression in HD 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12101 18464922 14321 22024 11741 TFAM TFAM TFAM 14 0.9 PGC-1 _amp_#x003b1 target genes (NDUFS3, NDUFS3 CYCS COX6A1 NDUFB5 ACADM TFAM and LDHB had reduced expression in HD patient and mouse 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12102 18464922 14321 14256 7710 NDUFS3 NDUFS3 NDUFS3 9 0.3 Weydt et al found that PGC-1 _amp_#x003b1 target genes (NDUFS3, NDUFS3 CYCS COX6A1 NDUFB5 ACADM TFAM and LDHB had reduced expression 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12103 18464922 14321 14241 7700 NDUFB5 NDUFB5 NDUFB5 12 0.4 found that PGC-1 _amp_#x003b1 target genes (NDUFS3, NDUFS3 CYCS COX6A1 NDUFB5 ACADM TFAM and LDHB had reduced expression in HD patient 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12104 18464922 14321 137 89 ACADM ACADM ACADM 13 0.3 that PGC-1 _amp_#x003b1 target genes (NDUFS3, NDUFS3 CYCS COX6A1 NDUFB5 ACADM TFAM and LDHB had reduced expression in HD patient and 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12105 18464922 14321 11731 6541 LDHB LDHB LDHB 16 0.1 target genes (NDUFS3, NDUFS3 CYCS COX6A1 NDUFB5 ACADM TFAM and LDHB had reduced expression in HD patient and mouse striatum 27 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12106 18464922 14323 17035 9237 PPARGC1A PGC1 PGC-1 6 1.2 An interesting finding was that the PGC-1 _amp_#x003b1 and uncoupling protein 1 (UCP-1) UCP-1 circuit was found 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12107 18464922 14323 23632 12517 UCP1 UCP1 UCP-1 12 1.4 was that the PGC-1 _amp_#x003b1 and uncoupling protein 1 (UCP-1) UCP-1 circuit was found to be disrupted in the brown adipose 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12108 18464922 14323 1489 932 BAAT BAT BAT 24 0.0 found to be disrupted in the brown adipose tissue (BAT) BAT of HD transgenic mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12109 18464922 14326 1489 932 BAAT BAT BAT 2 0.0 In rodents BAT is the tissue that responds to cold 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12110 18464922 14327 17035 9237 PPARGC1A PGC1 PGC-1 9 1.2 In HD and wild type mice challenged with cold PGC-1 _amp_#x003b1 expression increased but in HD mice UCP-1 expression was 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12111 18464922 14327 23632 12517 UCP1 UCP1 UCP-1 17 1.4 with cold PGC-1 _amp_#x003b1 expression increased but in HD mice UCP-1 expression was not upregulated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12112 18464922 14328 17035 9237 PPARGC1A PGC1 PGC-1 4 1.2 However they showed that PGC-1 _amp_#x003b1 expression is decreased in the striatum of human HD 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12113 18464922 14329 17031 9232 PPARA PPAR PPAR-A 9 2.2 They also examined the expression of unclear hormone receptors PPAR-_amp_#x003b1 RXR-_amp_#x003b1 and transcription factors (NRF-1) NRF-1 that known to rely 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12114 18464922 14329 14668 7996 NRF1 NRF1 NRF-1 18 1.2 of unclear hormone receptors PPAR-_amp_#x003b1 RXR-_amp_#x003b1 and transcription factors (NRF-1) NRF-1 that known to rely upon PGC-1 _amp_#x003b1 for target gene 11 JUMiner_v2.2 1 0 0 2 7996 TotalCon:2<>7996|NRF1|4899|Complete__7781|NFE2L1|4779|Complete__<>AvaiableGeneRif=2<>BEST:7996|NRF1|0.0009632528810611<>ScoreDetail__7781|NFE2L1|0.000858132577546843__7996|NRF1|0.0009632528810611__ 0 0 0 0 0 12115 18464922 14329 17035 9237 PPARGC1A PGC1 PGC-1 24 1.2 and transcription factors (NRF-1) NRF-1 that known to rely upon PGC-1 _amp_#x003b1 for target gene activation these genes were upregulated suggesting 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12116 18464922 14329 17035 9237 PPARGC1A PGC1 PGC-1 39 1.2 activation these genes were upregulated suggesting possible compensatory upregulation of PGC-1 _amp_#x003b1 -dependent transcription factors in human HD caudate 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12117 18464922 14331 17035 9237 PPARGC1A PGC1 PGC-1 15 1.2 et al studies provide further support that the reduction of PGC-1 _amp_#x003b1 and its target genes in HD striatum are caused 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12118 18464922 14332 17034 9236 PPARG PPAR PPAR-G 20 2.2 and R.E Hughes that their yeast two-hybrid screen identified that PPAR-_amp_#x003b3 is a huntingtin interactor and the interaction was validated for 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12119 18464922 14332 17034 9236 PPARG PPAR PPAR-G 40 2.2 validated for its biological significance by demonstrating an effect of PPAR-_amp_#x003b3 dosage upon HD neurodegeneration in the fly eye 27 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12120 18464922 14333 14535 7873 NOS2A iNOS iNOS 3 2.2 Increased levels of iNOS in HD 59 elevated oxidative damage products such as malondialdehyde 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12121 18464922 14334 17034 9236 PPARG PPAR PPAR-G 17 2.2 must be explored in order to understand the role of PPAR-_amp_#x003b3 and to identify new therapeutic targets for HD 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12122 18464922 14335 17034 9236 PPARG PPAR PPAR-G 2 2.2 Rosiglitazone (a a PPAR-_amp_#x003b3 agonist that induces sensitization to insulin was tested in R6/2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12123 18464922 14345 17034 9236 PPARG PPAR PPAR-G 34 2.2 2 mice it also provided data for the role of PPAR-_amp_#x003b3 in R6/2 R6 2 mice 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12124 18464922 14349 17290 9376 PRKAA1 AMPK AMPK 30 3.2 hepatic glucose synthesis 65 activation of AMP-activated protein kinase (AMPK, AMPK an enzyme involved in glucose and fatty acid metabolism 66 1 JUMiner_v2.2 1 0 0 2 9378 TotalCon:3<>9377|PRKAA2|5563|Complete__9376|PRKAA1|5562|Complete__9378|PRKAB1|5564|Complete__<>AvaiableGeneRif=3<>BEST:9378|PRKAB1|0.000657510402136462<>ScoreDetail__9377|PRKAA2|0.000637517136172011__9378|PRKAB1|0.000657510402136462__9376|PRKAA1|0.000571634565866722__ 0 0 0 0 0 12125 18464922 14350 17290 9376 PRKAA1 AMPK AMPK 2 3.2 Activation of AMPK is associated with mitochondrial proliferation and biogenesis 69 1 JUMiner_v2.2 1 0 0 2 9378 TotalCon:3<>9377|PRKAA2|5563|Complete__9376|PRKAA1|5562|Complete__9378|PRKAB1|5564|Complete__<>AvaiableGeneRif=3<>BEST:9378|PRKAB1|0.000657510402136462<>ScoreDetail__9377|PRKAA2|0.000637517136172011__9378|PRKAB1|0.000657510402136462__9376|PRKAA1|0.000571634565866722__ 0 0 0 0 0 12126 18464922 14351 17034 9236 PPARG PPAR PPAR-G 4 2.2 Rosiglitazone was used as PPAR-_amp_#x003b3 agonist in R6/2 R6 2 mice which could be used 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12127 18464922 14351 17034 9236 PPARG PPAR PPAR-G 22 2.2 be used as the bases to test the role of PPAR-_amp_#x003b3 in HD glibenclamide and metformin were used to treat atypical 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12128 18464922 14352 17290 9376 PRKAA1 AMPK AMPK 7 3.2 Metformin treatment in R6/2 R6 2 mice increased brain AMPK phosphorylation 62 although this needs to be confirmed 1 JUMiner_v2.2 1 0 0 2 9378 TotalCon:3<>9377|PRKAA2|5563|Complete__9376|PRKAA1|5562|Complete__9378|PRKAB1|5564|Complete__<>AvaiableGeneRif=3<>BEST:9378|PRKAB1|0.000657510402136462<>ScoreDetail__9377|PRKAA2|0.000637517136172011__9378|PRKAB1|0.000657510402136462__9376|PRKAA1|0.000571634565866722__ 0 0 0 0 0 12129 18464922 14353 17290 9376 PRKAA1 AMPK AMPK 2 3.2 Activation of AMPK leads to reduction in ATP-consuming processes and facilitate ATP-generating cellular 1 JUMiner_v2.2 1 0 0 2 9378 TotalCon:3<>9377|PRKAA2|5563|Complete__9376|PRKAA1|5562|Complete__9378|PRKAB1|5564|Complete__<>AvaiableGeneRif=3<>BEST:9378|PRKAB1|0.000657510402136462<>ScoreDetail__9377|PRKAA2|0.000637517136172011__9378|PRKAB1|0.000657510402136462__9376|PRKAA1|0.000571634565866722__ 0 0 0 0 0 12130 18464922 14356 17035 9237 PPARGC1A PGC1 PGC-1 19 1.2 be the synergistic effect from several pathways including regulation of PGC-1 _amp_#x003b1 activity through its direct activation of AMPA kinase 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12131 18464922 14358 17034 9236 PPARG PPAR PPAR-G 8 2.2 Metformin does not belong to any class of PPAR-_amp_#x003b3 agonists although it is an antidiabetic for type-2 diabetes and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12132 18464922 14359 17035 9237 PPARGC1A PGC1 PGC-1 0 1.2 PGC-1 _amp_#x003b1 has been implicated in mitochondrial biogenesis through its ability 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12133 18464922 14359 14668 7996 NRF1 NRF1 NRF-1 21 1.2 number of genes such as nuclear respiratory factor-1 -2 (NRF-1,-2), NRF-1 -2 estrogen related receptor _amp_#x003b1 (ERR ERR _amp_#x003b1 and mitochondrial 11 JUMiner_v2.2 1 0 0 2 7996 TotalCon:2<>7996|NRF1|4899|Complete__7781|NFE2L1|4779|Complete__<>AvaiableGeneRif=2<>BEST:7996|NRF1|0.0009632528810611<>ScoreDetail__7781|NFE2L1|0.000858132577546843__7996|NRF1|0.0009632528810611__ 0 0 0 0 0 12134 18464922 14359 6793 3471 ESRRA ERR ERR 26 0.3 factor-1 -2 (NRF-1,-2), NRF-1 -2 estrogen related receptor _amp_#x003b1 (ERR ERR _amp_#x003b1 and mitochondrial transcription factor A (Tfam) Tfam 70 1 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 20090 11057 SLC7A1 0 12135 18464922 14359 22024 11741 TFAM TFAM Tfam 34 0.9 _amp_#x003b1 (ERR ERR _amp_#x003b1 and mitochondrial transcription factor A (Tfam) Tfam 70 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12136 18464922 14361 19981 14929 SIRT1 SIRT1 SIRT1 8 0.3 Resveratrol has been shown to activate sirtuin 1 (SIRT1) SIRT1 and results in PPAR-_amp_#x003b3 -mediated transcriptional repression inhibition of adipogenesis 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12137 18464922 14361 17034 9236 PPARG PPAR PPAR-G 12 2.2 shown to activate sirtuin 1 (SIRT1) SIRT1 and results in PPAR-_amp_#x003b3 -mediated transcriptional repression inhibition of adipogenesis enhanced lipolysis and the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12138 18464922 14362 19981 14929 SIRT1 SIRT1 SIRT1 1 0.3 Activated SIRT1 leads to deactylation of PGC-1 _amp_#x003b1 resulting in an activation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12139 18464922 14362 17035 9237 PPARGC1A PGC1 PGC-1 6 1.2 Activated SIRT1 leads to deactylation of PGC-1 _amp_#x003b1 resulting in an activation of PGC-1 _amp_#x003b1 73 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12140 18464922 14362 17035 9237 PPARGC1A PGC1 PGC-1 13 1.2 to deactylation of PGC-1 _amp_#x003b1 resulting in an activation of PGC-1 _amp_#x003b1 73 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12141 18464922 14363 17035 9237 PPARGC1A PGC1 PGC-1 2 1.2 By deacetylating PGC-1 _amp_#x003b1 SIRT1 represses glycolysis increase hepatic glucose output and modulates 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12142 18464922 14363 19981 14929 SIRT1 SIRT1 SIRT1 5 0.3 By deacetylating PGC-1 _amp_#x003b1 SIRT1 represses glycolysis increase hepatic glucose output and modulates mitochondrial function 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12143 18464922 14364 17035 9237 PPARGC1A PGC1 PGC-1 0 1.2 PGC-1 _amp_#x003b1 is known as master regulator of mitochondrial biogenesis and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12144 18464922 14365 17034 9236 PPARG PPAR PPAR-G 1 2.2 Although PPAR-_amp_#x003b3 agonist treatments in R6/2 R6 2 failed it is premature 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12145 18464922 14365 17031 9232 PPARA PPAR PPARs 19 2.2 is premature to conclude that there is no role for PPARs in HD 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12146 18464922 14366 17034 9236 PPARG PPAR PPAR-G 13 2.2 in other models of HD are required to examine other PPAR-_amp_#x003b3 agonists 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12147 18464922 14367 17034 9236 PPARG PPAR PPAR-G 4 2.2 Moreover the effect of PPAR-_amp_#x003b3 agonists on the expression and activation of PGC-1 _amp_#x003b1 in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12148 18464922 14367 17035 9237 PPARGC1A PGC1 PGC-1 13 1.2 effect of PPAR-_amp_#x003b3 agonists on the expression and activation of PGC-1 _amp_#x003b1 in cell culture models of HD may provide preliminary 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12149 18464922 14368 17035 9237 PPARGC1A PGC1 PGC-1 11 1.2 rationale for that is based on the increasing evidence that PGC-1 _amp_#x003b1 expression which is downregulated in patients with Huntington's disease 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12150 18464922 14369 17035 9237 PPARGC1A PGC1 PGC-1 4 1.2 Thiazolidiones and rexinoids induce PGC-1 _amp_#x003b1 gene transcription in brown and white adipocytes 75 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12151 18464922 14370 17034 9236 PPARG PPAR PPAR-G 21 2.2 oxidation and adaptive thermoregulation then it can be predicted that PPAR-_amp_#x003b3 agonists could help HD mice to maintain thermoregulatory function when 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12152 18464922 14371 17035 9237 PPARGC1A PGC1 PGC-1 5 1.2 Based on the studies on PGC-1 _amp_#x003b1 knockout mice that shown to have neurodegenerative lesions particularly 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12153 18464922 14371 17035 9237 PPARGC1A PGC1 PGC-1 20 1.2 shown to have neurodegenerative lesions particularly in striatum suggest that PGC-1 _amp_#x003b1 may have an important function in neurons 76 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12154 18464922 14372 17035 9237 PPARGC1A PGC1 PGC-1 5 1.2 However the neurodegenerative lesions in PGC-1 _amp_#x003b1 knockout mice do not mimic lesions in HD 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12155 18464922 14373 17034 9236 PPARG PPAR PPAR-G 3 2.2 The role of PPAR-_amp_#x003b3 in ALS AD and Parkinson's disease are backed with evidence 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12156 18464922 14373 20996 11179 SOD1 ALS ALS 6 1.1 The role of PPAR-_amp_#x003b3 in ALS AD and Parkinson's disease are backed with evidence 19 20 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12157 18464922 14373 17034 9236 PPARG PPAR PPAR-G 28 2.2 with evidence 19 20 38 39 while the role of PPAR-_amp_#x003b3 in HD lacks critical evidence and needs to be studied 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12158 18464922 14374 17031 9232 PPARA PPAR PPARs 16 2.2 model of HD could shed light on the role of PPARs in HD 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12159 18464922 14375 17035 9237 PPARGC1A PGC1 PGC-1 16 1.2 mitochondrial biogenesis impairment in HD and potential neuroprotective role of PGC-1 _amp_#x003b1 in HD PPAR-_amp_#x003b3 desperately seeking further attention and these 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12160 18464922 14375 17034 9236 PPARG PPAR PPAR-G 20 2.2 HD and potential neuroprotective role of PGC-1 _amp_#x003b1 in HD PPAR-_amp_#x003b3 desperately seeking further attention and these types of studies could 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12161 18464922 14375 17034 9236 PPARG PPAR PPAR-G 39 2.2 of studies could provide essential data on the role of PPAR-_amp_#x003b3 in HD 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12162 18464922 14377 17034 9236 PPARG PPAR PPAR-G 5 2.2 Studies in patients treated with PPAR-_amp_#x003b3 agonists indicate that the reduction of insulin resistance is resulted 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12163 18464922 14377 17034 9236 PPARG PPAR PPAR-G 21 2.2 reduction of insulin resistance is resulted from the activation of PPAR-_amp_#x003b3 78 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12164 18464922 14378 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 's natural coactivator is PGC-1 _amp_#x003b1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12165 18464922 14378 17035 9237 PPARGC1A PGC1 PGC-1 6 1.2 PPAR-_amp_#x003b3 's natural coactivator is PGC-1 _amp_#x003b1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12166 18464922 14379 17035 9237 PPARGC1A PGC1 PGC-1 6 1.2 TZDs can mimic the effect of PGC-1 _amp_#x003b1 on PPAR-_amp_#x003b3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12167 18464922 14379 17034 9236 PPARG PPAR PPAR-G 9 2.2 TZDs can mimic the effect of PGC-1 _amp_#x003b1 on PPAR-_amp_#x003b3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12168 18464922 14380 17035 9237 PPARGC1A PGC1 PGC-1 1 1.2 If PGC-1 _amp_#x003b1 levels reduces or become inactivated by acetylation then the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12169 18464922 14380 17034 9236 PPARG PPAR PPAR-G 14 2.2 reduces or become inactivated by acetylation then the activity of PPAR-_amp_#x003b3 could be affected 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12170 18464922 14383 17034 9236 PPARG PPAR PPAR-G 8 2.2 In this review we highlighted the role of PPAR-_amp_#x003b3 in neurodegenerative diseases in particular in a mouse model of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12171 18464922 14383 20996 11179 SOD1 ALS ALS 20 1.1 in neurodegenerative diseases in particular in a mouse model of ALS and HD 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12172 18464922 14384 20996 11179 SOD1 ALS ALS 9 1.1 The utilization of pioglitazone in a mouse model of ALS by two independent studies provides strong indication for the involvement 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12173 18464922 14384 17034 9236 PPARG PPAR PPAR-G 21 2.2 two independent studies provides strong indication for the involvement of PPAR-_amp_#x003b3 in ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12174 18464922 14384 20996 11179 SOD1 ALS ALS 24 1.1 studies provides strong indication for the involvement of PPAR-_amp_#x003b3 in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12175 18464922 14385 17034 9236 PPARG PPAR PPAR-G 1 2.2 Whether PPAR-_amp_#x003b3 is involved in HD remains to be clarified as one 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12176 18464922 14385 17034 9236 PPARG PPAR PPAR-G 23 2.2 the treatment of R6/2 R6 2 mice with rosiglitazone another PPAR-_amp_#x003b3 agonist had no beneficial effect 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12177 18464922 14386 17034 9236 PPARG PPAR PPAR-G 10 2.2 In the future we will explore the mechanisms by which PPAR-_amp_#x003b3 agonists produce neuroprotection in a mouse model of ALS and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12178 18464922 14386 20996 11179 SOD1 ALS ALS 20 1.1 which PPAR-_amp_#x003b3 agonists produce neuroprotection in a mouse model of ALS and test whether PPAR-_amp_#x003b3 has a role in HD 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12179 18464922 14386 17034 9236 PPARG PPAR PPAR-G 24 2.2 neuroprotection in a mouse model of ALS and test whether PPAR-_amp_#x003b3 has a role in HD 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12180 18464922 14387 17034 9236 PPARG PPAR PPAR-G 12 2.2 be of great interest to determine whether the effect of PPAR-_amp_#x003b3 is powered by glial or neuronal cells or both in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12181 18464922 14388 17034 9236 PPARG PPAR PPAR-G 12 2.2 also be of great interest to determine the effect of PPAR-_amp_#x003b3 agonist on muscles in ALS and HD mouse models 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12182 18464922 14388 20996 11179 SOD1 ALS ALS 18 1.1 to determine the effect of PPAR-_amp_#x003b3 agonist on muscles in ALS and HD mouse models 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12183 18464922 14389 17034 9236 PPARG PPAR PPAR-G 17 2.2 cell culture studies are necessary in determining the role of PPAR-_amp_#x003b3 in ALS and HD 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12184 18464922 14389 20996 11179 SOD1 ALS ALS 20 1.1 studies are necessary in determining the role of PPAR-_amp_#x003b3 in ALS and HD 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12185 18464922 14390 17034 9236 PPARG PPAR PPAR-G 25 2.2 it would be very informative to test the effect of PPAR-_amp_#x003b3 agonists on HD mouse models for their effect in thermoregulation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12186 18464922 14391 17035 9237 PPARGC1A PGC1 PGC-1 3 1.2 The activation of PGC-1 _amp_#x003b1 in HD mouse models or overexpression of PGC-1 _amp_#x003b1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12187 18464922 14391 17035 9237 PPARGC1A PGC1 PGC-1 12 1.2 of PGC-1 _amp_#x003b1 in HD mouse models or overexpression of PGC-1 _amp_#x003b1 in HD mouse models show efficacy in blockage of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12188 18464922 14392 17035 9237 PPARGC1A PGC1 PGC-1 12 1.2 are confirmed then there is bonafide evidence that activation of PGC-1 _amp_#x003b1 could be a great therapeutic strategy for HD 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12189 18464922 14393 17035 9237 PPARGC1A PGC1 PGC-1 8 1.2 The lack of report on the role of PGC-1 _amp_#x003b1 in ALS is a limiting step on the hypothesis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12190 18464922 14393 20996 11179 SOD1 ALS ALS 11 1.1 lack of report on the role of PGC-1 _amp_#x003b1 in ALS is a limiting step on the hypothesis that PGC-1 _amp_#x003b1 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12191 18464922 14393 17035 9237 PPARGC1A PGC1 PGC-1 20 1.2 in ALS is a limiting step on the hypothesis that PGC-1 _amp_#x003b1 could be a target of investigation or therapeutic for 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12192 18464922 14393 20996 11179 SOD1 ALS ALS 31 1.1 _amp_#x003b1 could be a target of investigation or therapeutic for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12193 18464922 14394 20996 11179 SOD1 ALS ALS 5 1.1 Mitochondria have been implicated in ALS and PGC-1 _amp_#x003b1 has possible role in mitochondrial biogenesis therefore 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12194 18464922 14394 17035 9237 PPARGC1A PGC1 PGC-1 7 1.2 Mitochondria have been implicated in ALS and PGC-1 _amp_#x003b1 has possible role in mitochondrial biogenesis therefore it would 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12195 18464922 14394 17035 9237 PPARGC1A PGC1 PGC-1 25 1.2 therefore it would be informative to examine mitochondrial abnormalities and PGC-1 _amp_#x003b1 in ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12196 18464922 14394 20996 11179 SOD1 ALS ALS 28 1.1 be informative to examine mitochondrial abnormalities and PGC-1 _amp_#x003b1 in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12197 18464922 14395 17034 9236 PPARG PPAR PPAR-G 2 2.2 However since PPAR-_amp_#x003b3 agonist shown to activate PGC-1 _amp_#x003b1 therefore there is an 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12198 18464922 14395 17035 9237 PPARGC1A PGC1 PGC-1 8 1.2 However since PPAR-_amp_#x003b3 agonist shown to activate PGC-1 _amp_#x003b1 therefore there is an indirect possibility that PGC-1 _amp_#x003b1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12199 18464922 14395 17035 9237 PPARGC1A PGC1 PGC-1 18 1.2 activate PGC-1 _amp_#x003b1 therefore there is an indirect possibility that PGC-1 _amp_#x003b1 in connection with PPAR-_amp_#x003b3 could play some role in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12200 18464922 14395 17034 9236 PPARG PPAR PPAR-G 23 2.2 is an indirect possibility that PGC-1 _amp_#x003b1 in connection with PPAR-_amp_#x003b3 could play some role in ALS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12201 18464922 14395 20996 11179 SOD1 ALS ALS 30 1.1 _amp_#x003b1 in connection with PPAR-_amp_#x003b3 could play some role in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000878787222981725<>ScoreDetail__5468|IGFALS|0.000465213801779607__11179|SOD1|0.000878787222981725__ 0 0 0 0 0 12278 18464925 14398 17034 9236 PPARG PPAR PPAR-G 10 2.2 Abstract In the recent years the peroxisome proliferator-activated receptor-_amp_#x003b3 PPAR-_amp_#x003b3 a well known target for type II diabetes treatment has 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12279 18464925 14399 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 agonists which include naturally occurring compounds (such such as long 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12280 18464925 14400 17034 9236 PPARG PPAR PPAR-G 4 2.2 The pleiotropic effects of PPAR-_amp_#x003b3 agonists are likely to be mediated by several mechanisms involving 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12281 18464925 14401 17034 9236 PPARG PPAR PPAR-G 15 2.2 will review the recent findings supporting a major role for PPAR-_amp_#x003b3 agonists in controlling neuroinflammation and neurodegeneration through their activities on 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12282 18464925 14404 17034 9236 PPARG PPAR PPAR-G 5 2.2 The peroxisome proliferator-activated receptor-_amp_#x003b3 PPAR-_amp_#x003b3 belongs to the hormone nuclear receptor super family 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12283 18464925 14406 17034 9236 PPARG PPAR PPAR-G 15 2.2 the regulation of genes involved in lipid and carbohydrate metabolism PPAR-_amp_#x003b3 and the other two isoforms PPAR-_amp_#x003b1 and _amp_#x003b4 deeply affect 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12284 18464925 14406 17031 9232 PPARA PPAR PPAR-A 22 2.2 lipid and carbohydrate metabolism PPAR-_amp_#x003b3 and the other two isoforms PPAR-_amp_#x003b1 and _amp_#x003b4 deeply affect lipid homeostasis and insulin sensitivity 1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12285 18464925 14408 17034 9236 PPARG PPAR PPAR-G 16 2.2 accumulating evidence suggests that besides diabetes and metabolic syndrome 4 PPAR-_amp_#x003b3 agonists have significant therapeutic potential in brain disorders 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12286 18464925 14409 17034 9236 PPARG PPAR PPAR-G 13 2.2 of experimental studies and few clinical observations have suggested that PPAR-_amp_#x003b3 ligands may be successfully exploited to treat a wide range 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12287 18464925 14411 9947 5468 IGFALS ALS ALS 4 0.3 In amyotrophic lateral sclerosis (ALS) ALS and Parkinson's disease animal models the TZD pioglitazone ameliorated the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00050067446478045<>ScoreDetail__5468|IGFALS|0.000328025032588574__11179|SOD1|0.00050067446478045__ 0 0 0 0 0 12288 18464925 14415 17034 9236 PPARG PPAR PPAR-G 16 2.2 well known model for autoimmune demyelinating diseases synthetic and natural PPAR-_amp_#x003b3 ligands_amp_#x02014 as well as some PPAR-_amp_#x003b1 or _amp_#x003b4 agonists_amp_#x02014 have 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12289 18464925 14415 17031 9232 PPARA PPAR PPAR-A 22 2.2 diseases synthetic and natural PPAR-_amp_#x003b3 ligands_amp_#x02014 as well as some PPAR-_amp_#x003b1 or _amp_#x003b4 agonists_amp_#x02014 have been reported to ameliorate clinical symptoms 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12290 18464925 14416 17034 9236 PPARG PPAR PPAR-G 14 2.2 obtained in experimental models of ocular diseases have evidenced that PPAR-_amp_#x003b3 could be targeted to control inflammation and treat invalidating diseases 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12291 18464925 14417 17031 9232 PPARA PPAR PPAR 13 2.8 of the amount of data on the therapeutic activities of PPAR agonists in EAE clinical studies are still lacking and reports 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12292 18464925 14419 17034 9236 PPARG PPAR PPAR-G 4 2.2 The beneficial effects of PPAR-_amp_#x003b3 agonists in degenerative inflammatory and traumatic brain pathologies are most 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12293 18464925 14420 17034 9236 PPARG PPAR PPAR-G 2 2.2 Besides microglia PPAR-_amp_#x003b3 agonists can act on other neural cell types including astrocytes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12294 18464925 14423 17034 9236 PPARG PPAR PPAR-G 6 2.2 Several of the beneficial effects of PPAR-_amp_#x003b3 result from its ability once activated by specific ligand to 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12295 18464925 14424 17034 9236 PPARG PPAR PPAR-G 3 2.2 In addition some PPAR-_amp_#x003b3 ligands may exert specific activities independently from PPAR-_amp_#x003b3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12296 18464925 14424 17034 9236 PPARG PPAR PPAR-G 12 2.2 addition some PPAR-_amp_#x003b3 ligands may exert specific activities independently from PPAR-_amp_#x003b3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12297 18464925 14425 4409 30880 CISD1 mitoNEET mitoneet 37 1.8 I of the respiratory chain and the newly described protein mitoneet 29 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12298 18464925 14429 17034 9236 PPARG PPAR PPAR-G 5 2.2 Figure 1 Cellular targets of PPAR-_amp_#x003b3 agonists in neurodegenerative diseases 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12299 18464925 14430 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 agonists can control neuroinflammation neurodegeneration and demyelination by effecting several 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12300 18464925 14432 17034 9236 PPARG PPAR PPAR-G 2 2.2 Figure 2 PPAR-_amp_#x003b3 expression in culture rat oligodendrocytes and in white matter (postnatal 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12301 18464925 14433 17034 9236 PPARG PPAR PPAR-G 15 2.2 rat OL progenitor cultures prepared as previously described 40 for PPAR-_amp_#x003b3 (more more ... 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12302 18464925 14437 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 STRUCTURE FUNCTIONS AND AGONISTS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12303 18464925 14438 17034 9236 PPARG PPAR PPAR-G 1 2.2 The PPAR-_amp_#x003b3 and the two closely related PPAR-_amp_#x003b1 and PPAR-_amp_#x003b4 (also also 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12304 18464925 14438 17031 9232 PPARA PPAR PPAR-A 8 2.2 The PPAR-_amp_#x003b3 and the two closely related PPAR-_amp_#x003b1 and PPAR-_amp_#x003b4 (also also known as _amp_#x003b2 NUC-1 or FAAR 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12305 18464925 14438 17034 9236 PPARG PPAR PPAR-G 11 2.2 The PPAR-_amp_#x003b3 and the two closely related PPAR-_amp_#x003b1 and PPAR-_amp_#x003b4 (also also known as _amp_#x003b2 NUC-1 or FAAR share a 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 17033 9235 PPARD 0 12306 18464925 14438 17033 9235 PPARD NUC1 NUC-1 18 2.7 closely related PPAR-_amp_#x003b1 and PPAR-_amp_#x003b4 (also also known as _amp_#x003b2 NUC-1 or FAAR share a high homology but differ for tissue 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12307 18464925 14438 17033 9235 PPARD FAAR FAAR 20 2.7 PPAR-_amp_#x003b1 and PPAR-_amp_#x003b4 (also also known as _amp_#x003b2 NUC-1 or FAAR share a high homology but differ for tissue distribution and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12308 18464925 14439 17031 9232 PPARA PPAR PPAR-A 0 2.2 PPAR-_amp_#x003b1 is mainly expressed in tissues with high catabolic rates of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12309 18464925 14439 17034 9236 PPARG PPAR PPAR-G 22 2.2 fatty acids such as the liver muscle and heart whereas PPAR-_amp_#x003b4 shows a much wider distribution 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 17033 9235 PPARD 0 12310 18464925 14440 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 is highly expressed in adipose tissue and in cells of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12311 18464925 14441 17034 9236 PPARG PPAR PPAR-G 3 2.2 In the brain PPAR-_amp_#x003b3 is expressed in several cell types including microglia astrocytes oligodendrocytes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12312 18464925 14442 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 protein shows a remarkable conservation across species 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12313 18464925 14443 17034 9236 PPARG PPAR PPAR-G 4 2.2 Human and the murine PPAR-_amp_#x003b3 proteins show 95% identity at the amino acid level 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12314 18464925 14444 17034 9236 PPARG PPAR PPAR-G 2 2.2 The human PPAR-_amp_#x003b3 gene is located on chromosome 3 and generates at least 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12315 18464925 14444 17034 9236 PPARG PPAR PPAR-G 17 2.2 on chromosome 3 and generates at least three mRNA transcripts PPAR-_amp_#x003b3 1 PPAR-_amp_#x003b3 2 and PPAR-_amp_#x003b3 3 30 _amp_#x02013 32 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12316 18464925 14444 17034 9236 PPARG PPAR PPAR-G 20 2.2 3 and generates at least three mRNA transcripts PPAR-_amp_#x003b3 1 PPAR-_amp_#x003b3 2 and PPAR-_amp_#x003b3 3 30 _amp_#x02013 32 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12317 18464925 14444 17034 9236 PPARG PPAR PPAR-G 24 2.2 at least three mRNA transcripts PPAR-_amp_#x003b3 1 PPAR-_amp_#x003b3 2 and PPAR-_amp_#x003b3 3 30 _amp_#x02013 32 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12318 18464925 14445 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 1 e PPAR-_amp_#x003b3 3 mRNAs encode for the same protein 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12319 18464925 14445 17034 9236 PPARG PPAR PPAR-G 4 2.2 PPAR-_amp_#x003b3 1 e PPAR-_amp_#x003b3 3 mRNAs encode for the same protein while PPAR-_amp_#x003b3 2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12320 18464925 14445 17034 9236 PPARG PPAR PPAR-G 14 2.2 e PPAR-_amp_#x003b3 3 mRNAs encode for the same protein while PPAR-_amp_#x003b3 2 mRNA gives rise to a protein containing 28 additional 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12321 18464925 14446 17031 9232 PPARA PPAR PPARs 5 2.2 At protein level all three PPARs show a similar organization in five different functional domains two 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12322 18464925 14449 17031 9232 PPARA PPAR PPARs 20 2.2 hydrophobic domains of the ligand explains the low ligand-specificity of PPARs 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12323 18464925 14450 17031 9232 PPARA PPAR PPAR 6 2.8 Nonetheless the LBDs of the three PPAR isotypes have sufficiently divergent amino acid sequences to allow some 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12324 18464925 14451 17031 9232 PPARA PPAR PPAR 8 2.8 Several unsaturated fatty acids bind to all three PPAR isoforms whereas saturated fatty acids are in general poor PPAR 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12325 18464925 14451 17031 9232 PPARA PPAR PPAR 18 2.8 PPAR isoforms whereas saturated fatty acids are in general poor PPAR ligands 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12326 18464925 14452 17031 9232 PPARA PPAR PPAR 10 2.8 However given the relatively high concentration of lipids required for PPAR activation (in in the micromolar or submicromolar concentration range their 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12327 18464925 14452 17031 9232 PPARA PPAR PPAR 24 2.8 or submicromolar concentration range their _amp_#x0201c in vivo_amp_#x0201d role as PPAR ligands remains a controversial issue 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12328 18464925 14453 17034 9236 PPARG PPAR PPAR-G 7 2.2 Some arachidonic acid metabolites are more effective PPAR-_amp_#x003b3 ligands than the precursor 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12329 18464925 14454 17034 9236 PPARG PPAR PPAR-G 21 2.2 _amp_#x003b2 -unsaturated ketone in the cyclopentenone ring was the first PPAR-_amp_#x003b3 endogenous ligand described in 1995 by two independent groups 33 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12330 18464925 14455 17034 9236 PPARG PPAR PPAR-G 3 2.2 The implication of PPAR-_amp_#x003b3 in several important metabolic and degenerative disorders has strongly pushed 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12331 18464925 14455 17034 9236 PPARG PPAR PPAR-G 19 2.2 and degenerative disorders has strongly pushed the research of specific PPAR-_amp_#x003b3 agonists and antagonist (for for review see 35 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12332 18464925 14456 17034 9236 PPARG PPAR PPAR-G 5 2.2 A major group of synthetic PPAR-_amp_#x003b3 agonists is represented by the antidiabetic drugs TZDs originally identified 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12333 18464925 14458 17034 9236 PPARG PPAR PPAR-G 5 2.2 A different series of synthetic PPAR-_amp_#x003b3 ligands are derived by L-tyrosine GI262570 GW1929 and GW7845 which 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12334 18464925 14458 17034 9236 PPARG PPAR PPAR-G 27 2.2 were developed on the basis of their activity on human PPAR-_amp_#x003b3 and are among the most potent PPAR-_amp_#x003b3 agonists being active 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12335 18464925 14458 17034 9236 PPARG PPAR PPAR-G 35 2.2 activity on human PPAR-_amp_#x003b3 and are among the most potent PPAR-_amp_#x003b3 agonists being active at low nanomolar concentrations 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12336 18464925 14459 17031 9232 PPARA PPAR PPARs 20 2.2 the heterogeneous NSAID family have been described as agonists for PPARs 35 and reference therein 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12337 18464925 14460 17034 9236 PPARG PPAR PPAR-G 7 2.2 In most cases the doses required for PPAR-_amp_#x003b3 agonist activity are in the high micromolar range thus largely 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12338 18464925 14460 4829 2294 COX8A COX COXs 28 0.0 exceeding those required for in vivo inhibition of cyclooxygenases (COXs), COXs the main target of these drugs 13 JUMiner_v2.2 1 1 cox; 0 1 0 TotalCon:2<>2294|COX8A|1351|No_GeneRif__2267|COX5A|9377|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 12339 18464925 14461 17031 9232 PPARA PPAR PPAR 15 2.8 or paracetamol lack of agonistic activity for any of the PPAR subtypes whereas indomethacin ibuprofen and diclofenac are selective for the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12340 18464925 14462 17034 9236 PPARG PPAR PPAR-G 22 2.2 flurbiprofen HCT1026 and NXC 2216 were both able to activate PPAR-_amp_#x003b3 and induce its specific binding to a PPRE sequence 36 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12341 18464925 14466 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 AGONISTS AND OLIGODENDROCYTE BIOLOGY 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12342 18464925 14475 17031 9232 PPARA PPAR PPARs 4 2.2 Given the role of PPARs in lipid metabolism it is conceivable that this group of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12343 18464925 14476 17033 9235 PPARD PPAR PPAR-B 1 2.2 Although PPAR-_amp_#x003b2 / _amp_#x003b4 has been long considered the PPAR type mainly 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12344 18464925 14476 17031 9232 PPARA PPAR PPAR 10 2.8 Although PPAR-_amp_#x003b2 / _amp_#x003b4 has been long considered the PPAR type mainly expressed in OLs and involved in myelination 43 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12345 18464925 14476 17034 9236 PPARG PPAR PPAR-G 32 2.2 myelination 43 44 recent findings support an important role for PPAR-_amp_#x003b3 activators in OL protection and differentiation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12346 18464925 14477 17034 9236 PPARG PPAR PPAR-G 7 2.2 The first evidence for a role of PPAR-_amp_#x003b3 in OL differentiation was reported by Roth et al 45 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12347 18464925 14478 17031 9232 PPARA PPAR PPAR 25 2.8 the authors first demonstrated that these cells expressed all three PPAR isoforms and found that natural and synthetic PPAR-_amp_#x003b3 agonists but 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12348 18464925 14478 17034 9236 PPARG PPAR PPAR-G 33 2.2 all three PPAR isoforms and found that natural and synthetic PPAR-_amp_#x003b3 agonists but not other isoform activators enhance process extension and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12349 18464925 14479 17034 9236 PPARG PPAR PPAR-G 6 2.2 These effects were blocked by the PPAR-_amp_#x003b3 antagonist GW9662 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12350 18464925 14480 446 327 AGPS ADAPS ADAPS 13 0.3 was accompanied by enhanced expression of alkyl-dihydroxyacetone phosphate synthase (ADAPS), ADAPS a peroxisomal enzyme required for the synthesis of plasmalogen an 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12351 18464925 14481 17034 9236 PPARG PPAR PPAR-G 4 2.2 These observations suggest that PPAR-_amp_#x003b3 mediated mechanisms may be important for OL differentiation and peroxisome 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12352 18464925 14483 17034 9236 PPARG PPAR PPAR-G 7 2.2 In line with the proposed role of PPAR-_amp_#x003b3 in controlling OL differentiation and functions we have recently confirmed 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12353 18464925 14483 17034 9236 PPARG PPAR PPAR-G 22 2.2 differentiation and functions we have recently confirmed the expression of PPAR-_amp_#x003b3 in highly purified rat OL cultures ( Figure 2 (a)) 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12354 18464925 14485 17034 9236 PPARG PPAR PPAR-G 8 2.2 In addition we found an increased expression of PPAR-_amp_#x003b3 in white matter of young rats (post post natal day 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12355 18464925 14486 12436 6925 MBP MBP MBP 52 1.9 indicated by the strong reduction of myelin basic protein (MBP) MBP expression ( Figure 2 (b)) b 1 JUMiner_v2.2 1 0 0 2 6925 TotalCon:3<>6925|MBP|4155|Complete__9362|PRG2|5553|Complete__6922|MBL2|4153|Complete__<>AvaiableGeneRif=3<>BEST:6925|MBP|0.000578191417246852<>ScoreDetail__6925|MBP|0.000578191417246852__9362|PRG2|0.000576397030089879__6922|MBL2|0.00025948088542688__ 0 0 0 0 0 12356 18464925 14487 17034 9236 PPARG PPAR PPAR-G 1 2.2 Whether PPAR-_amp_#x003b3 over-expression is part of an adaptive response to the hypoxic 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12357 18464925 14489 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 AGONISTS AND OLIGODENDROCYTE BIOLOGY 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12358 18464925 14490 17034 9236 PPARG PPAR PPAR-G 16 2.2 the above findings Xiang et al 49 reported that the PPAR-_amp_#x003b3 natural ligand 15d-PGJ 2 but not other PGs induced apoptosis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12359 18464925 14492 17034 9236 PPARG PPAR PPAR-G 20 2.2 cultures 50 cell death was independent of the nuclear receptor PPAR-_amp_#x003b3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12360 18464925 14495 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 AGONISTS AND ASTROCYTES 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12361 18464925 14498 14639 7968 NR1I2 PRR PRRs 20 0.6 they express several_amp_#x02014 though fewer than microglia_amp_#x02014 pattern-recognition receptors (PRRs) PRRs such as for example the Toll-like receptors and release cytokines 13 JUMiner_v2.2 1 2 UserEdit 0 2 7968 TotalCon:2<>9706|PVRL1|5818|Complete__7968|NR1I2|8856|Complete__<>AvaiableGeneRif=2<>BEST:7968|NR1I2|0.000541958385455212<>ScoreDetail__7968|NR1I2|0.000541958385455212__9706|PVRL1|0.000392674626390011__ 1 1 0 0 0 12362 18464925 14500 8254 4235 GFAP GFAP GFAP 13 2.5 characterized by increased expression of glial fibrillary acidic protein (GFAP), GFAP a constituent of the intermediate filaments are typical of most 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12363 18464925 14502 17034 9236 PPARG PPAR PPAR-G 2 2.2 Astrocytes express PPAR-_amp_#x003b3 53 54 and accumulating evidence over the last ten years 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12364 18464925 14502 17034 9236 PPARG PPAR PPAR-G 19 2.2 and accumulating evidence over the last ten years indicates that PPAR-_amp_#x003b3 agonists modulate astrocyte functions 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12365 18464925 14503 17034 9236 PPARG PPAR PPAR-G 27 2.2 in time- and dose-dependent manners through a mechanism independent of PPAR-_amp_#x003b3 and involving cAMP/PKA cAMP PKA signaling 55 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12366 18464925 14504 20023 11005 SLC2A1 GLUT1 GLUT-1 10 2.3 Pioglitazone did not modify the expression of the glucose transporter GLUT-1 which is mainly expressed in glial and endothelial cells but 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12367 18464925 14504 20023 11005 SLC2A1 GLUT1 GLUT-1 28 2.3 endothelial cells but rather it increased glucose flux through pre-existing GLUT-1 protein 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12368 18464925 14508 20023 11005 SLC2A1 GLUT1 GLUT-1 13 2.3 intracellular glucose levels are replenished by glucose transport through the GLUT-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12369 18464925 14512 17034 9236 PPARG PPAR PPAR-G 5 2.2 Another important mechanism by which PPAR-_amp_#x003b3 agonists could exert neuroprotection by influencing astrocyte functions is the 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12370 18464925 14513 17034 9236 PPARG PPAR PPAR-G 9 2.2 Romera et al 56 reported that the PPAR-_amp_#x003b3 antagonists T0070907 prevented the ischemic preconditioning-induced (IPC) IPC neuroprotection in 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12371 18464925 14514 20017 10940 SLC1A2 GLT-1 GLT-1 15 2.8 agonist L-796 449 induced a concentration-dependent increase in glutamate transporter GLT-1 expression and 3 H glutamate uptake in rat astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12372 18464925 14515 20017 10940 SLC1A2 GLT1 GLT1 13 3.1 identified six putative PPREs in the promoter region of GLT1/EAAT2 GLT1 EAAT2 gene suggesting GLT1/EAAT2 GLT1 EAAT2 glutamate transporter is a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12373 18464925 14515 20017 10940 SLC1A2 EAAT2 EAAT2 13 3.3 six putative PPREs in the promoter region of GLT1/EAAT2 GLT1 EAAT2 gene suggesting GLT1/EAAT2 GLT1 EAAT2 glutamate transporter is a novel 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12374 18464925 14515 20017 10940 SLC1A2 GLT1 GLT1 16 3.1 the promoter region of GLT1/EAAT2 GLT1 EAAT2 gene suggesting GLT1/EAAT2 GLT1 EAAT2 glutamate transporter is a novel PPAR-_amp_#x003b3 target gene 56 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12375 18464925 14515 20017 10940 SLC1A2 EAAT2 EAAT2 16 3.3 promoter region of GLT1/EAAT2 GLT1 EAAT2 gene suggesting GLT1/EAAT2 GLT1 EAAT2 glutamate transporter is a novel PPAR-_amp_#x003b3 target gene 56 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12376 18464925 14515 17034 9236 PPARG PPAR PPAR-G 22 2.2 gene suggesting GLT1/EAAT2 GLT1 EAAT2 glutamate transporter is a novel PPAR-_amp_#x003b3 target gene 56 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12377 18464925 14516 14373 7808 NGF NGF NGF 15 1.2 synthesis and release of neurotrophic factor nerve growth factor (NGF) NGF in mouse primary astrocytes which could further contribute to neuroprotection 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12378 18464925 14518 17034 9236 PPARG PPAR PPAR-G 10 2.2 Such neurotoxic activities have been shown to be reduced by PPAR-_amp_#x003b3 agonists in several experimental paradigms 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12379 18464925 14519 10463 6018 IL6 IL-6 IL-6 17 1.6 reported to inhibit the production of nitric oxide (NO), NO IL-6 and TNF-_amp_#x003b1 as well as expression of the inducible enzymes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12380 18464925 14519 22551 11892 TNF TNF TNF-A 19 0.3 inhibit the production of nitric oxide (NO), NO IL-6 and TNF-_amp_#x003b1 as well as expression of the inducible enzymes iNOS and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12381 18464925 14519 14535 7873 NOS2A iNOS iNOS 29 2.2 and TNF-_amp_#x003b1 as well as expression of the inducible enzymes iNOS and COX2 induced in LPS-stimulated astrocyte and microglial cultures 58 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12382 18464925 14519 17610 9605 PTGS2 COX2 COX2 31 2.5 as well as expression of the inducible enzymes iNOS and COX2 induced in LPS-stimulated astrocyte and microglial cultures 58 1 JUMiner_v2.2 1 0 0 2 9605 TotalCon:2<>7421|MT-CO2|4513|Complete__9605|PTGS2|5743|Complete__<>AvaiableGeneRif=2<>BEST:9605|PTGS2|0.000741811477344508<>ScoreDetail__7421|MT-CO2|0.000345376095109766__9605|PTGS2|0.000741811477344508__ 0 0 0 0 0 12383 18464925 14519 10676 6121 IRF6 LPS LPS-stimulated 34 0.3 expression of the inducible enzymes iNOS and COX2 induced in LPS-stimulated astrocyte and microglial cultures 58 11 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 12384 18464925 14521 17034 9236 PPARG PPAR PPAR-G 14 2.2 in vivo effects were substantially attenuated by cotreatment with the PPAR-_amp_#x003b3 antagonist GW9662 supporting the involvement of PPAR-_amp_#x003b3 activation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12385 18464925 14521 17034 9236 PPARG PPAR PPAR-G 22 2.2 cotreatment with the PPAR-_amp_#x003b3 antagonist GW9662 supporting the involvement of PPAR-_amp_#x003b3 activation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12386 18464925 14522 10437 5992 IL1B IL-1 IL-1 14 1.3 above described TZDs the natural ligand 15d-PGJ 2 prevented the IL-1 _amp_#x003b2 -induced COX-2 mRNA accumulation in human astrocytes through a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12387 18464925 14522 17610 9605 PTGS2 COX-2 COX-2 17 3.0 the natural ligand 15d-PGJ 2 prevented the IL-1 _amp_#x003b2 -induced COX-2 mRNA accumulation in human astrocytes through a PPAR _amp_#x003b3 -independent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12388 18464925 14522 17031 9232 PPARA PPAR PPAR 25 2.8 _amp_#x003b2 -induced COX-2 mRNA accumulation in human astrocytes through a PPAR _amp_#x003b3 -independent mechanism 60 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12389 18464925 14523 12337 6871 MAPK1 MAP MAP 15 2.2 colleagues 61 showed that ciglitazone and 15d-PGJ 2 activated the MAP kinase cascades (Erk, Erk Jnk and p38 MAP kinase in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12390 18464925 14523 12349 6881 MAPK8 JNK Jnk 19 1.2 and 15d-PGJ 2 activated the MAP kinase cascades (Erk, Erk Jnk and p38 MAP kinase in astrocytes by a PPAR-_amp_#x003b3 independent 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12391 18464925 14523 12337 6871 MAPK1 p38 p38 21 2.2 2 activated the MAP kinase cascades (Erk, Erk Jnk and p38 MAP kinase in astrocytes by a PPAR-_amp_#x003b3 independent mechanism which 1 JUMiner_v2.2 1 0 0 2 6871 TotalCon:4<>1189|AHSA1|10598|Complete__6876|MAPK14|1432|Complete__6871|MAPK1|5594|Complete__6878|MAPK4|5596|Complete__<>AvaiableGeneRif=4<>BEST:6871|MAPK1|0.000950812361999151<>ScoreDetail__1189|AHSA1|0.00031262211801485__6878|MAPK4|0.00073131245464188__6871|MAPK1|0.000950812361999151__6876|MAPK14|0.000714044604677286__ 0 0 0 0 0 12392 18464925 14523 12337 6871 MAPK1 MAP MAP 22 2.2 activated the MAP kinase cascades (Erk, Erk Jnk and p38 MAP kinase in astrocytes by a PPAR-_amp_#x003b3 independent mechanism which required 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12393 18464925 14523 17034 9236 PPARG PPAR PPAR-G 28 2.2 Erk Jnk and p38 MAP kinase in astrocytes by a PPAR-_amp_#x003b3 independent mechanism which required the presence of ROS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12394 18464925 14523 18723 10261 ROS1 ROS ROS 37 0.0 by a PPAR-_amp_#x003b3 independent mechanism which required the presence of ROS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12395 18464925 14524 17034 9236 PPARG PPAR PPAR-G 3 2.2 Again independently of PPAR-_amp_#x003b3 15d-PGJ 2 and rosiglitazone reduced the phosphorylation of signal transducers 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12396 18464925 14524 21414 11362 STAT1 STAT STAT 20 1.2 the phosphorylation of signal transducers and activators of transcription (STAT) STAT 1 and 3 as well as Janus kinase 1 (JAK1) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12397 18464925 14524 10781 6190 JAK1 JAK1 JAK1 30 1.2 1 and 3 as well as Janus kinase 1 (JAK1) JAK1 and JAK2 in activated astrocytes and microglia 62 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12398 18464925 14524 10782 6192 JAK2 JAK2 JAK2 30 0.9 1 and 3 as well as Janus kinase 1 (JAK1) JAK1 and JAK2 in activated astrocytes and microglia 62 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12399 18464925 14524 10782 6192 JAK2 JAK2 JAK2 32 0.9 3 as well as Janus kinase 1 (JAK1) JAK1 and JAK2 in activated astrocytes and microglia 62 15 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12400 18464925 14525 17031 9232 PPARA PPAR PPAR-ligands 15 2.2 Drew 63 extended the analysis of the anti-inflammatory activity of PPAR-ligands to other inflammatory mediators belonging to the IL-12 family of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12401 18464925 14526 10676 6121 IRF6 LPS LPS 6 0.3 They found that in primary astrocytes LPS induced the production of IL-12p40 IL-23 and IL-27p28 proteins which 11 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 12402 18464925 14526 10521 15488 IL23A IL-23 IL-23 12 1.3 that in primary astrocytes LPS induced the production of IL-12p40 IL-23 and IL-27p28 proteins which was significantly reduced in the presence 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12403 18464925 14526 10526 19157 IL27 IL27p28 IL-27p28 14 0.8 primary astrocytes LPS induced the production of IL-12p40 IL-23 and IL-27p28 proteins which was significantly reduced in the presence of 15d-PGJ 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12404 18464925 14527 17034 9236 PPARG PPAR PPAR-G 36 2.2 multiple sclerosis this observation further support the potential role of PPAR-_amp_#x003b3 agonists in MS treatment 5 64 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12405 18464925 14528 17034 9236 PPARG PPAR PPAR-G 7 2.2 In line with the beneficial effect of PPAR-_amp_#x003b3 agonists in experimental models of inflammatory diseases PPAR-_amp_#x003b3 has also 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12406 18464925 14528 17034 9236 PPARG PPAR PPAR-G 16 2.2 effect of PPAR-_amp_#x003b3 agonists in experimental models of inflammatory diseases PPAR-_amp_#x003b3 has also been involved in anti-inflammatory functions of IL-4 a 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12407 18464925 14528 10458 6014 IL4 IL-4 IL-4 26 1.3 diseases PPAR-_amp_#x003b3 has also been involved in anti-inflammatory functions of IL-4 a Th2 type cytokine which plays an important role in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12408 18464925 14528 22088 15934 TH1L TH1 Th1 38 0.0 Th2 type cytokine which plays an important role in controlling Th1 cell responses and resolution of inflammation 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12409 18464925 14529 14535 7873 NOS2A iNOS iNOS 11 2.2 Paintlia et al 65 demonstrated that the inhibition of iNOS expression and the increase of survival of differentiating OPs induced 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12410 18464925 14529 10458 6014 IL4 IL-4 IL-4 23 1.3 and the increase of survival of differentiating OPs induced by IL-4 in inflammatory cytokine-stimulated mixed cultures are mediated by PPAR-_amp_#x003b3 activation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12411 18464925 14529 17034 9236 PPARG PPAR PPAR-G 32 2.2 by IL-4 in inflammatory cytokine-stimulated mixed cultures are mediated by PPAR-_amp_#x003b3 activation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12412 18464925 14530 17034 9236 PPARG PPAR PPAR-G 16 2.2 authors describe a coordinate increase in the expression of both PPAR-_amp_#x003b3 and its natural ligand-producing enzyme 12/15-lipoxygenase 12 15-lipoxygenase (12/15-LOX) 12 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12413 18464925 14530 10458 6014 IL4 IL-4 IL-4-induced 32 1.3 (12/15-LOX) 12 15-LOX in IL-4-treated glial cells and show that IL-4-induced PPAR-_amp_#x003b3 activation antagonizes NF-_amp_#x003ba B transactivation in inflammatory cytokine-stimulated astrocytes 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12414 18464925 14530 17034 9236 PPARG PPAR PPAR-G 33 2.2 12 15-LOX in IL-4-treated glial cells and show that IL-4-induced PPAR-_amp_#x003b3 activation antagonizes NF-_amp_#x003ba B transactivation in inflammatory cytokine-stimulated astrocytes 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12415 18464925 14531 17034 9236 PPARG PPAR PPAR-G 4 2.2 A similar upregulation of PPAR-_amp_#x003b3 by IL-4 was demonstrated in cultured microglial cells 66 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12416 18464925 14531 10458 6014 IL4 IL-4 IL-4 7 1.3 A similar upregulation of PPAR-_amp_#x003b3 by IL-4 was demonstrated in cultured microglial cells 66 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12417 18464925 14532 10458 6014 IL4 IL-4 IL-4 3 1.3 To link between IL-4 and PPAR-_amp_#x003b3 is completed by the observation that the anti-inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12418 18464925 14532 17034 9236 PPARG PPAR PPAR-G 5 2.2 To link between IL-4 and PPAR-_amp_#x003b3 is completed by the observation that the anti-inflammatory activity of 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12419 18464925 14532 10458 6014 IL4 IL-4 IL-4 27 1.3 the TZD troglitazone was mediated by its ability to increase IL-4 expression in glial cultures 67 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12420 18464925 14534 10437 5992 IL1B IL-1 IL-1 12 1.3 recent study 15d-PGJ 2 and ciglitazone suppress the production of IL-1 _amp_#x003b2 and NO in Staphylococcus aureus-stimulated astrocytes 68 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12421 18464925 14535 22217 11848 TLR2 TLR2 TLR2 4 0.3 Interestingly 15d-PGJ 2 attenuated TLR2 expression the PPR recognizing Staphylococcus aureus 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12422 18464925 14536 17034 9236 PPARG PPAR PPAR-G 20 2.2 the release of proinflammatory mediators induced by Staphylococcus aureus in PPAR-_amp_#x003b3 -deficient astrocytes supporting PPAR-_amp_#x003b3 -independent effects of these compounds 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12423 18464925 14536 17034 9236 PPARG PPAR PPAR-G 25 2.2 mediators induced by Staphylococcus aureus in PPAR-_amp_#x003b3 -deficient astrocytes supporting PPAR-_amp_#x003b3 -independent effects of these compounds 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12424 18464925 14538 8254 4235 GFAP GFAP GFAP 5 2.5 At noncytotoxic concentrations OTA down-regulated GFAP expression while it upregulated vimentin 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12425 18464925 14539 17034 9236 PPARG PPAR PPAR-G 3 2.2 Interestingly OTA increased PPAR-_amp_#x003b3 expression possibly increasing the susceptibility of OTA-exposed cells to PPAR-_amp_#x003b3 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12426 18464925 14539 17034 9236 PPARG PPAR PPAR-G 14 2.2 PPAR-_amp_#x003b3 expression possibly increasing the susceptibility of OTA-exposed cells to PPAR-_amp_#x003b3 agonist treatment 69 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12427 18464925 14541 17034 9236 PPARG PPAR PPAR-G 0 2.2 PPAR-_amp_#x003b3 AGONISTS AND MICROGLIAL CELLS 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12428 18464925 14551 17034 9236 PPARG PPAR PPAR-G 3 2.2 In this view PPAR-_amp_#x003b3 agonists have been extensively studied in the last decade for 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12429 18464925 14552 17034 9236 PPARG PPAR PPAR-G 46 2.2 provided by Petrova et al 74 who demonstrated that this PPAR-_amp_#x003b3 natural ligand attenuates iNOS expression and the subsequent NO accumulation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12430 18464925 14552 14535 7873 NOS2A iNOS iNOS 51 2.2 al 74 who demonstrated that this PPAR-_amp_#x003b3 natural ligand attenuates iNOS expression and the subsequent NO accumulation in the murine BV-2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12431 18464925 14552 10676 6121 IRF6 LPS LPS 67 0.3 accumulation in the murine BV-2 microglial cell line stimulated by LPS 11 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 12432 18464925 14553 14535 7873 NOS2A iNOS iNOS 17 2.2 the NO pathway it was suggested that 15d-PGJ 2 inhibits iNOS expression by a PPAR-_amp_#x003b3 independent mechanism 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12433 18464925 14553 17034 9236 PPARG PPAR PPAR-G 21 2.2 was suggested that 15d-PGJ 2 inhibits iNOS expression by a PPAR-_amp_#x003b3 independent mechanism 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12434 18464925 14554 22551 11892 TNF TNF TNF-A 12 0.3 authors then demonstrated that 15d-PGJ 2 decreases the production of TNF-_amp_#x003b1 IL-1 _amp_#x003b2 and the expression of COX-2 in the same 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12435 18464925 14554 10437 5992 IL1B IL-1 IL-1 15 1.3 then demonstrated that 15d-PGJ 2 decreases the production of TNF-_amp_#x003b1 IL-1 _amp_#x003b2 and the expression of COX-2 in the same cell 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12436 18464925 14554 17610 9605 PTGS2 COX-2 COX-2 21 3.0 the production of TNF-_amp_#x003b1 IL-1 _amp_#x003b2 and the expression of COX-2 in the same cell system while increasing the expression of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12437 18464925 14555 17034 9236 PPARG PPAR PPAR-G 19 2.2 first time that primary microglial cells unlike BV-2 cells express PPAR-_amp_#x003b3 and that such basal expression is increased by its specific 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12438 18464925 14555 10676 6121 IRF6 LPS LPS 44 0.3 is reduced in the presence of microglial activators such as LPS and IFN-_amp_#x003b3 11 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 12439 18464925 14555 9905 5438 IFNG IFN IFN-G 46 0.3 in the presence of microglial activators such as LPS and IFN-_amp_#x003b3 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000680322007644829<>ScoreDetail__5438|IFNG|0.000509748271281208__5417|IFNA1|0.000680322007644829__ 0 0 0 0 0 12440 18464925 14556 17034 9236 PPARG PPAR PPAR-G 1 2.2 Microglial PPAR-_amp_#x003b3 was subsequently shown to be functionally active being able to 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12441 18464925 14557 10676 6121 IRF6 LPS LPS-induced 12 0.3 BV-2 cell line in primary microglial cultures 15d-PGJ 2 prevented LPS-induced iNOS expression and TNF-_amp_#x003b1 production as well as IFN-_amp_#x003b3 -induced 11 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 12442 18464925 14557 14535 7873 NOS2A iNOS iNOS 13 2.2 cell line in primary microglial cultures 15d-PGJ 2 prevented LPS-induced iNOS expression and TNF-_amp_#x003b1 production as well as IFN-_amp_#x003b3 -induced expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12443 18464925 14557 22551 11892 TNF TNF TNF-A 16 0.3 primary microglial cultures 15d-PGJ 2 prevented LPS-induced iNOS expression and TNF-_amp_#x003b1 production as well as IFN-_amp_#x003b3 -induced expression of major histocompatibility 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12444 18464925 14557 9905 5438 IFNG IFN IFN-G 22 0.3 prevented LPS-induced iNOS expression and TNF-_amp_#x003b1 production as well as IFN-_amp_#x003b3 -induced expression of major histocompatibility complex (MHC) MHC class II 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000680322007644829<>ScoreDetail__5438|IFNG|0.000509748271281208__5417|IFNA1|0.000680322007644829__ 0 0 0 0 0 12445 18464925 14557 9353 4931 HLA-A MHC MHC 30 1.8 well as IFN-_amp_#x003b3 -induced expression of major histocompatibility complex (MHC) MHC class II antigens by mechanisms involving PPAR-_amp_#x003b3 activation and reduced 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12446 18464925 14557 17034 9236 PPARG PPAR PPAR-G 37 2.2 histocompatibility complex (MHC) MHC class II antigens by mechanisms involving PPAR-_amp_#x003b3 activation and reduced activation of STAT-1 and NF-_amp_#x003ba B which 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12447 18464925 14557 21414 11362 STAT1 STAT1 STAT-1 44 1.2 antigens by mechanisms involving PPAR-_amp_#x003b3 activation and reduced activation of STAT-1 and NF-_amp_#x003ba B which are known to mediate IFN-_amp_#x003b3 and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12448 18464925 14557 9905 5438 IFNG IFN IFN-G 54 0.3 of STAT-1 and NF-_amp_#x003ba B which are known to mediate IFN-_amp_#x003b3 and LPS signaling 76 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000680322007644829<>ScoreDetail__5438|IFNG|0.000509748271281208__5417|IFNA1|0.000680322007644829__ 0 0 0 0 0 12449 18464925 14557 10676 6121 IRF6 LPS LPS 57 0.3 and NF-_amp_#x003ba B which are known to mediate IFN-_amp_#x003b3 and LPS signaling 76 11 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 12450 18464925 14558 21414 11362 STAT1 STAT1 STAT-1 17 1.2 did not affect NF-_amp_#x003ba B binding activity although it decreased STAT-1 expression and enhanced expression and binding activity of the AP-1 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12451 18464925 14558 7683 3796 FOS AP-1 AP-1 27 2.8 STAT-1 expression and enhanced expression and binding activity of the AP-1 proteins J-Jun and c-Fos 60 1 JUMiner_v2.2 1 0 0 2 6204 TotalCon:5<>3796|FOS|2353|Complete__3797|FOSB|2354|Complete__6204|JUN|3725|Complete__6205|JUNB|3726|Complete__6206|JUND|3727|Complete__<>AvaiableGeneRif=5<>BEST:6204|JUN|0.000683500682540148<>ScoreDetail__3796|FOS|0.000640117116644211__3797|FOSB|0.000582137835736414__6205|JUNB|0.000635742739992884__6204|JUN|0.000683500682540148__6206|JUND|0.000638624949252125__ 0 0 0 0 0 12452 18464925 14559 10676 6121 IRF6 LPS LPS 22 0.3 primary microglia and mouse cell line N9 activated either by LPS alone or in combination with IFN-_amp_#x003b3 or TNF-_amp_#x003b1 63 77 11 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 12453 18464925 14559 9905 5438 IFNG IFN IFN-G 28 0.3 N9 activated either by LPS alone or in combination with IFN-_amp_#x003b3 or TNF-_amp_#x003b1 63 77 15d-PGJ 2 attenuated microglial activation also 11 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000680322007644829<>ScoreDetail__5438|IFNG|0.000509748271281208__5417|IFNA1|0.000680322007644829__ 0 0 0 0 0 12454 18464925 14559 22551 11892 TNF TNF TNF-A 31 0.3 either by LPS alone or in combination with IFN-_amp_#x003b3 or TNF-_amp_#x003b1 63 77 15d-PGJ 2 attenuated microglial activation also when elicited 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12455 18464925 14559 3758 10618 CCL2 MCP-1 MCP-1 64 2.6 of proinflammatory cytokines and the chemokine monocyte chemoattractant protein-1 (MCP-1) MCP-1 73 78 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12456 18464925 14560 10676 6121 IRF6 LPS LPS-induced 12 0.3 cortical mixed neuron-glial cultures 15d-PGJ 2 ciglitazone and troglitazone prevented LPS-induced neuronal death suggesting a PPAR-_amp_#x003b3 mediated mechanism of neuroprotection 79 11 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 12457 18464925 14560 17034 9236 PPARG PPAR PPAR-G 17 2.2 2 ciglitazone and troglitazone prevented LPS-induced neuronal death suggesting a PPAR-_amp_#x003b3 mediated mechanism of neuroprotection 79 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12458 18464925 14561 926 620 APP amyloid amyloid 21 1.0 ibuprofen reduced the neurotoxicity of microglial cells exposed to _amp_#x003b2 -amyloid fibrils 80 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 12459 18464925 14562 17610 9605 PTGS2 COX-2 COX-2-specific 4 2.5 In this cell system COX-2-specific inhibitors failed to promote neuronal survival suggesting protective mechanisms independent 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12460 18464925 14562 17610 9605 PTGS2 COX-2 COX-2 16 3.0 failed to promote neuronal survival suggesting protective mechanisms independent of COX-2 metabolism 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12461 18464925 14563 17034 9236 PPARG PPAR PPAR-G 27 2.2 NXC 2216 were able to prevent microglial activation by activating PPAR-_amp_#x003b3 36 37 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12462 18464925 14564 17034 9236 PPARG PPAR PPAR-G 8 2.2 Interestingly NCX 2216 after an initial activation induced PPAR-_amp_#x003b3 nitration and inactivation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12463 18464925 14564 22227 5057 TLX2 NCX NCX 1 0.0 Interestingly NCX 2216 after an initial activation induced PPAR-_amp_#x003b3 nitration and inactivation 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12464 18464925 14565 22551 11892 TNF TNF TNF-A 9 0.3 These effects were paralleled by a transient reduction of TNF-_amp_#x003b1 and NO production and a protracted inhibition of IL-1 _amp_#x003b2 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12465 18464925 14565 10437 5992 IL1B IL-1 IL-1 19 1.3 of TNF-_amp_#x003b1 and NO production and a protracted inhibition of IL-1 _amp_#x003b2 and PGE 2 synthesis suggesting a dynamic regulation of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12466 18464925 14565 22227 5057 TLX2 NCX NCX 37 0.0 dynamic regulation of the functional state of activated microglia by NCX 2216 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12467 18464925 14566 17034 9236 PPARG PPAR PPAR-G 13 2.2 NCX 2216 could therefore lead after an initial activation of PPAR-_amp_#x003b3 to a protracted suppression of its control over microglial activation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12468 18464925 14566 22227 5057 TLX2 NCX NCX 3 0.0 Long treatment with NCX 2216 could therefore lead after an initial activation of PPAR-_amp_#x003b3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12469 18464925 14567 926 620 APP amyloid amyloid 39 1.0 2216 in an AD animal model the reduction of cerebral amyloid load accompanied by a sustained microglial activation 82 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 12470 18464925 14567 22227 5057 TLX2 NCX NCX 28 0.0 by 81 only in the case of protracted administration of NCX 2216 in an AD animal model the reduction of cerebral 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12471 18464925 14568 17034 9236 PPARG PPAR PPAR-G 3 2.2 The contribution of PPAR-_amp_#x003b3 -dependent or independent mechanisms to the inhibition of microglial activation 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12472 18464925 14569 17034 9236 PPARG PPAR PPAR-G 23 2.2 2 at concentrations several fold lower than those required for PPAR-_amp_#x003b3 activation effectively reduced the LPS-stimulated production of PGJ 2 by 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12473 18464925 14569 10676 6121 IRF6 LPS LPS-stimulated 29 0.3 lower than those required for PPAR-_amp_#x003b3 activation effectively reduced the LPS-stimulated production of PGJ 2 by directly preventing the enzymatic activity 11 JUMiner_v2.2 1 2 lipopolysaccharide 0 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 12474 18464925 14569 17610 9605 PTGS2 COX-2 COX-2 41 3.0 of PGJ 2 by directly preventing the enzymatic activity of COX-2 rather than its expression as previously described in activated monocytic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12475 18464925 14570 17610 9605 PTGS2 COX-2 COX-2 3 3.0 The reduction of COX-2 enzymatic activity could be achieved through the modifications of key 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12476 18464925 14571 17034 9236 PPARG PPAR PPAR-G 10 2.2 At concentration 10 times higher than those required to activate PPAR-_amp_#x003b3 15d-PGJ 2 induced microglial cell impairment and death by apoptosis 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12477 18464925 14573 17034 9236 PPARG PPAR PPAR-G 21 2.2 the link between the proapoptotic effect of 15d-PGJ 2 and PPAR-_amp_#x003b3 activation is still controversial 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12478 18464925 14575 17034 9236 PPARG PPAR PPAR-G 27 2.2 and human and rat glioma cell lines appears mediated by PPAR-_amp_#x003b3 -dependent mechanisms 61 87 89 _amp_#x02013 91 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12479 18464925 14578 17034 9236 PPARG PPAR PPAR-G 17 2.2 an increasing number of experimental studies supporting the use of PPAR-_amp_#x003b3 ligands to treat major disabling brain diseases with a high 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12480 18464925 14580 17034 9236 PPARG PPAR PPAR-G 13 2.2 in animal models of AD due to the ability of PPAR-_amp_#x003b3 agonists to reduced inflammation and the amyloid burden by various 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12481 18464925 14580 926 620 APP amyloid amyloid 21 1.0 the ability of PPAR-_amp_#x003b3 agonists to reduced inflammation and the amyloid burden by various mechanisms have found some validation in a 11 JUMiner_v2.2 1 1 UserEdit 0 0 0 1 1 888 598 APLP2 0 12482 18464925 14582 17034 9236 PPARG PPAR PPAR-G 9 2.2 Similarly the better neurological outcome reported after administration of PPAR-_amp_#x003b3 ligands in experimental stroke models are consistent with the result 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12483 18464925 14584 17034 9236 PPARG PPAR PPAR-G 4 2.2 The clinical use of PPAR-_amp_#x003b3 agonists in MS and ASL remains poorly investigated 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12484 18464925 14584 1184 746 ASL ASL ASL 10 0.0 The clinical use of PPAR-_amp_#x003b3 agonists in MS and ASL remains poorly investigated 1 JUMiner_v2.2 1 0 0 2 291 TotalCon:2<>746|ASL|435|Complete__291|ADSL|158|Complete__<>AvaiableGeneRif=2<>BEST:291|ADSL|0.000516212447956619<>ScoreDetail__291|ADSL|0.000516212447956619__746|ASL|0.000364373752415956__ 0 0 0 0 0 12485 18464925 14586 9947 5468 IGFALS ALS ALS 10 0.3 A first clinical trial for the use of pioglitazone in ALS started in Germany in late 2007 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.00050067446478045<>ScoreDetail__5468|IGFALS|0.000328025032588574__11179|SOD1|0.00050067446478045__ 0 0 0 0 0 12486 18464925 14587 17034 9236 PPARG PPAR PPAR-G 1 2.2 Although PPAR-_amp_#x003b3 synthetic ligands such as TZDs and NSAIDs appear to be 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12487 18464925 14588 17034 9236 PPARG PPAR PPAR-G 8 2.2 Among these the toxic effect associated with some PPAR-_amp_#x003b3 agonists and their blood-brain-barrier permeability which are at present still 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12488 18464925 14589 17034 9236 PPARG PPAR PPAR-G 9 2.2 A deep knowledge of the molecular mechanisms evoked by PPAR-_amp_#x003b3 ligands either dependent or independent of the receptor activation and 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 12489 18464925 14589 17034 9236 PPARG PPAR PPAR-G 38 2.2 the specific cell type is mandatory for the development of PPAR-_amp_#x003b3 drugs with increasing efficacy and safety 11 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2523 18513389 3474 20996 11179 SOD1 ALS ALS 13 2.5 predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS) ALS have been identified but the pathology itself seems to be 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2524 18513389 3476 20996 11179 SOD1 ALS ALS 37 2.5 coagulation inflammation cellular adhesion and matrix integrity in 54 sporadic ALS patients and 208 controls 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2525 18513389 3481 20996 11179 SOD1 ALS ALS 10 2.5 An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2526 18513389 3486 20996 11179 SOD1 ALS ALS 18 2.5 method offers a new insight into genetic markers of sporadic ALS pointing out the existence of a strong genetic background 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2527 18513389 3488 20996 11179 SOD1 ALS ALS 3 2.5 Amyotrophic lateral sclerosis (ALS), ALS the most common form of motoneuron disease is a relatively 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2528 18513389 3490 20996 11179 SOD1 SOD1 SOD1 8 3.2 gene coding for copper/zinc copper zinc superoxide dismutase 1 (SOD1) SOD1 appears to be mutated in 10_amp_#x02013 20% in the familial 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2529 18513389 3491 20996 11179 SOD1 ALS ALS 4 2.5 Genetic risk factors for ALS have been extensively studied and some major genes in addition 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2530 18513389 3491 20996 11179 SOD1 SOD1 SOD1 16 3.2 been extensively studied and some major genes in addition to SOD1 have been recognised as being responsible for the monogenic inheritance 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2531 18513389 3492 20996 11179 SOD1 ALS ALS 10 2.5 There are now at least six dominant inherited adult onset ALS genes of which only three have been identified so far 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2532 18513389 3493 20996 11179 SOD1 ALS ALS 2 2.5 However most ALS cases seem to be a typical multifactorial disease deriving from 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2533 18513389 3496 20996 11179 SOD1 ALS ALS 9 2.5 Among the genetic factors that may predispose to sporadic ALS neurofilaments apolipoprotein epsilon 4 genotype excitotoxicity genes ciliary neurotrophic factor 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2534 18513389 3496 5353 2615 CYP2B6 P450 P450 22 1.9 4 genotype excitotoxicity genes ciliary neurotrophic factor (CTNF), CTNF cytochrome P450 debrisoquine hydroxylase CYP2D6 apurinic apyrimidinic endonuclease (APEX), APEX mitochondrial manganese 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2535 18513389 3496 5359 2625 CYP2D6 CYP2D6 CYP2D6 25 1.2 genes ciliary neurotrophic factor (CTNF), CTNF cytochrome P450 debrisoquine hydroxylase CYP2D6 apurinic apyrimidinic endonuclease (APEX), APEX mitochondrial manganese superoxide dismutase SOD2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2536 18513389 3496 879 17889 APEX2 APEX APEX 29 0.3 CTNF cytochrome P450 debrisoquine hydroxylase CYP2D6 apurinic apyrimidinic endonuclease (APEX), APEX mitochondrial manganese superoxide dismutase SOD2 monoamine oxidase allele B and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2537 18513389 3496 20997 11180 SOD2 SOD2 SOD2 34 0.9 CYP2D6 apurinic apyrimidinic endonuclease (APEX), APEX mitochondrial manganese superoxide dismutase SOD2 monoamine oxidase allele B and paraoxonases have been reported in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2538 18513389 3499 20996 11179 SOD1 ALS ALS 27 2.5 have identified SNPs (single single nucleotide polymorphisms potentially associated with ALS 13 -16 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2539 18513389 3502 20996 11179 SOD1 ALS ALS 11 2.5 so far no microarrays panel has been specifically developed for ALS and the aetiology of the disease still remains to be 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2540 18513389 3509 20996 11179 SOD1 ALS ALS 36 2.5 disease prompted us to employ the same approach also in ALS hoping to discover specific genetic patterns underlying the sporadic form 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2541 18513389 3510 20996 11179 SOD1 ALS ALS 18 2.5 in genes that could be involved in the pathogenesis of ALS disease since it has been demonstrated that inflammation cellular adhesion 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2542 18513389 3511 20996 11179 SOD1 ALS ALS 24 2.5 homocysteine metabolism and matrix integrity pathways are directly linked to ALS even though they could be indirectly 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2543 18513389 3512 20996 11179 SOD1 ALS ALS 2 2.5 Genotyping of ALS cases and controls was performed 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2544 18513389 3516 20996 11179 SOD1 ALS ALS 19 2.5 origin belonging to Italian ancestry and consisted of 54 sporadic ALS (SALS) SALS patients and 208 control subjects 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2545 18513389 3517 20996 11179 SOD1 ALS ALS 3 2.5 Diagnostic Criteria for ALS disease were based on the World Federation of Neurology El 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2546 18513389 3518 20996 11179 SOD1 ALS ALS 10 2.5 All patients diagnosed to have Definite Probable or Probably laboratory-supported ALS who gave their informed consent were included in the study 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2547 18513389 3519 20996 11179 SOD1 ALS ALS 4 2.5 The diagnosis of Possible ALS was also accepted 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2548 18513389 3521 20996 11179 SOD1 SOD1 SOD1 38 3.2 of the family and when no mutations were present in SOD1 gene 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2549 18513389 3523 20996 11179 SOD1 ALS ALS 10 2.5 We checked the absence of personal and familial history of ALS in this group through direct interview 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2550 18513389 3527 11940 6667 LPA LPA LPA 6 0.3 The following polymorphisms (SNPs) SNPs were genotyped LPA 93C/T, 93C T 121 G/A, G A APOA4 thr347ser glu360his 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2551 18513389 3527 892 602 APOA4 APOA4 APOA4 10 0.3 were genotyped LPA 93C/T, 93C T 121 G/A, G A APOA4 thr347ser glu360his APOBthr71ile APOC3 641C/A, 641C A 482C/T, 482C T 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2552 18513389 3527 909 610 APOC3 APOC3 APOC3 14 0.3 93C T 121 G/A, G A APOA4 thr347ser glu360his APOBthr71ile APOC3 641C/A, 641C A 482C/T, 482C T 455 T/C, T C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2553 18513389 3527 912 613 APOE APOE APOE 25 1.3 C T 3175 C/G, C G 3206 T/G, T G APOE cys112arg arg158cys ADRB3 trp64arg PPAR_amp_#x003b3 pro12ala LIPC 480C/T, 480C T 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2554 18513389 3527 397 288 ADRB3 ADRB3 ADRB3 28 1.6 C/G, C G 3206 T/G, T G APOE cys112arg arg158cys ADRB3 trp64arg PPAR_amp_#x003b3 pro12ala LIPC 480C/T, 480C T LPL 93 T/G, 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2555 18513389 3527 11871 6619 LIPC LIPC LIPC 32 0.6 T/G, T G APOE cys112arg arg158cys ADRB3 trp64arg PPAR_amp_#x003b3 pro12ala LIPC 480C/T, 480C T LPL 93 T/G, T G asp9asn asn291ser 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2556 18513389 3527 11959 6677 LPL LPL LPL 34 1.6 cys112arg arg158cys ADRB3 trp64arg PPAR_amp_#x003b3 pro12ala LIPC 480C/T, 480C T LPL 93 T/G, T G asp9asn asn291ser ser447term PON1 met55leu gln192arg 1 JUMiner_v2.2 1 0 0 2 6677 TotalCon:2<>6677|LPL|4023|Complete__6528|LCP1|3936|Complete__<>AvaiableGeneRif=2<>BEST:6677|LPL|0.000470731518713269<>ScoreDetail__6528|LCP1|0.000353306953080837__6677|LPL|0.000470731518713269__ 0 0 0 0 0 2557 18513389 3527 16981 9204 PON1 PON1 PON1 40 1.8 480C T LPL 93 T/G, T G asp9asn asn291ser ser447term PON1 met55leu gln192arg PON2 ser311cys LDLR NcoI+/-, NcoI - CETP-631C/A, CETP-631C 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2558 18513389 3527 16982 9205 PON2 PON2 PON2 43 1.3 93 T/G, T G asp9asn asn291ser ser447term PON1 met55leu gln192arg PON2 ser311cys LDLR NcoI+/-, NcoI - CETP-631C/A, CETP-631C A -629 C/A, 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2559 18513389 3527 11736 6547 LDLR LDLR LDLR 45 1.8 T G asp9asn asn291ser ser447term PON1 met55leu gln192arg PON2 ser311cys LDLR NcoI+/-, NcoI - CETP-631C/A, CETP-631C A -629 C/A, C A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2560 18513389 3527 22551 11892 TNF TNF TNF 51 2.2 NcoI - CETP-631C/A, CETP-631C A -629 C/A, C A ile405val TNF beta thr26asn MTHFR 677 C/T, C T NOS3 -922 A/G, 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2561 18513389 3527 13818 7436 MTHFR MTHFR MTHFR 54 0.3 CETP-631C A -629 C/A, C A ile405val TNF beta thr26asn MTHFR 677 C/T, C T NOS3 -922 A/G, A G -690 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2562 18513389 3527 14538 7876 NOS3 NOS3 NOS3 57 1.2 A ile405val TNF beta thr26asn MTHFR 677 C/T, C T NOS3 -922 A/G, A G -690 C/T, C T glu298asp DCP1 1 JUMiner_v2.2 1 0 0 2 7876 TotalCon:2<>7876|NOS3|4846|Complete__22048|NANOS3|342977|Complete__<>AvaiableGeneRif=2<>BEST:7876|NOS3|0.000498603631227461<>ScoreDetail__22048|NANOS3|0.000361620057859209__7876|NOS3|0.000498603631227461__ 0 0 0 0 0 2563 18513389 3527 156 2707 ACE DCP1 DCP1 63 1.3 NOS3 -922 A/G, A G -690 C/T, C T glu298asp DCP1 IVS16 ins/del, ins del AGTR1 1166A/C, 1166A C AGT met235thr 1 JUMiner_v2.2 1 0 0 1 0 TotalCon:2<>2707|ACE|1636|Complete__24451|DCP1B|196513|No_GeneRif__<>AvaiableGeneRif=1<> 0 0 0 0 0 2564 18513389 3527 454 336 AGTR1 AGTR1 AGTR1 66 0.9 -690 C/T, C T glu298asp DCP1 IVS16 ins/del, ins del AGTR1 1166A/C, 1166A C AGT met235thr NPPA 664 G/A, G A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2565 18513389 3527 14612 7939 NPPA NPPA NPPA 70 0.9 IVS16 ins/del, ins del AGTR1 1166A/C, 1166A C AGT met235thr NPPA 664 G/A, G A NPPA 2238 T/C, T C ADD1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2566 18513389 3527 14612 7939 NPPA NPPA NPPA 73 0.9 1166A/C, 1166A C AGT met235thr NPPA 664 G/A, G A NPPA 2238 T/C, T C ADD1 gly460trp SCNN1A trp493arg ala663thr GNB3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2567 18513389 3527 19499 10599 SCNN1A SCNN1A SCNN1A 78 0.3 G/A, G A NPPA 2238 T/C, T C ADD1 gly460trp SCNN1A trp493arg ala663thr GNB3 825 C/T, C T ADRB2 arg16gly ADRB2 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2568 18513389 3527 8499 4400 GNB3 GNB3 GNB3 81 0.3 NPPA 2238 T/C, T C ADD1 gly460trp SCNN1A trp493arg ala663thr GNB3 825 C/T, C T ADRB2 arg16gly ADRB2 gln27glu MMP3 (-1171) 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2569 18513389 3527 396 286 ADRB2 ADRB2 ADRB2 84 1.6 ADD1 gly460trp SCNN1A trp493arg ala663thr GNB3 825 C/T, C T ADRB2 arg16gly ADRB2 gln27glu MMP3 (-1171) -1171 5A/6A, 5A 6A FII 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2570 18513389 3527 396 286 ADRB2 ADRB2 ADRB2 86 1.6 SCNN1A trp493arg ala663thr GNB3 825 C/T, C T ADRB2 arg16gly ADRB2 gln27glu MMP3 (-1171) -1171 5A/6A, 5A 6A FII 20210 G/A, 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2571 18513389 3527 13324 7173 MMP3 MMP3 MMP3 88 0.3 ala663thr GNB3 825 C/T, C T ADRB2 arg16gly ADRB2 gln27glu MMP3 (-1171) -1171 5A/6A, 5A 6A FII 20210 G/A, G A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2572 18513389 3527 7514 3662 FGB FGB FGB 107 0.3 arg353glu PAI -675 G5/G4, G5 G4 11053 G/T, G T FGB -455 G/A, G A ITGA2 873 G/A, G A ITGB3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2573 18513389 3527 19619 10718 SELE SELE SELE 115 0.6 G/A, G A ITGA2 873 G/A, G A ITGB3 leu33pro SELE ser128arg leu554phe ICAM gly214arg TNF alpha -376 G/A, G A 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2574 18513389 3527 22551 11892 TNF TNF TNF 120 2.2 G/A, G A ITGB3 leu33pro SELE ser128arg leu554phe ICAM gly214arg TNF alpha -376 G/A, G A -308G/A, -308G A -244 G/A, 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2575 18513389 3527 452 333 AGT AGT AGT 68 0.2 glu298asp DCP1 IVS16 ins/del, ins del AGTR1 1166A/C, 1166A C AGT met235thr NPPA 664 G/A, G A NPPA 2238 T/C, T 6 JUMiner_v2.2 1 0 0 2 333 TotalCon:2<>333|AGT|183|Complete__341|AGXT|189|Complete__<>AvaiableGeneRif=2<>BEST:333|AGT|0.000458954089552175<>ScoreDetail__333|AGT|0.000458954089552175__341|AGXT|0.000442817154184078__ 0 0 0 0 0 2576 18513389 3527 351 243 ADD1 ADD1 ADD1 76 0.1 NPPA 664 G/A, G A NPPA 2238 T/C, T C ADD1 gly460trp SCNN1A trp493arg ala663thr GNB3 825 C/T, C T ADRB2 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2577 18513389 3527 19725 8583 SERPINE1 PAI PAI 102 0.0 FV arg506gln FVII -230 10 bp del/ins, del ins arg353glu PAI -675 G5/G4, G5 G4 11053 G/T, G T FGB -455 1 JUMiner_v2.2 1 0 0 2 8583 TotalCon:2<>8583|SERPINE1|5054|Complete__8584|SERPINB2|5055|Complete__<>AvaiableGeneRif=2<>BEST:8583|SERPINE1|0.000382406265260087<>ScoreDetail__8584|SERPINB2|0.000351017000607165__8583|SERPINE1|0.000382406265260087__ 0 0 0 0 0 2578 18513389 3527 10717 6137 ITGA2 ITGA2 ITGA2 110 0.0 G4 11053 G/T, G T FGB -455 G/A, G A ITGA2 873 G/A, G A ITGB3 leu33pro SELE ser128arg leu554phe ICAM 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2579 18513389 3527 10740 6156 ITGB3 ITGB3 ITGB3 113 0.1 FGB -455 G/A, G A ITGA2 873 G/A, G A ITGB3 leu33pro SELE ser128arg leu554phe ICAM gly214arg TNF alpha -376 G/A, 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2580 18513389 3528 22551 11892 TNF TNF TNF 2 2.2 The marker TNF beta thr26asn is twice present in the arrays as a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2581 18513389 3529 20996 11179 SOD1 ALS ALS 1 2.5 All ALS subjects were screened for SOD1 mutation through PCR amplification and 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2582 18513389 3529 20996 11179 SOD1 SOD1 SOD1 6 3.2 All ALS subjects were screened for SOD1 mutation through PCR amplification and direct sequencing according to standard 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2583 18513389 3531 894 603 APOB APOB APOB 14 0.6 those markers for which only one genotype was present (APOB APOB Arg3500Gln CBS Ile278Thr CETP Asp442Gly 14G(+1) 14G 1 A and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2584 18513389 3531 4240 1869 CETP CETP CETP 18 1.8 only one genotype was present (APOB APOB Arg3500Gln CBS Ile278Thr CETP Asp442Gly 14G(+1) 14G 1 A and 14(+3) 14 3 T 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2585 18513389 3531 3570 1550 CBS CBS CBS 16 0.2 for which only one genotype was present (APOB APOB Arg3500Gln CBS Ile278Thr CETP Asp442Gly 14G(+1) 14G 1 A and 14(+3) 14 6 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2586 18513389 3533 20996 11179 SOD1 ALS ALS 6 2.5 The association of these variables with ALS status was tested by ANNs and the results were compared 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2587 18513389 3568 23261 10539 TSPAN31 SAS SAS 6 0.0 For the analysis of LDA the SAS version 6.04 (SAS SAS Institute Cary NC USA using forward 1 JUMiner_v2.2 1 0 0 2 19237 TotalCon:2<>10539|TSPAN31|6302|Complete__19237|NANS|54187|Complete__<>AvaiableGeneRif=2<>BEST:19237|NANS|0.000559255464480874<>ScoreDetail__10539|TSPAN31|0.000204918032786885__19237|NANS|0.000559255464480874__ 0 0 0 0 0 2588 18513389 3568 23261 10539 TSPAN31 SAS SAS 9 0.0 For the analysis of LDA the SAS version 6.04 (SAS SAS Institute Cary NC USA using forward stepwise procedure was employed 1 JUMiner_v2.2 1 0 0 2 19237 TotalCon:2<>10539|TSPAN31|6302|Complete__19237|NANS|54187|Complete__<>AvaiableGeneRif=2<>BEST:19237|NANS|0.000559255464480874<>ScoreDetail__10539|TSPAN31|0.000204918032786885__19237|NANS|0.000559255464480874__ 0 0 0 0 0 2589 18513389 3574 23447 12428 TWIST1 TWIST TWIST 2 1.0 -Optimized criterion TWIST system The TWIST system is an ensemble of two algorithms 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2590 18513389 3574 23447 12428 TWIST1 TWIST TWIST 5 1.0 -Optimized criterion TWIST system The TWIST system is an ensemble of two algorithms Training and Testing 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2591 18513389 3617 12382 7142 MARCKSL1 MLP MLPs 4 0.0 Two independent Multilayers Perceptrons (MLPs) MLPs with 4 hidden units are trained for 100 epochs and 13 JUMiner_v2.2 1 0 0 2 7512 TotalCon:3<>7142|MARCKSL1|65108|Complete__2472|CSRP3|8048|Complete__7512|MUC2|4583|Complete__<>AvaiableGeneRif=3<>BEST:7512|MUC2|0.000283227263687246<>ScoreDetail__2472|CSRP3|0.000157103825136612__7512|MUC2|0.000283227263687246__7142|MARCKSL1|9.31445603576751e-05__ 0 0 0 0 0 2592 18513389 3618 12382 7142 MARCKSL1 MLP MLPs 10 0.0 A function of the testing results of the two independent MLPs defines the fitness of each individual 13 JUMiner_v2.2 1 0 0 2 7512 TotalCon:3<>7142|MARCKSL1|65108|Complete__2472|CSRP3|8048|Complete__7512|MUC2|4583|Complete__<>AvaiableGeneRif=3<>BEST:7512|MUC2|0.000283227263687246<>ScoreDetail__2472|CSRP3|0.000157103825136612__7512|MUC2|0.000283227263687246__7142|MARCKSL1|9.31445603576751e-05__ 0 0 0 0 0 2593 18513389 3624 4850 2300 CPB2 CPU CPU 13 0.0 algorithms in C language and we used a Pentium III CPU to run the system on real data 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2594 18513389 3635 20996 11179 SOD1 SOD1 SOD1 6 3.2 All patients were previously screened for SOD1 gene mutation by sequence analysis and no genetic variations were 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2595 18513389 3638 22551 11892 TNF TNF TNF 15 2.2 procedure (multiplex multiplex and hybridization steps was checked by the TNF beta thr26asn polymorphism that gave the same results in both 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2596 18513389 3645 23447 12428 TWIST1 TWIST TWIST 2 1.0 With the TWIST approach every experiment was conducted in a blind and independent 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2597 18513389 3645 23447 12428 TWIST1 TWIST TWIST 46 1.0 sub-sample A The results from the best five applications of TWIST procedures are reported in Table 4 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2598 18513389 3647 23447 12428 TWIST1 TWIST TWIST 3 1.0 In all the TWIST system experiments the 90% overall accuracy threshold was exceeded whereas 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2599 18513389 3649 23447 12428 TWIST1 TWIST TWIST 6 1.0 Genetic variants selected by the five TWIST procedures Seven genetic variants were always independently selected by the 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2600 18513389 3649 23447 12428 TWIST1 TWIST TWIST 18 1.0 Seven genetic variants were always independently selected by the five TWIST procedures apolipoprotein E (APOE) APOE (chromosome chromosome 19q13.2 arg158cys hepatic 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2601 18513389 3649 912 613 APOE APOE APOE 22 1.3 independently selected by the five TWIST procedures apolipoprotein E (APOE) APOE (chromosome chromosome 19q13.2 arg158cys hepatic lipase (LIPC) LIPC (chromosome chromosome 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2602 18513389 3649 11871 6619 LIPC LIPC LIPC 28 0.6 E (APOE) APOE (chromosome chromosome 19q13.2 arg158cys hepatic lipase (LIPC) LIPC (chromosome chromosome 15q21-23 -480 C/T; C T endothelial nitric oxide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2603 18513389 3649 14538 7876 NOS3 NOS3 NOS3 37 1.2 15q21-23 -480 C/T; C T endothelial nitric oxide synthase (NOS3) NOS3 (chromosome chromosome 7q36 690 C/T C T and glu298asp vitamin 1 JUMiner_v2.2 1 0 0 2 7876 TotalCon:2<>7876|NOS3|4846|Complete__22048|NANOS3|342977|Complete__<>AvaiableGeneRif=2<>BEST:7876|NOS3|0.000498603631227461<>ScoreDetail__22048|NANOS3|0.000361620057859209__7876|NOS3|0.000498603631227461__ 0 0 0 0 0 2604 18513389 3649 19619 10718 SELE SELE SELE 61 0.6 ITGA2 (chromosome chromosome 5q23-q31 873 G/A; G A E-selectin (SELE) SELE (chromosome chromosome 1q22-q25 ser128arg 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2605 18513389 3649 10717 6137 ITGA2 ITGA2 ITGA2 55 0.0 F7 (chromosome chromosome 13q34 arg353glu glycoprotein Ia/IIa Ia IIa (ITGA2) ITGA2 (chromosome chromosome 5q23-q31 873 G/A; G A E-selectin (SELE) SELE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2606 18513389 3652 23447 12428 TWIST1 TWIST TWIST 6 1.0 Genetic variants independently selected by four TWIST procedures The number of genetic variants selected four times over 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2607 18513389 3652 17034 9236 PPARG PPARG PPARG 26 2.2 five experiments consisted of peroxisome proliferator activated receptor gamma (PPARG) PPARG pro12ala (chromosome chromosome 3p25 lipoprotein lipase (LPL) LPL asp9asn (chromosome 1 JUMiner_v2.2 1 0 0 2 9236 TotalCon:2<>9236|PPARG|5468|Complete__16039|ANGPTL4|51129|Complete__<>AvaiableGeneRif=2<>BEST:9236|PPARG|0.000411682066219352<>ScoreDetail__9236|PPARG|0.000411682066219352__16039|ANGPTL4|0.000340421190831027__ 0 0 0 0 0 2608 18513389 3652 11959 6677 LPL LPL LPL 32 1.6 gamma (PPARG) PPARG pro12ala (chromosome chromosome 3p25 lipoprotein lipase (LPL) LPL asp9asn (chromosome chromosome 8p22 paraoxonase 1 (PON1) PON1 met55leu and 1 JUMiner_v2.2 1 0 0 2 6677 TotalCon:2<>6677|LPL|4023|Complete__6528|LCP1|3936|Complete__<>AvaiableGeneRif=2<>BEST:6677|LPL|0.000470731518713269<>ScoreDetail__6528|LCP1|0.000353306953080837__6677|LPL|0.000470731518713269__ 0 0 0 0 0 2609 18513389 3652 16981 9204 PON1 PON1 PON1 38 1.8 lipase (LPL) LPL asp9asn (chromosome chromosome 8p22 paraoxonase 1 (PON1) PON1 met55leu and paraoxonase 2 (PON2) PON2 ser311cys (chromosome chromosome 7q21.3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2610 18513389 3652 16982 9205 PON2 PON2 PON2 43 1.3 8p22 paraoxonase 1 (PON1) PON1 met55leu and paraoxonase 2 (PON2) PON2 ser311cys (chromosome chromosome 7q21.3 tumor necrosis factor beta (TNF TNF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2611 18513389 3652 22551 11892 TNF TNF TNF 51 2.2 PON2 ser311cys (chromosome chromosome 7q21.3 tumor necrosis factor beta (TNF TNF beta thr26 asn (chrom chrom 6p21.3 methylenetetrahydrofolate reductase (MTHFR) MTHFR 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2612 18513389 3652 13818 7436 MTHFR MTHFR MTHFR 59 0.3 TNF beta thr26 asn (chrom chrom 6p21.3 methylenetetrahydrofolate reductase (MTHFR) MTHFR 677 C/T C T (chrom chrom 1p36.3 angiotensin II receptor 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2613 18513389 3652 454 336 AGTR1 AGTR1 AGTR1 68 0.9 C T (chrom chrom 1p36.3 angiotensin II receptor type1 (AGTR1) AGTR1 1166 A/C A C (chromosome chromosome 3q21-25 atrial natriuretic peptide 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2614 18513389 3652 14612 7939 NPPA NPPA NPPA 76 0.9 A/C A C (chromosome chromosome 3q21-25 atrial natriuretic peptide (NPPA) NPPA 664 G/A G A (chrom chrom 1p36-21 epithelial Na channel 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2615 18513389 3652 19499 10599 SCNN1A SCNN1A SCNN1A 85 0.3 G A (chrom chrom 1p36-21 epithelial Na channel subunit (SCNN1A) SCNN1A trp493arg (chromosome chromosome 12p13 FVII -232 ins/del, ins del SELE 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2616 18513389 3652 19619 10718 SELE SELE SELE 92 0.6 SCNN1A trp493arg (chromosome chromosome 12p13 FVII -232 ins/del, ins del SELE leu554phe Tumor Necrosis Factor alpha (TNFalpha) TNFalpha -376 G/A G 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2617 18513389 3652 22551 11892 TNF TNFalpha TNFalpha 98 2.2 ins/del, ins del SELE leu554phe Tumor Necrosis Factor alpha (TNFalpha) TNFalpha -376 G/A G A and -308 G/A G A (chromosome 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2618 18513389 3653 22551 11892 TNF TNF TNF 1 2.2 The TNF beta thr26asn was used as further control 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2619 18513389 3654 23447 12428 TWIST1 TWIST TWIST 6 1.0 First it was selected by four TWIST systems and later since the information linked to such a 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2620 18513389 3654 23447 12428 TWIST1 TWIST TWIST 24 1.0 to such a variation was already recruited none of the TWIST systems selected this SNP 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2621 18513389 3655 23447 12428 TWIST1 TWIST TWIST 6 1.0 Genetic variants never selected by any TWIST procedures The following gene/genetic gene genetic variants were never selected 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2622 18513389 3655 23447 12428 TWIST1 TWIST TWIST 18 1.0 gene/genetic gene genetic variants were never selected by the five TWIST procedures apolipoprotein A4 (APOA4) APOA4 (chromosome chromosome 11q23 thr347ser apolipoprotein 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2623 18513389 3655 892 602 APOA4 APOA4 APOA4 22 0.3 never selected by the five TWIST procedures apolipoprotein A4 (APOA4) APOA4 (chromosome chromosome 11q23 thr347ser apolipoprotein C3 (APOC3) APOC3 (chromosome chromosome 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2624 18513389 3655 909 610 APOC3 APOC3 APOC3 28 0.3 A4 (APOA4) APOA4 (chromosome chromosome 11q23 thr347ser apolipoprotein C3 (APOC3) APOC3 (chromosome chromosome 11q23.1-q23.2 -641 C/A C A and 482 C/T; 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2625 18513389 3655 397 288 ADRB3 ADRB3 ADRB3 40 1.6 and 482 C/T; C T beta 3 adrenergic receptor (ADRB3) ADRB3 trp64arg (8p12-p11.2); 8p12-p11.2 LPL ser447term PON1 gln192arg low density lipoprotein 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2626 18513389 3655 11959 6677 LPL LPL LPL 43 1.6 T beta 3 adrenergic receptor (ADRB3) ADRB3 trp64arg (8p12-p11.2); 8p12-p11.2 LPL ser447term PON1 gln192arg low density lipoprotein receptor (LDLR) LDLR (chromosome 1 JUMiner_v2.2 1 0 0 2 6677 TotalCon:2<>6677|LPL|4023|Complete__6528|LCP1|3936|Complete__<>AvaiableGeneRif=2<>BEST:6677|LPL|0.000470731518713269<>ScoreDetail__6528|LCP1|0.000353306953080837__6677|LPL|0.000470731518713269__ 0 0 0 0 0 2627 18513389 3655 16981 9204 PON1 PON1 PON1 45 1.8 3 adrenergic receptor (ADRB3) ADRB3 trp64arg (8p12-p11.2); 8p12-p11.2 LPL ser447term PON1 gln192arg low density lipoprotein receptor (LDLR) LDLR (chromosome chromosome 19p13.3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2628 18513389 3655 11736 6547 LDLR LDLR LDLR 51 1.8 8p12-p11.2 LPL ser447term PON1 gln192arg low density lipoprotein receptor (LDLR) LDLR (chromosome chromosome 19p13.3 exon 18 NcoI +/-; - cholesteryl ester 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2629 18513389 3655 4240 1869 CETP CETP CETP 62 1.8 exon 18 NcoI +/-; - cholesteryl ester transfer protein (CETP) CETP -631 C/A C A and -629 C/A C A (chromosome 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2630 18513389 3655 14538 7876 NOS3 NOS3 NOS3 70 1.2 C A and -629 C/A C A (chromosome chromosome 16q21 NOS3 922 A/G; A G G-protein beta 3 subunit (GNB3) GNB3 1 JUMiner_v2.2 1 0 0 2 7876 TotalCon:2<>7876|NOS3|4846|Complete__22048|NANOS3|342977|Complete__<>AvaiableGeneRif=2<>BEST:7876|NOS3|0.000498603631227461<>ScoreDetail__22048|NANOS3|0.000361620057859209__7876|NOS3|0.000498603631227461__ 0 0 0 0 0 2631 18513389 3655 8499 4400 GNB3 GNB3 GNB3 77 0.3 NOS3 922 A/G; A G G-protein beta 3 subunit (GNB3) GNB3 825 C/T C T (chromosome chromosome 12p13 beta 2 adrenergic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2632 18513389 3655 7514 3662 FGB FGB FGB 92 0.3 receptor (ADBR2) ADBR2 arg16gly (chromosome chromosome 5q31-q32 beta fibrinogen (FGB) FGB -455 G/A G A (chromosome chromosome 4q28 TNF alfa -238 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2633 18513389 3655 22551 11892 TNF TNF TNF 97 2.2 fibrinogen (FGB) FGB -455 G/A G A (chromosome chromosome 4q28 TNF alfa -238 G/A G A and TNF beta thr26asn 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2634 18513389 3655 22551 11892 TNF TNF TNF 102 2.2 (chromosome chromosome 4q28 TNF alfa -238 G/A G A and TNF beta thr26asn 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2635 18513389 3657 20996 11179 SOD1 ALS ALS 5 2.5 The mechanism of neurodegeneration in ALS remains an enigma 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2636 18513389 3661 20996 11179 SOD1 ALS ALS 24 2.5 these new analytical tools shows that even in so-called sporadic ALS the genetic background plays a fundamental role 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2637 18513389 3662 20996 11179 SOD1 ALS ALS 13 2.5 in approaching the molecular basis of a rare disease like ALS in a conventional manner is related to the difficulty of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2638 18513389 3669 20996 11179 SOD1 ALS ALS 18 2.5 allelic variants that are likely to produce accurate predictions of ALS for a single individual regardless of some possible limitations such 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2639 18513389 3670 20996 11179 SOD1 ALS ALS 13 2.5 more than 50 medical cases with an accurate diagnosis of ALS and we were able to test them for 69 SNPs 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2640 18513389 3672 20996 11179 SOD1 ALS ALS 2 2.5 Besides all ALS patients were previously screened for SOD1 gene mutations with negative 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2641 18513389 3672 20996 11179 SOD1 SOD1 SOD1 8 3.2 Besides all ALS patients were previously screened for SOD1 gene mutations with negative results thus confirming the sporadic nature 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2642 18513389 3675 22551 11892 TNF TNF TNF 18 2.2 previously validated by ourselves 17 and others 26 and contains TNF beta as the internal control 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2643 18513389 3676 912 613 APOE APOE ApoE 1 1.3 Indeed ApoE arg158cys was selected by all the five TWISTs while the 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2644 18513389 3676 23447 12428 TWIST1 TWIST TWISTs 9 1.0 Indeed ApoE arg158cys was selected by all the five TWISTs while the ApoE cys112arg was selected only once 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2645 18513389 3676 912 613 APOE APOE ApoE 12 1.3 arg158cys was selected by all the five TWISTs while the ApoE cys112arg was selected only once 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2646 18513389 3677 14533 7872 NOS1 NOS NOS 1 1.2 For NOS variants the position -922 in the promoter region was never 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000455125273343148<>ScoreDetail__7873|NOS2A|0.000418757020633272__7872|NOS1|0.000455125273343148__ 0 0 0 0 0 2647 18513389 3677 23447 12428 TWIST1 TWIST TWISTs 37 1.0 in position 698 were both selected by all the five TWISTs 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2648 18513389 3678 19619 10718 SELE SELE SELE 6 0.6 The two Factor VII and Selectin (SELE) SELE genetic variants both containing the information necessary for the correct 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2649 18513389 3678 19619 10718 SELE SELE SELE 31 0.6 healthy status were selected five times (FVII FVII arg353glu and SELE ser128arg and four times (FVII FVII del/ins del ins and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2650 18513389 3678 19619 10718 SELE SELE SELE 39 0.6 ser128arg and four times (FVII FVII del/ins del ins and SELE leu554phe respectively 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2651 18513389 3679 20996 11179 SOD1 ALS ALS 8 2.5 The role of the paroxonase in predisposing to ALS disease appears to be confirmed PON1 met 55leu and PON2 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2652 18513389 3679 16981 9204 PON1 PON1 PON1 14 1.8 paroxonase in predisposing to ALS disease appears to be confirmed PON1 met 55leu and PON2 ser311cys were chosen four times whereas 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2653 18513389 3679 16982 9205 PON2 PON2 PON2 18 1.3 ALS disease appears to be confirmed PON1 met 55leu and PON2 ser311cys were chosen four times whereas PON1 gln192arg was never 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2654 18513389 3679 16981 9204 PON1 PON1 PON1 25 1.8 met 55leu and PON2 ser311cys were chosen four times whereas PON1 gln192arg was never 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2655 18513389 3680 20996 11179 SOD1 ALS ALS 16 2.5 we can assume a generic role of this receptor on ALS disease since PPAR_amp_#x003b3 is at the crossroads between lipid metabolism 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2656 18513389 3681 22551 11892 TNF TNF TNF 10 2.2 In addition we noticed for example that in the same TNF locus 6p21.3 lies also the HFE gene for hemocromatosis and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2657 18513389 3681 9203 4886 HFE HFE HFE 16 0.5 that in the same TNF locus 6p21.3 lies also the HFE gene for hemocromatosis and the peripherin gene both previously involved 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2658 18513389 3681 20996 11179 SOD1 ALS ALS 28 2.5 for hemocromatosis and the peripherin gene both previously involved in ALS disease 35 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2659 18513389 3682 23447 12428 TWIST1 TWIST TWIST 10 1.0 Few genetic variants were never selected by any of the TWIST procedures 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2660 18513389 3683 16981 9204 PON1 PON1 PON1 17 1.8 had already been picked up by the systems e.g for PON1 NOS and TNF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2661 18513389 3683 14533 7872 NOS1 NOS NOS 18 1.2 already been picked up by the systems e.g for PON1 NOS and TNF 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000455125273343148<>ScoreDetail__7873|NOS2A|0.000418757020633272__7872|NOS1|0.000455125273343148__ 0 0 0 0 0 2662 18513389 3683 22551 11892 TNF TNF TNF 20 2.2 picked up by the systems e.g for PON1 NOS and TNF 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2663 18513389 3684 892 602 APOA4 APOA4 APOA4 2 0.3 Moreover regarding APOA4 and APO C3 variants we observed that they lie on 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2664 18513389 3684 2459 1361 C9orf3 APO APO 4 0.3 Moreover regarding APOA4 and APO C3 variants we observed that they lie on chromosome 11 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2665 18513389 3685 20996 11179 SOD1 ALS ALS 10 2.5 Indeed a very recent paper on genome wide genotyping in ALS 13 found no SNPs associated with the disease on chromosome 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2666 18513389 3686 912 613 APOE APOE ApoE 17 1.3 gene variations confirm some of the already known results (ApoE ApoE and PON for example and identify new gene/genetic gene genetic 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2667 18513389 3686 16981 9204 PON1 PON PON 19 1.8 confirm some of the already known results (ApoE ApoE and PON for example and identify new gene/genetic gene genetic variations not 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2668 18513389 3687 14533 7872 NOS1 NOS NOS 12 1.2 the involvement of oxidative stress as well as angiogenesis (NOS) NOS and immune response (TNF) TNF pathways 1 JUMiner_v2.2 1 0 0 2 7872 TotalCon:2<>7872|NOS1|4842|Complete__7873|NOS2A|4843|Complete__<>AvaiableGeneRif=2<>BEST:7872|NOS1|0.000455125273343148<>ScoreDetail__7873|NOS2A|0.000418757020633272__7872|NOS1|0.000455125273343148__ 0 0 0 0 0 2669 18513389 3687 22551 11892 TNF TNF TNF 16 2.2 as well as angiogenesis (NOS) NOS and immune response (TNF) TNF pathways 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2670 18513389 3688 11871 6619 LIPC LIPC LIPC 11 0.6 results shed light on the involvement of lipid pathways (LIPC, LIPC PPAR_amp_#x003b3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2671 18513389 3689 20996 11179 SOD1 ALS ALS 21 2.5 the misfolding protein aggregations in several neurodegenerative diseases including familial ALS 36 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2672 18513389 3693 20996 11179 SOD1 ALS ALS 10 2.5 We analysed genetic variables within genes possibly involved in the ALS disease and thanks to artificial intelligence agents such as those 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2673 18513389 3693 20996 11179 SOD1 ALS ALS 42 2.5 genetic data only we were are able to conveniently differentiate ALS cases from control subjects 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2674 18513389 3695 20996 11179 SOD1 ALS ALS 33 2.5 this study offers new insight into genetic markers of sporadic ALS pointing out the existence of a strong genetic background 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2675 18513389 3696 20996 11179 SOD1 ALS ALS 17 2.5 future research on the complexity of the genetic profile of ALS subjects 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000764651968728075<>ScoreDetail__5468|IGFALS|0.00070002310755889__11179|SOD1|0.000764651968728075__ 0 0 0 0 0 2676 18513389 3706 23447 12428 TWIST1 TWIST TWIST 8 1.0 Table 4 Results of ten experiment obtained applying TWIST procedure in an independent manner to the whole dataset 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 2677 18513389 3707 23447 12428 TWIST1 TWIST TWIST 14 1.0 with ANNs using only the seven genetic variants selected by TWIST procedure 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5021 18539342 5527 13668 7315 MS4A1 CD20 CD20 11 1.0 (MS) MS brains CPs show (immunohistochemistry immunohistochemistry to HLA-DR CD3 CD20 CD68 VCAM-1 CD138 T lymphocytes in vessels and stroma VCAM-1 1 JUMiner_v2.2 1 0 0 2 7315 TotalCon:2<>7315|MS4A1|931|Complete__20412|KRT20|54474|Complete__<>AvaiableGeneRif=2<>BEST:7315|MS4A1|0.00186799501867995<>ScoreDetail__7315|MS4A1|0.00186799501867995__20412|KRT20|0.00109955559627984__ 0 0 0 0 0 5022 18539342 5527 3901 1693 CD68 CD68 CD68 12 0.6 MS brains CPs show (immunohistochemistry immunohistochemistry to HLA-DR CD3 CD20 CD68 VCAM-1 CD138 T lymphocytes in vessels and stroma VCAM-1 expression 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5023 18539342 5527 23886 12663 VCAM1 VCAM-1 VCAM-1 13 0.9 brains CPs show (immunohistochemistry immunohistochemistry to HLA-DR CD3 CD20 CD68 VCAM-1 CD138 T lymphocytes in vessels and stroma VCAM-1 expression on 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5024 18539342 5527 19541 10658 SDC1 CD138 CD138 14 1.0 CPs show (immunohistochemistry immunohistochemistry to HLA-DR CD3 CD20 CD68 VCAM-1 CD138 T lymphocytes in vessels and stroma VCAM-1 expression on endothelia 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5025 18539342 5527 23886 12663 VCAM1 VCAM-1 VCAM-1 21 0.9 CD20 CD68 VCAM-1 CD138 T lymphocytes in vessels and stroma VCAM-1 expression on endothelia intense HLA-DR immunostaining on cells in CP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5026 18539342 5531 11629 6493 LAMC2 CSF CSF 12 0.3 CPs could represent a site for lymphocyte entry in the CSF and for CSF antigens presentation 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5027 18539342 5531 11629 6493 LAMC2 CSF CSF 15 0.3 a site for lymphocyte entry in the CSF and for CSF antigens presentation 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5028 18539342 5534 11629 6493 LAMC2 CSF CSF 23 0.3 parenchyma such as the leptomeninges and the cerebrospinal fluid (CSF), CSF in the pathogenetic process of multiple sclerosis (MS) MS and 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5029 18539342 5535 11629 6493 LAMC2 CSF CSF 33 0.3 CNS and as a link for antigen trafficking between the CSF and the peripheral blood ( Nathanson and Chun 1989 Kivis_amp_#xe4 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5030 18539342 5539 11629 6493 LAMC2 CSF CSF 8 0.3 The CP is in close contact with the CSF the CP epithelial cells (constituting constituting the blood_amp_#x2013 CSF barrier 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5031 18539342 5539 11629 6493 LAMC2 CSF CSF 15 0.3 the CSF the CP epithelial cells (constituting constituting the blood_amp_#x2013 CSF barrier form an interface between CSF and periphery since their 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5032 18539342 5539 11629 6493 LAMC2 CSF CSF 21 0.3 (constituting constituting the blood_amp_#x2013 CSF barrier form an interface between CSF and periphery since their apical side faces the CSF and 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5033 18539342 5539 11629 6493 LAMC2 CSF CSF 30 0.3 between CSF and periphery since their apical side faces the CSF and their basal side facing fenestrated capillaries has access to 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5034 18539342 5540 11629 6493 LAMC2 CSF CSF 17 0.3 of the main routes of entry of lymphocytes in the CSF for routine immune surveillance in the normal brain ( Kivis_amp_#xe4 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5035 18539342 5541 11629 6493 LAMC2 CSF CSF 18 0.3 of the CP could be to scavenge antigens from the CSF acting as an immunological link between CSF and blood ( 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5036 18539342 5541 11629 6493 LAMC2 CSF CSF 25 0.3 antigens from the CSF acting as an immunological link between CSF and blood ( Nathanson and Chun 1989 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5037 18539342 5546 20996 11179 SOD1 ALS ALS 65 0.0 6 brains from patients affected by amyotrophic lateral sclerosis (ALS), ALS a non-inflammatory neurological disease 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5038 18539342 5548 20996 11179 SOD1 ALS ALS 22 0.0 in control cases 59.4_amp_#xa0 years (range range 52_amp_#x2013 68 in ALS cases 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5039 18539342 5556 12436 6925 MBP MBP MBP 34 1.9 demyelinating lesions in previous studies using myelin basic protein (MBP) MBP immunostaining ( Vercellino et al. 2005 and Vercellino et al. 1 JUMiner_v2.2 1 0 0 2 6925 TotalCon:3<>6925|MBP|4155|Complete__9362|PRG2|5553|Complete__6922|MBL2|4153|Complete__<>AvaiableGeneRif=3<>BEST:6925|MBP|0.000694756734087544<>ScoreDetail__6925|MBP|0.000694756734087544__9362|PRG2|0.000241396385243872__6922|MBL2|0.000378460624408039__ 0 0 0 0 0 5040 18539342 5558 12436 6925 MBP MBP MBP 27 1.9 section where the CP tissue blocks had been obtained using MBP immunostaining 1 JUMiner_v2.2 1 0 0 2 6925 TotalCon:3<>6925|MBP|4155|Complete__9362|PRG2|5553|Complete__6922|MBL2|4153|Complete__<>AvaiableGeneRif=3<>BEST:6925|MBP|0.000694756734087544<>ScoreDetail__6925|MBP|0.000694756734087544__9362|PRG2|0.000241396385243872__6922|MBL2|0.000378460624408039__ 0 0 0 0 0 5041 18539342 5560 12436 6925 MBP MBP MBP 0 1.9 MBP immunostaining was performed on the coronal and NAWM sections 1 JUMiner_v2.2 1 0 0 2 6925 TotalCon:3<>6925|MBP|4155|Complete__9362|PRG2|5553|Complete__6922|MBL2|4153|Complete__<>AvaiableGeneRif=3<>BEST:6925|MBP|0.000694756734087544<>ScoreDetail__6925|MBP|0.000694756734087544__9362|PRG2|0.000241396385243872__6922|MBL2|0.000378460624408039__ 0 0 0 0 0 5042 18539342 5561 13668 7315 MS4A1 CD20 CD20 17 1.0 5_amp_#xa0 _amp_#x3bc m-thick consecutive sections with antibodies to HLA-DR CD3 CD20 CD68 VCAM-1 and CD138 1 JUMiner_v2.2 1 0 0 2 7315 TotalCon:2<>7315|MS4A1|931|Complete__20412|KRT20|54474|Complete__<>AvaiableGeneRif=2<>BEST:7315|MS4A1|0.00186799501867995<>ScoreDetail__7315|MS4A1|0.00186799501867995__20412|KRT20|0.00109955559627984__ 0 0 0 0 0 5043 18539342 5561 3901 1693 CD68 CD68 CD68 18 0.6 _amp_#x3bc m-thick consecutive sections with antibodies to HLA-DR CD3 CD20 CD68 VCAM-1 and CD138 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5044 18539342 5561 23886 12663 VCAM1 VCAM-1 VCAM-1 19 0.9 m-thick consecutive sections with antibodies to HLA-DR CD3 CD20 CD68 VCAM-1 and CD138 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5045 18539342 5561 19541 10658 SDC1 CD138 CD138 21 1.0 sections with antibodies to HLA-DR CD3 CD20 CD68 VCAM-1 and CD138 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5046 18539342 5562 3901 1693 CD68 CD68 CD68 9 0.6 On NAWM tissue blocks only antibodies to HLA-DR and CD68 were used 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5047 18539342 5566 19329 10524 SALL1 TBS TBS 3 0.0 After washing with TBS the sections were incubated at room temperature for 30_amp_#xa0 min 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5048 18539342 5569 3901 1693 CD68 CD68 CD68 9 0.6 Double immunostaining was performed with antibodies to HLA-DR and CD68 in order to identify a possible colocalization of these antigens 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5049 18539342 5571 3901 1693 CD68 CD68 CD68 4 0.6 First peroxidase labeling for CD68 was visualized with 10% 3 3-diaminobenzidine then immunohistochemistry for HLA-DR 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5050 18539342 5571 23936 12693 VIP VIP VIP 29 0.0 normal serum and peroxidase labeling for HLA-DR was visualized with VIP red (Vector Vector Laboratories Burlingame USA 1 JUMiner_v2.2 1 0 0 2 23228 TotalCon:2<>12693|VIP|7432|Complete__23228|CPAMD8|27151|Complete__<>AvaiableGeneRif=2<>BEST:23228|CPAMD8|0.000974870017331023<>ScoreDetail__23228|CPAMD8|0.000974870017331023__12693|VIP|0.000559874556408352__ 0 0 0 0 0 5051 18539342 5578 3901 1693 CD68 CD68 CD68 26 0.6 study ( Kutzelnigg et al. 2005 based on HLA-DR and CD68 immunostaining presence of microglia nodules and presence of perivascular inflammatory 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5052 18539342 5580 13668 7315 MS4A1 CD20 CD20 4 1.0 Immunostaining for HLA-DR CD3 CD20 CD68 VCAM-1 and CD138 in the CP was evaluated on 1 JUMiner_v2.2 1 0 0 2 7315 TotalCon:2<>7315|MS4A1|931|Complete__20412|KRT20|54474|Complete__<>AvaiableGeneRif=2<>BEST:7315|MS4A1|0.00186799501867995<>ScoreDetail__7315|MS4A1|0.00186799501867995__20412|KRT20|0.00109955559627984__ 0 0 0 0 0 5053 18539342 5580 3901 1693 CD68 CD68 CD68 5 0.6 Immunostaining for HLA-DR CD3 CD20 CD68 VCAM-1 and CD138 in the CP was evaluated on a 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5054 18539342 5580 23886 12663 VCAM1 VCAM-1 VCAM-1 6 0.9 Immunostaining for HLA-DR CD3 CD20 CD68 VCAM-1 and CD138 in the CP was evaluated on a semiquantitative 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5055 18539342 5580 19541 10658 SDC1 CD138 CD138 8 1.0 Immunostaining for HLA-DR CD3 CD20 CD68 VCAM-1 and CD138 in the CP was evaluated on a semiquantitative basis scoring 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5056 18539342 5583 20996 11179 SOD1 ALS ALS 11 0.0 the number of epiplexus cells between MS brains and ALS/control ALS control brains were assessed with a two-tailed T test using 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5057 18539342 5596 20996 11179 SOD1 ALS ALS 21 0.0 on routine hematoxylin_amp_#x2013 eosin staining if compared to viral encephalitis ALS or control brains 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5058 18539342 5600 20996 11179 SOD1 ALS ALS 18 0.0 0.71 cells/field, cells field range 0.2_amp_#x2013 1.4 if compared to ALS and control brains (mean mean 0.06 cells/field, cells field range 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5059 18539342 5610 11629 6493 LAMC2 CSF CSF 12 0.3 staining was also observed on epiplexus cells apposed to the CSF side of the CP epithelium ( Fig 1 E 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5060 18539342 5612 20996 11179 SOD1 ALS ALS 1 0.0 In ALS brains and in normal controls only extremely rare HLA-DR positive 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5061 18539342 5614 3901 1693 CD68 CD68 CD68 0 0.6 CD68 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5062 18539342 5615 3901 1693 CD68 CD68 CD68 3 0.6 In MS CP CD68 staining was observed mainly on round or oval cells located 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5063 18539342 5616 3901 1693 CD68 CD68 CD68 7 0.6 Several epiplexus cells were also stained with CD68 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5064 18539342 5617 3901 1693 CD68 CD68 CD68 0 0.6 CD68 staining pattern in acute viral encephalitis was similar to that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5065 18539342 5618 3901 1693 CD68 CD68 CD68 3 0.6 Only very rare CD68 stained cells were observed in the CP in ALS or 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5066 18539342 5618 20996 11179 SOD1 ALS ALS 12 0.0 rare CD68 stained cells were observed in the CP in ALS or control brains these were mainly round cells in the 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5067 18539342 5620 3901 1693 CD68 CD68 CD68 0 0.6 HLA-DR/CD68 HLA-DR CD68 double immunostaining 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5068 18539342 5621 3901 1693 CD68 CD68 CD68 5 0.6 Double immunohistochemistry for HLA-DR and CD68 showed a colocalization of HLA-DR on most CD68 positive cells 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5069 18539342 5621 3901 1693 CD68 CD68 CD68 13 0.6 HLA-DR and CD68 showed a colocalization of HLA-DR on most CD68 positive cells ( Fig 2 E and F either in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5070 18539342 5621 3901 1693 CD68 CD68 CD68 51 0.6 cells inside the blood vessels which were only stained with CD68 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5071 18539342 5622 3901 1693 CD68 CD68 CD68 14 0.6 observed in the CP stroma which expressed HLA-DR but not CD68 ( Fig 2 G and H 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5072 18539342 5623 3901 1693 CD68 CD68 CD68 2 0.6 These HLA-DR positive/CD68 positive CD68 negative cells often showed a perivascular location 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5073 18539342 5624 3901 1693 CD68 CD68 CD68 8 0.6 In viral encephalitis HLA-DR colocalized almost always with CD68 unlike in MS only very few cells in the CP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5074 18539342 5624 3901 1693 CD68 CD68 CD68 22 0.6 few cells in the CP stroma were HLA-DR positive/CD68 positive CD68 negative ( Fig 3 A and B 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5075 18539342 5629 20996 11179 SOD1 ALS ALS 11 0.0 CD3 positive T cell was detected in the CP in ALS brains and in normal controls 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5076 18539342 5631 13668 7315 MS4A1 CD20 CD20 0 1.0 CD20 1 JUMiner_v2.2 1 0 0 2 7315 TotalCon:2<>7315|MS4A1|931|Complete__20412|KRT20|54474|Complete__<>AvaiableGeneRif=2<>BEST:7315|MS4A1|0.00186799501867995<>ScoreDetail__7315|MS4A1|0.00186799501867995__20412|KRT20|0.00109955559627984__ 0 0 0 0 0 5077 18539342 5632 13668 7315 MS4A1 CD20 CD20 1 1.0 No CD20 positive B cell was observed in the CP in any 1 JUMiner_v2.2 1 0 0 2 7315 TotalCon:2<>7315|MS4A1|931|Complete__20412|KRT20|54474|Complete__<>AvaiableGeneRif=2<>BEST:7315|MS4A1|0.00186799501867995<>ScoreDetail__7315|MS4A1|0.00186799501867995__20412|KRT20|0.00109955559627984__ 0 0 0 0 0 5078 18539342 5634 23886 12663 VCAM1 VCAM-1 VCAM-1 0 0.9 VCAM-1 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5079 18539342 5635 23886 12663 VCAM1 VCAM-1 VCAM-1 1 0.9 Endothelial VCAM-1 immunostaining was observed in most of the CP vessels in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5080 18539342 5637 23886 12663 VCAM1 VCAM-1 VCAM-1 0 0.9 VCAM-1 staining pattern in acute viral encephalitis was similar to that 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5081 18539342 5638 23886 12663 VCAM1 VCAM-1 VCAM-1 1 0.9 No VCAM-1 immunostaining was detected in the CP in ALS brains and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5082 18539342 5638 20996 11179 SOD1 ALS ALS 9 0.0 No VCAM-1 immunostaining was detected in the CP in ALS brains and in normal controls ( Fig 3 G 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5083 18539342 5640 19541 10658 SDC1 CD138 CD138 0 1.0 CD138 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5084 18539342 5641 19541 10658 SDC1 CD138 CD138 2 1.0 Very rare CD138 stained plasma cells were observed in the CP in 3 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5085 18539342 5642 19541 10658 SDC1 CD138 CD138 1 1.0 No CD138 stained cells were observed in encephalitis ALS and control brains 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5086 18539342 5642 20996 11179 SOD1 ALS ALS 8 0.0 No CD138 stained cells were observed in encephalitis ALS and control brains 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5087 18539342 5646 20996 11179 SOD1 ALS ALS 37 0.0 of patients affected by other neurological diseases either non-inflammatory (ALS) ALS or due to direct viral etiology (acute acute viral encephalitis 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5088 18539342 5650 3901 1693 CD68 CD68 CD68 13 0.6 cells in MS CP in this study showed colocalization with CD68 in double immunostaining 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5089 18539342 5651 3901 1693 CD68 CD68 CD68 2 0.6 These HLA-DR positive/CD68 positive CD68 positive cells might presumably be identified as macrophages 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5090 18539342 5652 3901 1693 CD68 CD68 CD68 15 0.6 the CP stroma in MS brains were HLA-DR positive/CD68 positive CD68 negative these might be hypothesized to be dendritic cells as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5091 18539342 5653 3901 1693 CD68 CD68 CD68 22 0.6 material the exact nature and role of HLA-DR positive/CD68 positive CD68 negative cells in MS CP stroma still remain to be 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5092 18539342 5654 3901 1693 CD68 CD68 CD68 1 0.6 HLA-DR positive/CD68 positive CD68 negative cells in the CP stroma were only very rarely 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5093 18539342 5658 11629 6493 LAMC2 CSF CSF 14 0.3 are known to actively gather proteins and metabolites from the CSF and remove them in the peripheral blood ( Nathanson and 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5094 18539342 5658 11629 6493 LAMC2 CSF CSF 42 0.3 in the CP stroma could be therefore well-suited to detect CSF antigens and to present them to peripheral lymphocytes 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5095 18539342 5659 872 583 APC APC APCs 21 0.0 express the necessary costimulatory molecules to act as fully capable APCs 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5096 18539342 5660 872 583 APC APC APCs 6 0.0 It has been hypothesized that the APCs present in the CP after antigen uptake might migrate in 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5097 18539342 5662 3901 1693 CD68 CD68 CD68 34 0.6 in this study by the colocalization of the macrophage marker CD68 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5098 18539342 5663 24053 12728 VWS LPS LPS 8 0.9 Epiplexus cells have been shown to respond to LPS or IFN gamma injection blast injury and other stimuli with 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 5099 18539342 5663 9905 5438 IFNG IFN IFN 10 0.3 Epiplexus cells have been shown to respond to LPS or IFN gamma injection blast injury and other stimuli with ultrastructural modifications 1 JUMiner_v2.2 1 0 0 2 5417 TotalCon:2<>5438|IFNG|3458|Complete__5417|IFNA1|3439|Complete__<>AvaiableGeneRif=2<>BEST:5417|IFNA1|0.000975940127119531<>ScoreDetail__5438|IFNG|0.000736754156687823__5417|IFNA1|0.000975940127119531__ 0 0 0 0 0 5100 18539342 5665 11629 6493 LAMC2 CSF CSF 12 0.3 might be involved in the scavenging of antigens from the CSF and in the production of cytokines chemokines and nitric oxide 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5101 18539342 5665 11629 6493 LAMC2 CSF CSF 24 0.3 in the production of cytokines chemokines and nitric oxide whose CSF levels are increased in MS patients ( Eng-Ang et al. 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5102 18539342 5666 3901 1693 CD68 CD68 CD68 21 0.6 this cell population also expressed the monocyte/macrophage monocyte macrophage marker CD68 but not CD3 or CD20 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5103 18539342 5666 13668 7315 MS4A1 CD20 CD20 26 1.0 the monocyte/macrophage monocyte macrophage marker CD68 but not CD3 or CD20 1 JUMiner_v2.2 1 0 0 2 7315 TotalCon:2<>7315|MS4A1|931|Complete__20412|KRT20|54474|Complete__<>AvaiableGeneRif=2<>BEST:7315|MS4A1|0.00186799501867995<>ScoreDetail__7315|MS4A1|0.00186799501867995__20412|KRT20|0.00109955559627984__ 0 0 0 0 0 5104 18539342 5667 11629 6493 LAMC2 CSF CSF 19 0.3 monocytes on the route from the peripheral blood to the CSF or intraventricular macrophages on the route from the CSF to 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5105 18539342 5667 11629 6493 LAMC2 CSF CSF 28 0.3 the CSF or intraventricular macrophages on the route from the CSF to the peripheral blood ( Eng-Ang et al. 1998 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5106 18539342 5668 19541 10658 SDC1 CD138 CD138-positive 2 1.0 Very rare CD138-positive plasma cells were observed in the stroma of the CP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5107 18539342 5668 20996 11179 SOD1 ALS ALS 26 0.0 the MS brains while these were not observed in encephalitis ALS and control brains 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5108 18539342 5670 23886 12663 VCAM1 VCAM-1 VCAM-1 9 0.9 In MS cases immunostaining for the vascular adhesion molecule VCAM-1 was observed on endothelial cells in most of the CP 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5109 18539342 5671 23886 12663 VCAM1 VCAM-1 VCAM-1 5 0.9 We confirm the lack of VCAM-1 expression on the CP vessels in normal control brains as 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5110 18539342 5672 23886 12663 VCAM1 VCAM-1 VCAM-1 1 0.9 No VCAM-1 immunostaining was observed on the CP epithelial cells differently from 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5111 18539342 5673 23886 12663 VCAM1 VCAM-1 VCAM-1 3 0.9 The expression of VCAM-1 on the CP vessels together with the presence of rare 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5112 18539342 5673 11629 6493 LAMC2 CSF CSF 35 0.3 of the CP for the passage of lymphocyte in the CSF in MS The cellular composition of the CSF in MS 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5113 18539342 5673 11629 6493 LAMC2 CSF CSF 43 0.3 in the CSF in MS The cellular composition of the CSF in MS does not correspond to that of the peripheral 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5114 18539342 5673 11629 6493 LAMC2 CSF CSF 64 0.3 blood suggesting an active regulation of leukocyte trafficking in the CSF ( Engelhardt and Ransohoff 2005 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5115 18539342 5674 11629 6493 LAMC2 CSF CSF 4 0.3 Abnormalities found in MS CSF include increased percentage of T cells higher CD4/CD8 CD4 CD8 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5116 18539342 5674 3865 1678 CD4 CD4 CD4 12 0.6 MS CSF include increased percentage of T cells higher CD4/CD8 CD4 CD8 ratio ( Oreja-Guevara et al. 1998 increased number of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5117 18539342 5674 3870 1706 CD8A CD8 CD8 12 0.3 CSF include increased percentage of T cells higher CD4/CD8 CD4 CD8 ratio ( Oreja-Guevara et al. 1998 increased number of T 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5118 18539342 5674 11629 6493 LAMC2 CSF CSF 52 0.3 B cells and antibody-secreting cells can be found in the CSF of MS patients ( Corcione et al. 2005 Pedemonte et 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5119 18539342 5675 23886 12663 VCAM1 VCAM-1 VCAM-1 3 0.9 The importance of VCAM-1 in this route of lymphocyte entry in the CSF is 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5120 18539342 5675 11629 6493 LAMC2 CSF CSF 12 0.3 of VCAM-1 in this route of lymphocyte entry in the CSF is underscored by the recent observations that therapy with natalizumab 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5121 18539342 5675 23886 12663 VCAM1 VCAM-1 VCAM-1 28 0.9 observations that therapy with natalizumab a monoclonal antibody against the VCAM-1 ligand VLA-4 determines a considerable reduction of the number of 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5122 18539342 5675 11629 6493 LAMC2 CSF CSF 42 0.3 a considerable reduction of the number of lymphocytes in the CSF ( St_amp_#xfc ve et al. 2006 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5123 18539342 5676 11629 6493 LAMC2 CSF CSF 16 0.3 important role of the CP for lymphocyte recruitment in MS CSF other routes of lymphocyte entry might exist such as through 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5124 18539342 5678 20996 11179 SOD1 ALS ALS 27 0.0 was always absent in the control brains and in the ALS brains (in in most of the latter the cause of 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5125 18539342 5679 11629 6493 LAMC2 CSF CSF 22 0.3 entry of lymphocytes in the CNS and for presentation of CSF antigens by APCs in the CP stroma 1 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 5126 18539342 5679 872 583 APC APC APCs 25 0.0 in the CNS and for presentation of CSF antigens by APCs in the CP stroma 13 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5127 18539342 5687 20996 11179 SOD1 ALS ALS 4 0.0 H HLA-DR immunostaining in ALS CP (40X, 40X scale bar = 25_amp_#xa0 _amp_#x3bc m epiplexus 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5128 18539342 5689 3901 1693 CD68 CD68 CD68 1 0.6 2._amp_#xa0 A CD68 immunostaining in MS CP (40X, 40X scale bar = 25_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5129 18539342 5690 3901 1693 CD68 CD68 CD68 2 0.6 B C CD68 immunostaining in MS CP (100X, 100X scale bar = 10_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5130 18539342 5691 3901 1693 CD68 CD68 CD68 4 0.6 D Epiplexus cell showing CD68 immunostaining in ALS CP (100X, 100X scale bar = 10_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5131 18539342 5691 20996 11179 SOD1 ALS ALS 7 0.0 D Epiplexus cell showing CD68 immunostaining in ALS CP (100X, 100X scale bar = 10_amp_#xa0 _amp_#x3bc m 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5132 18539342 5692 3901 1693 CD68 CD68 CD68 4 0.6 E F double immunohistochemistry CD68 (brown)/HLA-DR brown HLA-DR (purple) purple in MS CP showing colocalization 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5133 18539342 5692 3901 1693 CD68 CD68 CD68 13 0.6 brown HLA-DR (purple) purple in MS CP showing colocalization of CD68 and HLA-DR on the cells indicated by arrows (100X, 100X 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5134 18539342 5693 3901 1693 CD68 CD68 CD68 4 0.6 G H double immunohistochemistry CD68 (brown)/HLA-DR brown HLA-DR (purple) purple in MS CP in image 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5135 18539342 5693 3901 1693 CD68 CD68 CD68 19 0.6 CP in image G a photograph was obtained only with CD68 immunostaining subsequently the same microscopic field was photographed (image image 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5136 18539342 5693 3901 1693 CD68 CD68 CD68 55 0.6 as the photographs were obtained from an unmounted section while CD68 positive cells also show HLA-DR immunostaining other cells show only 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5137 18539342 5693 3901 1693 CD68 CD68 CD68 69 0.6 show HLA-DR immunostaining other cells show only HLA-DR and not CD68 immunostaining 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5138 18539342 5694 3901 1693 CD68 CD68 CD68 5 0.6 Fig 3._amp_#xa0 A B double immunohistochemistry CD68 (brown)/HLA-DR brown HLA-DR (purple) purple in viral encephalitis CP in 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5139 18539342 5694 3901 1693 CD68 CD68 CD68 21 0.6 CP in image A a photograph was obtained only with CD68 immunostaining subsequently the same microscopic field was photographed (image image 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5140 18539342 5694 3901 1693 CD68 CD68 CD68 56 0.6 counterstaining as the photographs were obtained from an unmounted section CD68 positive cells also show HLA-DR immunostaining 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5141 18539342 5697 23886 12663 VCAM1 VCAM-1 VCAM-1 1 0.9 E VCAM-1 endothelial immunostaining in MS CP vessels (40X, 40X scale bar 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5142 18539342 5698 23886 12663 VCAM1 VCAM-1 VCAM-1 1 0.9 F VCAM-1 endothelial immunostaining in viral encephalitis CP vessel (40X, 40X scale 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5143 18539342 5699 23886 12663 VCAM1 VCAM-1 VCAM-1 1 0.9 G VCAM-1 immunostaining in ALS CP no endothelial staining is observed (40X, 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 5144 18539342 5699 20996 11179 SOD1 ALS ALS 4 0.0 G VCAM-1 immunostaining in ALS CP no endothelial staining is observed (40X, 40X scale bar 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000548204718954395<>ScoreDetail__5468|IGFALS|0.000378049844417949__11179|SOD1|0.000548204718954395__ 0 0 0 0 0 5145 18539342 5700 19541 10658 SDC1 CD138 CD138 1 1.0 H CD138 positive plasma cell in MS CP (40X, 40X scale bar 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7909 18598679 9075 20996 11179 SOD1 ALS ALS 13 0.8 neuroinflammation is a key event in amyotrophic lateral sclerosis (ALS) ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 7910 18598679 9077 24053 12728 VWS LPS LPS 13 0.0 cord slice cultures we demonstrate that exposure to lipopolysaccharide (LPS) LPS led to the demise of motor neurons in a dose- 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7911 18598679 9080 24053 12728 VWS LPS LPS 5 0.0 NADPH oxidase was activated upon LPS challenge and apocynin the selective inhibitor of this enzyme prevented 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7912 18598679 9080 24053 12728 VWS LPS LPS-induced 36 0.0 play a critical role in motor neuron death caused by LPS-induced inflammation 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7913 18598679 9083 20996 11179 SOD1 ALS ALS 3 0.8 Amyotrophic lateral sclerosis (ALS) ALS is a neurodegenerative disease characterized by the selective degeneration of 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 7914 18598679 9085 20996 11179 SOD1 SOD1 SOD1 4 0.8 Expression of mutant human SOD1 selectively in neurons failed to cause ALS-like disease in mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7915 18598679 9085 20996 11179 SOD1 ALS ALS-like 11 0.8 of mutant human SOD1 selectively in neurons failed to cause ALS-like disease in mice ( Pramatarova et al. 2001 and Lino 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 7916 18598679 9086 20996 11179 SOD1 SOD1 SOD1-expressing 11 0.8 of chimeric mice composed of mixture of wild-type or mutant SOD1-expressing cells suggested that nonneuronal cells influence the fate of spinal 1 JUMiner_v2.2 1 2 32 0 0 0 0 0 0 0 0 7917 18598679 9087 20996 11179 SOD1 SOD1 SOD1 5 0.8 Moreover selective reduction of mutant SOD1 levels in microglia extended survival of transgenic SOD1 G37R mice 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7918 18598679 9087 20996 11179 SOD1 SOD1 SOD1 13 0.8 of mutant SOD1 levels in microglia extended survival of transgenic SOD1 G37R mice ( Boill_amp_#xe9 e et al. 2006 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7919 18598679 9088 20996 11179 SOD1 ALS ALS 15 0.8 cells other than motor neurons play an important role in ALS development 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 7920 18598679 9089 20996 11179 SOD1 ALS ALS 28 0.8 dendritic cells cytokines and chemokines in the spinal cord of ALS patients and mouse models ( Henkel et al. 2004 Alexianu 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 7921 18598679 9090 20996 11179 SOD1 SOD1 SOD1 5 0.8 In addition in the mutant SOD1 G93A transgenic mice inflammatory responses are present before any evidence 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7922 18598679 9091 20996 11179 SOD1 ALS ALS 7 0.8 Analyses of serum skin and muscle from ALS patients indicate widespread inflammatory responses ( Baron et al. 2005 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 7923 18598679 9092 20996 11179 SOD1 SOD1 SOD1 9 0.8 Nguyen et al (2004) 2004 triggered the innate immunity of SOD1 G37R transgenic mice with systemic administration of lipopolysaccharide (LPS), LPS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7924 18598679 9092 24053 12728 VWS LPS LPS 18 0.0 SOD1 G37R transgenic mice with systemic administration of lipopolysaccharide (LPS), LPS and their results demonstrated that repeated LPS injections exacerbated disease 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7925 18598679 9092 24053 12728 VWS LPS LPS 25 0.0 of lipopolysaccharide (LPS), LPS and their results demonstrated that repeated LPS injections exacerbated disease progression 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7926 18598679 9093 20996 11179 SOD1 ALS ALS 15 0.8 an anti-inflammatory compound conferred protection in a mouse model of ALS ( Kriz et al. 2002 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 7927 18598679 9094 20996 11179 SOD1 ALS ALS 14 0.8 that inflammation is a key event in the pathogenesis of ALS and may mediate motor neuron injury 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 7928 18598679 9099 18723 10261 ROS1 ROS ROS 10 0.3 nervous system is particularly vulnerable to reactive oxygen species (ROS) ROS due to its high metabolic rate its deficient oxidant defense 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 7929 18598679 9100 20996 11179 SOD1 ALS ALS 13 0.8 was hold as a common denominator in the pathogenesis of ALS ( Simpson et al. 2003 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 7930 18598679 9101 18723 10261 ROS1 ROS ROS 3 0.3 The source of ROS has generally been attributed to accidental leakage from the electron 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 7931 18598679 9102 18723 10261 ROS1 ROS ROS 5 0.3 However another major source of ROS in the central nervous system is the respiratory burst system 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 7932 18598679 9103 18723 10261 ROS1 ROS ROS 12 0.3 acting as the functional enzyme in the respiratory burst generates ROS not as a byproduct but rather as the primary function 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 7933 18598679 9104 18723 10261 ROS1 ROS ROS 4 0.3 Recent studies indicate that ROS produced by NADPH oxidase could promote neurodegeneration ( Block and 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 7934 18598679 9104 20996 11179 SOD1 ALS ALS 30 0.8 et al. 2005 but the role of NADPH oxidase in ALS remains largely unexplored 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 7935 18598679 9106 24053 12728 VWS LPS LPS 26 0.0 organotypic slice cultures of neonatal rat spinal cords exposed to LPS a surrogate activator of the innate immune system 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7936 18598679 9107 20996 11179 SOD1 ALS ALS 22 0.8 to interneurons which is similar to the pathological change in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 7937 18598679 9107 24053 12728 VWS LPS LPS-mediated 0 0.0 LPS-mediated inflammation induced severe degeneration of motor neurons but relatively slight 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7938 18598679 9125 24053 12728 VWS LPS LPS 6 0.0 The organotypic slices were exposed to LPS in the culture medium at various concentrations (1, 1 10 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7939 18598679 9126 24053 12728 VWS LPS LPS 16 0.0 calcium chelator BAPTA-AM (10_amp_#xa0;_amp_#x3bc;M) 10_amp_#xa0 _amp_#x3bc M was coadministered with LPS (30_amp_#xa0;_amp_#x3bc;g/ml) 30_amp_#xa0 _amp_#x3bc g ml for 2_amp_#xa0 weeks 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7940 18598679 9127 24053 12728 VWS LPS LPS 22 0.0 inhibitor apocynin (0.5 0.5 and 1_amp_#xa0 mM was coapplied with LPS (30_amp_#xa0;_amp_#x3bc;g/ml) 30_amp_#xa0 _amp_#x3bc g ml for 2_amp_#xa0 weeks in the 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7941 18598679 9130 19329 10524 SALL1 TBS TBS 37 0.0 and then rinsed 3 times with Tris buffered saline (TBS) TBS 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7942 18598679 9131 19329 10524 SALL1 TBS TBS 5 0.0 After blocking for 1_amp_#xa0 h in TBS with 10% horse serum cultures were stained overnight at 4_amp_#xa0 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7943 18598679 9131 19329 10524 SALL1 TBS TBS 38 0.0 against calretinin (1:60, 1 60 Santa Cruz CA diluted in TBS containing 0.5% Triton X-100 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7944 18598679 9132 19329 10524 SALL1 TBS TBS 4 0.0 After several washings with TBS containing 0.3% Triton X-100 the cultures were incubated with biotinylated 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7945 18598679 9132 19329 10524 SALL1 TBS TBS 25 0.0 1 1000 or 1 200 Vector Laboratories Burlingame CA in TBS containing 0.3% Triton X-100 for 1_amp_#xa0 h at RT and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7946 18598679 9132 19329 10524 SALL1 TBS TBS 46 0.0 complex reagents (1:200, 1 200 Vector Laboratories Burlingame CA in TBS for 1_amp_#xa0 h at RT 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7947 18598679 9136 24053 12728 VWS LPS LPS 6 0.0 Spinal cord slices treated with 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS for 2weeks and corresponding control slices were randomly selected for 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7948 18598679 9142 14167 7660 NCF1 p47 p47 6 0.9 NADPH oxidase subunits (gp91 gp91 phox p47 phox and IL-1_amp_#x3b2 mRNA expression were evaluated by semiquantitative RT-PCR 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 7949 18598679 9142 8118 4141 GAPDH GAPDH GAPDH 19 1.5 and IL-1_amp_#x3b2 mRNA expression were evaluated by semiquantitative RT-PCR using GAPDH gene as internal standard 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7950 18598679 9152 19573 10691 SDS SDS SDS-polyacrylamide 5 0.0 The samples were electrophoresed on SDS-polyacrylamide gel and the resolved proteins were transferred to polyvinylidene difluoride 11 JUMiner_v2.2 1 0 0 2 10691 TotalCon:2<>10691|SDS|10993|Complete__19440|SBDS|51119|Complete__<>AvaiableGeneRif=2<>BEST:10691|SDS|0.000257997936016512<>ScoreDetail__10691|SDS|0.000257997936016512__19440|SBDS|0.000218026424802686__ 0 0 0 0 0 7951 18598679 9153 14167 7660 NCF1 p47 p47 15 0.9 nonfat dry milk before being probed with primary antibodies to p47 phox (1:200, 1 200 Santa Cruz CA 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 7952 18598679 9168 24053 12728 VWS LPS LPS 1 0.0 Fig 1._amp_#xa0 LPS induced motor neuron injury in organotypic spinal cord slice cultures 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7953 18598679 9169 24053 12728 VWS LPS LPS 18 0.0 culture were treated with medium alone or different concentrations of LPS (1, 1 10 30 60_amp_#xa0;_amp_#x3bc;g/ml) 60_amp_#xa0 _amp_#x3bc g ml for 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7954 18598679 9174 24053 12728 VWS LPS LPS 8 0.0 slice cultures were treated with 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS for 2_amp_#xa0 weeks 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7955 18598679 9177 24053 12728 VWS LPS LPS 7 0.0 (C) C Exposure of spinal cord slices to LPS caused the loss of motor neurons in a dose- and 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7956 18598679 9180 24053 12728 VWS LPS LPS 6 0.0 = 100_amp_#xa0 _amp_#x3bc m 1LPS 1_amp_#xa0;_amp_#x3bc;g/ml 1_amp_#xa0 _amp_#x3bc g ml LPS 10LPS 10_amp_#xa0;_amp_#x3bc;g/ml 10_amp_#xa0 _amp_#x3bc g ml LPS 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7957 18598679 9180 24053 12728 VWS LPS LPS 9 0.0 _amp_#x3bc g ml LPS 10LPS 10_amp_#xa0;_amp_#x3bc;g/ml 10_amp_#xa0 _amp_#x3bc g ml LPS 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 60LPS 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7958 18598679 9180 24053 12728 VWS LPS LPS 12 0.0 _amp_#x3bc g ml LPS 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 60LPS 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7959 18598679 9180 24053 12728 VWS LPS LPS 15 0.0 _amp_#x3bc g ml LPS 60LPS 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7960 18598679 9181 24053 12728 VWS LPS LPS 3 0.0 Fig 2._amp_#xa0 Effect of LPS on interneurons in organotypic spinal cord slice cultures 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7961 18598679 9187 24053 12728 VWS LPS LPS 6 0.0 = 500_amp_#xa0 _amp_#x3bc m 1LPS 1_amp_#xa0;_amp_#x3bc;g/ml 1_amp_#xa0 _amp_#x3bc g ml LPS 10LPS 10_amp_#xa0;_amp_#x3bc;g/ml 10_amp_#xa0 _amp_#x3bc g ml LPS 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7962 18598679 9187 24053 12728 VWS LPS LPS 9 0.0 _amp_#x3bc g ml LPS 10LPS 10_amp_#xa0;_amp_#x3bc;g/ml 10_amp_#xa0 _amp_#x3bc g ml LPS 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 60LPS 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7963 18598679 9187 24053 12728 VWS LPS LPS 12 0.0 _amp_#x3bc g ml LPS 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 60LPS 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7964 18598679 9187 24053 12728 VWS LPS LPS 15 0.0 _amp_#x3bc g ml LPS 60LPS 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7965 18598679 9189 24053 12728 VWS LPS LPS 16 0.0 treated with medium alone or 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS for 2_amp_#xa0 weeks 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7966 18598679 9191 24053 12728 VWS LPS LPS 9 0.0 A and B Interneurons in the control (A) A and LPS (B) B group 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7967 18598679 9192 24053 12728 VWS LPS LPS 1 0.0 After LPS treatment the ultrastructure of interneurons showed little abnormal change compared 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7968 18598679 9193 24053 12728 VWS LPS LPS 10 0.0 and D Motor neurons in the control (C) C and LPS (D) D group 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7969 18598679 9194 24053 12728 VWS LPS LPS 9 0.0 Swollen mitochondria were present in motor neurons exposed to LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7970 18598679 9195 24053 12728 VWS LPS LPS 9 0.0 E and F Microglia in the control (E) E and LPS (F) F group 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7971 18598679 9196 24053 12728 VWS LPS LPS 7 0.0 The cell body of microglia enlarged upon LPS challenge and many lipid droplets and membranous bodies were observed 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7972 18598679 9198 24053 12728 VWS LPS LPS-induced 8 0.0 Fig 4._amp_#xa0 BAPTA-AM afforded a significant neuroprotective effect against LPS-induced cytotoxicity 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7973 18598679 9199 24053 12728 VWS LPS LPS 13 0.0 were treated with medium alone 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS or combination of 10_amp_#xa0 _amp_#x3bc M BAPTA-AM and 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7974 18598679 9199 24053 12728 VWS LPS LPS 21 0.0 10_amp_#xa0 _amp_#x3bc M BAPTA-AM and 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS for 2_amp_#xa0 weeks 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7975 18598679 9202 16489 30306 PHB2 BAP BAP 15 0.5 30LPS-treated slices 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 10_amp_#xa0 BAP LPS 10_amp_#xa0 _amp_#x3bc M BAPTA-AM 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml 1 JUMiner_v2.2 1 0 0 2 30306 TotalCon:2<>24624|SIL1|64374|Complete__30306|PHB2|11331|Complete__<>AvaiableGeneRif=2<>BEST:30306|PHB2|0.000210571844837006<>ScoreDetail__24624|SIL1|0.000130611455108359__30306|PHB2|0.000210571844837006__ 0 0 0 0 0 7976 18598679 9202 24053 12728 VWS LPS LPS 14 0.2 0.01 versus 30LPS-treated slices 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 10_amp_#xa0 BAP LPS 10_amp_#xa0 _amp_#x3bc M BAPTA-AM 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc 5 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7977 18598679 9202 24053 12728 VWS LPS LPS 17 0.1 slices 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 10_amp_#xa0 BAP LPS 10_amp_#xa0 _amp_#x3bc M BAPTA-AM 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 6 JUMiner_v2.2 1 2 lipopolysaccharide 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7978 18598679 9202 24053 12728 VWS LPS LPS 22 0.0 LPS 10_amp_#xa0 _amp_#x3bc M BAPTA-AM 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7979 18598679 9203 14167 7660 NCF1 p47 p47 11 0.9 Changes in the message level of IL-1_amp_#x3b2 gp91 phox and p47 phox in slice cultures after LPS exposure 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 7980 18598679 9203 24053 12728 VWS LPS LPS 17 0.0 IL-1_amp_#x3b2 gp91 phox and p47 phox in slice cultures after LPS exposure 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7981 18598679 9204 24053 12728 VWS LPS LPS 16 0.0 slices treated with medium alone 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS or 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS for 3_amp_#xa0 days 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7982 18598679 9204 24053 12728 VWS LPS LPS 19 0.0 _amp_#x3bc g ml LPS or 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS for 3_amp_#xa0 days after 1_amp_#xa0 week in culture 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7983 18598679 9205 8118 4141 GAPDH GAPDH GAPDH 10 1.5 B Ratio of PCR product from IL-1_amp_#x3b2 to that of GAPDH mRNA 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7984 18598679 9206 14167 7660 NCF1 p47 p47 10 0.9 C Representative bands of NADPH oxidase subunits gp91 phox and p47 phox mRNA expression in slices treated with medium alone or 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 7985 18598679 9206 24053 12728 VWS LPS LPS 22 0.0 treated with medium alone or 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS for 2_amp_#xa0 weeks after 1_amp_#xa0 week in culture 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7986 18598679 9207 14167 7660 NCF1 p47 p47 9 0.9 (D) D Ratio of PCR product from gp91 phox and p47 phox to that of GAPDH mRNA 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 7987 18598679 9207 8118 4141 GAPDH GAPDH GAPDH 14 1.5 product from gp91 phox and p47 phox to that of GAPDH mRNA 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7988 18598679 9208 8118 4141 GAPDH GAPDH GAPDH 0 1.5 GAPDH was used as an internal control 3 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 7989 18598679 9212 24053 12728 VWS LPS LPS-induced 5 0.0 Fig 6._amp_#xa0 NADPH oxidase contributed to LPS-induced toxicity to motor neurons 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7990 18598679 9213 24053 12728 VWS LPS LPS 13 0.0 were treated with medium alone 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS or combination of apocynin (0.5 0.5 or 1_amp_#xa0 mM with 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7991 18598679 9213 24053 12728 VWS LPS LPS 22 0.0 or combination of apocynin (0.5 0.5 or 1_amp_#xa0 mM with LPS (30_amp_#xa0;_amp_#x3bc;g/ml) 30_amp_#xa0 _amp_#x3bc g ml for 2_amp_#xa0 weeks 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7992 18598679 9214 14167 7660 NCF1 p47 p47 3 0.9 Immunoblots (A) A for p47 phox using cytosolic and membranous extracts prepared from the slice 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 7993 18598679 9217 24053 12728 VWS LPS LPS-induced 5 0.0 NADPH oxidase inhibitor apocynin prevented LPS-induced toxicity to motor neurons 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7994 18598679 9222 24053 12728 VWS LPS LPS 21 0.0 0.01 versus 30LPS-treated slices 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 0.5Apo LPS 0.5_amp_#xa0 mM apocynin 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7995 18598679 9222 24053 12728 VWS LPS LPS 24 0.0 30LPS-treated slices 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 0.5Apo LPS 0.5_amp_#xa0 mM apocynin 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 1Apo 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7996 18598679 9222 24053 12728 VWS LPS LPS 29 0.0 0.5Apo LPS 0.5_amp_#xa0 mM apocynin 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 1Apo LPS 1_amp_#xa0 mM apocynin 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7997 18598679 9222 24053 12728 VWS LPS LPS 32 0.0 0.5_amp_#xa0 mM apocynin 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 1Apo LPS 1_amp_#xa0 mM apocynin 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7998 18598679 9222 24053 12728 VWS LPS LPS 37 0.0 1Apo LPS 1_amp_#xa0 mM apocynin 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 7999 18598679 9227 24053 12728 VWS LPS LPS 0 0.0 LPS induced motor neuron cell loss in organotypic spinal cord slices 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8000 18598679 9231 24053 12728 VWS LPS LPS 6 0.0 After treatment with different concentrations of LPS for 1 to 3_amp_#xa0 weeks spinal cord slices were harvested 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8001 18598679 9232 24053 12728 VWS LPS LPS 0 0.0 LPS induced a decrease in the number of surviving motor neurons 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8002 18598679 9233 24053 12728 VWS LPS LPS 11 0.0 showed no significant difference in 1_amp_#xa0;_amp_#x3bc;g/ml 1_amp_#xa0 _amp_#x3bc g ml LPS group compared to the control one at different culture time 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8003 18598679 9234 24053 12728 VWS LPS LPS 4 0.0 After exposure to 10_amp_#xa0;_amp_#x3bc;g/ml 10_amp_#xa0 _amp_#x3bc g ml LPS the number of motor neurons gradually decreased with increasing time 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8004 18598679 9235 24053 12728 VWS LPS LPS 22 0.0 after application of 30 and 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS respectively 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8005 18598679 9240 24053 12728 VWS LPS LPS 7 0.0 treatment with 1 10 and 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS for 1 to 3_amp_#xa0 weeks or treatment with 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8006 18598679 9240 24053 12728 VWS LPS LPS 16 0.0 3_amp_#xa0 weeks or treatment with 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS for 1 to 2_amp_#xa0 weeks the number of interneurons did 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8007 18598679 9241 24053 12728 VWS LPS LPS 6 0.0 Three weeks after exposure to 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS the number of calretinin-positive neurons in the dorsal horns significantly 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8008 18598679 9245 24053 12728 VWS LPS LPS 8 0.0 spinal cord slices treated with 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS for 2_amp_#xa0 weeks the ultrastructure of most neurons in the 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8009 18598679 9248 24053 12728 VWS LPS LPS 15 0.0 motor neurons after treatment with 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS for 2_amp_#xa0 weeks 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8010 18598679 9252 24053 12728 VWS LPS LPS 3 0.0 After treatment with LPS the soma of microglia enlarged evidently and numerous lipid droplets 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8011 18598679 9256 20996 11179 SOD1 ALS ALS 57 0.8 partially responsible for the selective vulnerability of motor neurons in ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 8012 18598679 9258 24053 12728 VWS LPS LPS-mediated 18 0.0 involved in the relative vulnerability of motor neurons induced by LPS-mediated inflammation we coincubated slice cultures with 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8013 18598679 9258 24053 12728 VWS LPS LPS 26 0.0 we coincubated slice cultures with 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS and 10_amp_#xa0 _amp_#x3bc M BAPTA-AM an intracellular Ca 2 chelator 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8014 18598679 9259 24053 12728 VWS LPS LPS 22 0.0 increased in the group with concomitant application of BAPTA-AM and LPS compared to the LPS-only group ( Fig 4 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8015 18598679 9262 24053 12728 VWS LPS LPS 12 0.0 and IL-1_amp_#x3b2 mRNA expression in spinal cord slices treated with LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8016 18598679 9263 24053 12728 VWS LPS LPS 7 0.0 Having demonstrated the concentration-dependent neurotoxicity induced by LPS we next explored early change in the message level of 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8017 18598679 9264 24053 12728 VWS LPS LPS 14 0.0 were exposed to medium alone 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS and 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS for additional 3_amp_#xa0 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8018 18598679 9264 24053 12728 VWS LPS LPS 17 0.0 _amp_#x3bc g ml LPS and 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS for additional 3_amp_#xa0 days 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8019 18598679 9266 24053 12728 VWS LPS LPS 22 0.0 IL-1_amp_#x3b2 was significantly higher in the slice cultures treated with LPS than in normal controls suggesting that there existed inflammatory responses 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8020 18598679 9267 14167 7660 NCF1 p47 p47 13 0.9 the message levels of NADPH oxidase subunits gp91 phox and p47 phox 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 8021 18598679 9268 24053 12728 VWS LPS LPS 6 0.0 Spinal cord slices treated with 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS for 2_amp_#xa0 weeks and corresponding controls were collected for RT-PCR 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8022 18598679 9269 24053 12728 VWS LPS LPS 11 0.0 mRNA expression of gp91 phox in the slices treated with LPS significantly increased compared to the controls ( Figs 5 C 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8023 18598679 9270 14167 7660 NCF1 p47 p47 7 0.9 There was no notable difference in the p47 phox message level between the control and LPS groups ( 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 8024 18598679 9270 24053 12728 VWS LPS LPS 15 0.0 in the p47 phox message level between the control and LPS groups ( Figs 5 C and D 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8025 18598679 9273 16489 30306 PHB2 p22 p22 23 0.5 resting cells composed of two membrane-bound components gp91 phox and p22 phox and several cytosolic components including p47 phox p40 phox 1 JUMiner_v2.2 1 0 0 2 30306 TotalCon:2<>2961|DYNC1H1|1778|Complete__30306|PHB2|11331|Complete__<>AvaiableGeneRif=2<>BEST:30306|PHB2|0.000210571844837006<>ScoreDetail__2961|DYNC1H1|0.000123839009287926__30306|PHB2|0.000210571844837006__ 0 0 0 0 0 8026 18598679 9273 14167 7660 NCF1 p47 p47 31 0.9 gp91 phox and p22 phox and several cytosolic components including p47 phox p40 phox p67 phox and rac1/2 rac1 2 ( 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 8027 18598679 9273 6327 15531 EBNA1BP2 p40 p40 34 0.3 and p22 phox and several cytosolic components including p47 phox p40 phox p67 phox and rac1/2 rac1 2 ( Babior et 1 JUMiner_v2.2 1 0 0 2 682 TotalCon:9<>682|ARHGEF2|9181|Complete__15531|EBNA1BP2|10969|Complete__9565|PSMD7|5713|Complete__6029|IL9|3578|Complete__6508|LANCL1|10314|No_GeneRif__6502|RPSA|3921|Complete__6871|MAPK1|5594|Complete__16896|RABEPK|10244|Complete__15979|TP63|8626|Complete__<>AvaiableGeneRif=8<>BEST:682|ARHGEF2|0.00050178412132025<>ScoreDetail__15979|TP63|0.000362640455519713__16896|RABEPK|7.73993808049536e-05__6502|RPSA|0.000245437510184129__15531|EBNA1BP2|0.000302651424942447__682|ARHGEF2|0.00050178412132025__9565|PSMD7|0.000119075970469159__6029|IL9|0.000345331178956408__6871|MAPK1|0.000417624266367832__ 0 0 0 0 0 8028 18598679 9273 3884 1659 CD33 p67 p67 37 0.0 phox and several cytosolic components including p47 phox p40 phox p67 phox and rac1/2 rac1 2 ( Babior et al. 2002 1 JUMiner_v2.2 1 0 0 2 1659 TotalCon:2<>1659|CD33|945|Complete__16672|METAP2|10988|Complete__<>AvaiableGeneRif=2<>BEST:1659|CD33|0.000604495164038688<>ScoreDetail__1659|CD33|0.000604495164038688__16672|METAP2|0.000526974507608194__ 0 0 0 0 0 8029 18598679 9273 17864 9801 RAC1 RAC1 rac1 41 0.0 components including p47 phox p40 phox p67 phox and rac1/2 rac1 2 ( Babior et al. 2002 14 JUMiner_v2.2 1 1 rac1; 0 0 0 0 0 0 0 0 8030 18598679 9277 24053 12728 VWS LPS LPS-mediated 21 0.0 level and whether it was required for neurotoxicity induced by LPS-mediated inflammation 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8031 18598679 9278 24053 12728 VWS LPS LPS 14 0.0 NADPH oxidase formed an assembled and activated enzyme complex upon LPS challenge 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8032 18598679 9279 14167 7660 NCF1 p47 p47 8 0.9 Two weeks after application of LPS cytosolic subunit p47 phox translocated to the plasma membrane ( Fig 6 A 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 8033 18598679 9279 24053 12728 VWS LPS LPS 5 0.0 Two weeks after application of LPS cytosolic subunit p47 phox translocated to the plasma membrane ( 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8034 18598679 9280 14167 7660 NCF1 p47 p47 17 0.9 oxidase inhibitor apocynin which significantly reduced LPS-induced PHOX cytosolic subunit p47 phox translocation to the cell membrane ( Fig 6 A 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 8035 18598679 9280 24053 12728 VWS LPS LPS-induced 13 0.0 the effect of NADPH oxidase inhibitor apocynin which significantly reduced LPS-induced PHOX cytosolic subunit p47 phox translocation to the cell membrane 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8036 18598679 9283 24053 12728 VWS LPS LPS 7 0.0 In addition exposure of slice cultures to LPS enhanced malondialdehyde production significantly higher than that in the control 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8037 18598679 9284 24053 12728 VWS LPS LPS 5 0.0 Combined application of apocynin with LPS abolished LPS-induced increase in malondialdehyde level ( Fig 6 D 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8038 18598679 9284 24053 12728 VWS LPS LPS-induced 7 0.0 Combined application of apocynin with LPS abolished LPS-induced increase in malondialdehyde level ( Fig 6 D indicating that 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8039 18598679 9287 24053 12728 VWS LPS LPS 8 0.0 In this study we evaluated the consequences of LPS treatment in spinal cord slice cultures 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8040 18598679 9289 24053 12728 VWS LPS LPS 0 0.0 LPS which is a strong activator of innate immunity can lead 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8041 18598679 9291 22217 11848 TLR2 TLR2 TLR2 8 0.6 It has been reported that the expression of TLR2 was upregulated in the spinal cord of mutant SOD1 G37R 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 8042 18598679 9291 20996 11179 SOD1 SOD1 SOD1 17 0.8 of TLR2 was upregulated in the spinal cord of mutant SOD1 G37R transgenic mice ( Nguyen et al. 2004 and MyD88 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 8043 18598679 9291 13937 7562 MYD88 MYD88 MyD88 28 0.3 SOD1 G37R transgenic mice ( Nguyen et al. 2004 and MyD88 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 -SOD1 G37R chimeric mice ( Kang and 14 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 8044 18598679 9291 20996 11179 SOD1 SOD1 SOD1 30 0.8 ( Nguyen et al. 2004 and MyD88 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 -SOD1 G37R chimeric mice ( Kang and Rivest 2007 making it 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 8045 18598679 9291 24053 12728 VWS LPS LPS 46 0.0 Kang and Rivest 2007 making it some reasonable to use LPS as a tool drug 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8046 18598679 9292 22219 11850 TLR4 TLR4 TLR4 10 1.6 Lehnardt et al. (2002) 2002 verified that microglia and its TLR4 is necessary for LPS-induced oligodendrocyte injury 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 8047 18598679 9292 24053 12728 VWS LPS LPS-induced 14 0.0 2002 verified that microglia and its TLR4 is necessary for LPS-induced oligodendrocyte injury 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8048 18598679 9294 24053 12728 VWS LPS LPS 12 0.0 microscopic observation we verified that microglial cells were activated after LPS treatment 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8049 18598679 9295 24053 12728 VWS LPS LPS 12 0.0 IL-1_amp_#x3b2 mRNA level was upregulated in the slices exposure to LPS 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8050 18598679 9296 24053 12728 VWS LPS LPS 4 0.0 These results confirmed that LPS could induce inflammation in organotypic spinal cord slice cultures 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8051 18598679 9297 24053 12728 VWS LPS LPS 4 0.0 Our results showed that LPS exerted significant cytotoxic effects on motor neurons in a dose- 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8052 18598679 9298 20996 11179 SOD1 ALS ALS 33 0.8 showed little change which is similar to the pathology of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 8053 18598679 9298 24053 12728 VWS LPS LPS 6 0.0 Exposure of slice cultures to 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS for 2_amp_#xa0 weeks caused significant decrease in the number of 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8054 18598679 9308 18723 10261 ROS1 ROS ROS 3 0.3 High concentrations of ROS can exert direct toxicity on mitochondria and impair neurons 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 8055 18598679 9309 18723 10261 ROS1 ROS ROS 4 0.3 In addition NADPH oxidase-derived ROS can mediate proinflammatory gene expression and lead to the production 3 JUMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 8056 18598679 9309 7708 3811 FOXG1 QIN Qin 19 0.0 expression and lead to the production of inflammatory cytokines ( Qin et al. 2004 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 8057 18598679 9310 20996 11179 SOD1 ALS ALS 23 0.8 processes both of which are implicated in the pathogenesis of ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 8058 18598679 9312 20996 11179 SOD1 ALS ALS 18 0.8 that NADPH oxidase is up-regulated in the spinal cords of ALS patients and SOD1 G93A transgenic mice ( Wu et al. 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 8059 18598679 9312 20996 11179 SOD1 SOD1 SOD1 21 0.8 is up-regulated in the spinal cords of ALS patients and SOD1 G93A transgenic mice ( Wu et al. 2006 and deletion 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 8060 18598679 9312 14551 7889 NOX1 NOX1 Nox1 35 0.9 mice ( Wu et al. 2006 and deletion of either Nox1 or Nox2 gene significantly slowed disease progression and improved survival 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 8061 18598679 9312 5281 2578 CYBB NOX2 Nox2 37 2.5 Wu et al. 2006 and deletion of either Nox1 or Nox2 gene significantly slowed disease progression and improved survival of ALS 2 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 8062 18598679 9312 20996 11179 SOD1 ALS ALS 47 0.8 Nox2 gene significantly slowed disease progression and improved survival of ALS mice ( Marden et al. 2007 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 8063 18598679 9313 14167 7660 NCF1 p47 p47 29 0.9 gp91 phox mRNA expression and the translocation of cytosolic component p47 phox to the membrane following LPS challenge 1 JUMiner_v2.2 1 1 UserEdit 0 2 9070 TotalCon:4<>10576|CLEC11A|6320|Complete__9070|PLEK|5341|Complete__15912|NSFL1C|55968|No_GeneRif__6062|ING1|3621|Complete__<>AvaiableGeneRif=3<>BEST:9070|PLEK|0.000900776053215078<>ScoreDetail__6062|ING1|0.000637653435357883__10576|CLEC11A|0.000508130081300813__9070|PLEK|0.000900776053215078__ 1 1 10577 6062 ING1 0 8064 18598679 9313 24053 12728 VWS LPS LPS 35 0.0 translocation of cytosolic component p47 phox to the membrane following LPS challenge 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8065 18598679 9314 24053 12728 VWS LPS LPS-induced 2 0.0 More importantly LPS-induced inflammation-mediated toxicity to motor neurons was markedly ameliorated by the 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8066 18598679 9317 24053 12728 VWS LPS LPS 4 0.0 Interestingly low dose of LPS showed a beneficial tendency on motor neuron survival although it 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8067 18598679 9319 24053 12728 VWS LPS LPS 4 0.0 Latest studies demonstrated that LPS preconditioning could induce tolerance to excitotoxic or ischemic brain injury 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8068 18598679 9320 20017 10940 SLC1A2 EAAT2 EAAT2 8 1.0 Corroborating this view are the elevated levels of EAAT2 after exposure to LPS ( Persson et al. 2005 and 1 JUMiner_v2.2 1 0 0 0 0 0 0 0 0 0 8069 18598679 9320 24053 12728 VWS LPS LPS 12 0.0 view are the elevated levels of EAAT2 after exposure to LPS ( Persson et al. 2005 and O'Shea et al. 2006 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8070 18598679 9321 24053 12728 VWS LPS LPS 4 0.0 Could proper doses of LPS protect motor neurons and by which LPS exert neuroprotective potential 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8071 18598679 9321 24053 12728 VWS LPS LPS 11 0.0 proper doses of LPS protect motor neurons and by which LPS exert neuroprotective potential 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8072 18598679 9323 24053 12728 VWS LPS LPS 3 0.0 The concentrations of LPS applied in the present study are relatively high 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8073 18598679 9325 24053 12728 VWS LPS LPS 13 0.0 could reduce the production of inflammatory factors by glia after LPS exposure ( Chang et al. 2000 and astrocytes could prevent 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8074 18598679 9326 24053 12728 VWS LPS LPS 8 0.0 In addition just as what is described above LPS and the products induced by it have pleiotropic functions 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8075 18598679 9327 24053 12728 VWS LPS LPS 20 0.0 cytotoxic effects on NSC-34 neurons dependent on different concentrations of LPS indicating that the equilibrium among various factors determines the function 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8076 18598679 9330 24053 12728 VWS LPS LPS 3 0.0 The contact of LPS a biomacromolecule with high molecular weight with slice cultures may 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8077 18598679 9330 24053 12728 VWS LPS LPS 23 0.0 may be less direct and less sufficient than that of LPS with single cell cultures 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8078 18598679 9331 24053 12728 VWS LPS LPS 11 0.0 midbrain slice cultures 30 or 60_amp_#xa0;_amp_#x3bc;g/ml 60_amp_#xa0 _amp_#x3bc g ml LPS was needed to induce significant dopaminergic neuron injury ( Shibata 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8079 18598679 9333 24053 12728 VWS LPS LPS 7 0.0 Damage induced by a certain concentration of LPS is relatively specific for motor neurons which provide a useful 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8080 18598679 9334 24053 12728 VWS LPS LPS-induced 11 0.0 oxidase contributes to the demise of motor neurons caused by LPS-induced inflammation 1 JUMiner_v2.2 1 0 1 1 0 TotalCon:2<>12728|VWS||No_GeneRif__6121|IRF6|3664|Complete__<>AvaiableGeneRif=1<> 0 0 0 0 0 8081 18598679 9335 20996 11179 SOD1 ALS ALS 23 0.8 and may lead to development of strategies of treatment for ALS 1 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000910039911268296<>ScoreDetail__5468|IGFALS|0.000512229478806505__11179|SOD1|0.000910039911268296__ 0 0 0 0 0 1567 18691039 2340 11629 6493 LAMC2 CSF CSF 3 0.5 Biochemical Markers in CSF of ALS Patients 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 1568 18691039 2340 20996 11179 SOD1 ALS ALS 5 0.1 Biochemical Markers in CSF of ALS Patients 6 JUMiner_v2.2 1 2 amyotrophic lateral sclerosis 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000787252646703788<>ScoreDetail__5468|IGFALS|0.000366372629146352__11179|SOD1|0.000787252646703788__ 0 0 0 0 0 1569 18691039 2341 20996 11179 SOD1 ALS ALS 3 0.0 Amyotrophic lateral sclerosis (ALS) ALS is the most common form of motor neuron diseases (MND) 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000787252646703788<>ScoreDetail__5468|IGFALS|0.000366372629146352__11179|SOD1|0.000787252646703788__ 0 0 0 0 0 1570 18691039 2342 20996 11179 SOD1 ALS ALS 8 0.0 Although several mutations underlying rare cases of familial ALS were identified during the last decade the pathogenesis of ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000787252646703788<>ScoreDetail__5468|IGFALS|0.000366372629146352__11179|SOD1|0.000787252646703788__ 0 0 0 0 0 1571 18691039 2342 20996 11179 SOD1 ALS ALS 18 0.0 ALS were identified during the last decade the pathogenesis of ALS remains poorly understood 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000787252646703788<>ScoreDetail__5468|IGFALS|0.000366372629146352__11179|SOD1|0.000787252646703788__ 0 0 0 0 0 1572 18691039 2344 11629 6493 LAMC2 CSF CSF 14 0.5 related to these pathomechanisms were investigated in cerebrospinal fluid (CSF) CSF 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 1573 18691039 2345 11629 6493 LAMC2 CSF CSF 10 0.5 Although none of these markers gained clinical importance so far CSF might reflect pathophysiological alterations in the course of the disease 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 1574 18691039 2346 11629 6493 LAMC2 CSF CSF 13 0.5 that cellular and proteinchemical processes are better reflected in the CSF than in other body fluids such as blood or urine 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 1575 18691039 2346 11629 6493 LAMC2 CSF CSF 35 0.5 to the proximity of the affected motor neurons to the CSF compartment 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 1576 18691039 2347 11629 6493 LAMC2 CSF CSF 24 0.5 central nervous system may be mirrored in corresponding changes in CSF protein content 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 1577 18691039 2348 11629 6493 LAMC2 CSF CSF 4 0.5 Research on biomarkers in CSF using novel discovery technologies such as proteomics allows to search 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 1578 18691039 2349 11629 6493 LAMC2 CSF CSF 9 0.5 In this review an updated overview is given on CSF biomarkers related to the pathomechanisms supposed to be participating in 3 JUMiner_v2.2 1 2 UserEdit 0 0 0 1 1 0 0 0 1579 18691039 2349 20996 11179 SOD1 ALS ALS 25 0.0 supposed to be participating in the complex disease process of ALS 1 JUMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000787252646703788<>ScoreDetail__5468|IGFALS|0.000366372629146352__11179|SOD1|0.000787252646703788__ 0 0 0 0 0 1888 18715147 2783 18723 10261 ROS1 ROS ROS 6 0.3 The generation of reactive oxygen species (ROS) ROS and reactive nitrogen species (RNS) RNS leads to oxidative and/or 3 SciMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 1889 18715147 2783 6981 22140 FAM20C RNS RNS 11 0.0 reactive oxygen species (ROS) ROS and reactive nitrogen species (RNS) RNS leads to oxidative and/or and or nitrosative damage to cellular 1 SciMiner_v2.2 1 0 0 0 0 0 0 0 0 0 1890 18715147 2784 18723 10261 ROS1 ROS ROS 11 0.3 oxidative stress increases due to an aberrant generation of ROS/RNS ROS RNS and a gradual decline in cellular antioxidant defense mechanisms 3 SciMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 1891 18715147 2784 6981 22140 FAM20C RNS RNS 11 0.3 stress increases due to an aberrant generation of ROS/RNS ROS RNS and a gradual decline in cellular antioxidant defense mechanisms 4 SciMiner_v2.2 1 2 reactive nitrogen species 0 0 0 0 0 0 0 0 1892 18715147 2788 18723 10261 ROS1 ROS ROS 5 0.3 However additional intracellular sources of ROS and RNS exist as well as extracellular sources such as 3 SciMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 1893 18715147 2788 6981 22140 FAM20C RNS RNS 7 0.1 However additional intracellular sources of ROS and RNS exist as well as extracellular sources such as those resulting 6 SciMiner_v2.2 1 2 reactive nitrogen species 0 0 0 0 0 0 0 0 1894 18715147 2789 18723 10261 ROS1 ROS ROS 7 0.3 A significant body of literature indicates that ROS and/or and or RNS resulting from mitochondrial dysfunction neuroinflammation or 3 SciMiner_v2.2 1 2 ros 0 0 0 0 0 0 0 0 1895 18715147 2789 6981 22140 FAM20C RNS RNS 9 0.1 significant body of literature indicates that ROS and/or and or RNS resulting from mitochondrial dysfunction neuroinflammation or toxicants are major factors 6 SciMiner_v2.2 1 2 reactive nitrogen species 0 0 0 0 0 0 0 0 1896 18715147 2789 20996 11179 SOD1 ALS ALS 44 0.0 (AD), AD Huntingtons disease (HD), HD amyotrophic lateral sclerosis (ALS), ALS and many others (1, 1 8 9 16 18 1 SciMiner_v2.2 1 0 0 2 11179 TotalCon:2<>11179|SOD1|6647|Complete__5468|IGFALS|3483|Complete__<>AvaiableGeneRif=2<>BEST:11179|SOD1|0.000707286291639221<>ScoreDetail__5468|IGFALS|6.43107495417859e-05__11179|SOD1|0.000707286291639221__ 0 0 0 0 0 2042 18751914 3073 10437 5992 IL1B IL-1 IL-1 4 1.0 Pro-inflammatory cytokines (TNF-_amp_#945; TNF-_amp_#945 and IL-1 secretory phospholipase A 2 IIA and lipoprotein-PLA 2 are implicated 1 SciMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2043 18751914 3073 22551 11892 TNF TNF TNF-_amp_#945 2 0.1 Pro-inflammatory cytokines (TNF-_amp_#945; TNF-_amp_#945 and IL-1 secretory phospholipase A 2 IIA and lipoprotein-PLA 2 6 SciMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2044 18751914 3071 10437 5992 IL1B IL-1 IL-1 2 1.0 TNF-_amp_#945 and IL-1 alter lipid metabolism and stimulate production of eicosanoids ceramide and 1 SciMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2045 18751914 3071 22551 11892 TNF TNF TNF-_amp_#945 0 0.1 TNF-_amp_#945 and IL-1 alter lipid metabolism and stimulate production of eicosanoids 6 SciMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2046 18751914 3066 14569 7897 NPC1 NPC1 NPC1 26 0.9 Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes resulting in defective cholesterol transport and cholesterol 1 SciMiner_v2.2 1 0 0 0 0 0 0 0 0 0 2047 18751914 3066 14571 14537 NPC2 NPC2 NPC2 28 1.4 C is due to mutations in either the NPC1 or NPC2 genes resulting in defective cholesterol transport and cholesterol accumulation 1 SciMiner_v2.2 1 0 0 0 0 0 0 0 0 0