)| PMID |
17555556 ( ) |
|---|---|
| Title | Mutant SOD1(G93A) microglia are more neurotoxic relative to wild-type microglia. |
| Abstract | Recent studies suggest that microglia over-expressing mutant human superoxide dismutase (mSOD1(G93A)) may contribute to motoneuron death in a transgenic mouse model of familial amyotrophic lateral sclerosis. To further assess the relative neurotoxicity of wild-type microglia, mSOD1(G93A) microglia, and microglia over-expressing wild-type human SOD1, we used primary cultures of microglia and motoneurons in the presence and absence of lipopolysaccharide stimulation. Following activation with lipopolysaccharide, mSOD1(G93A) microglia released more nitric oxide, more superoxide, and less insulin-like growth factor-1 than wild-type microglia. In microglia/motoneuron co-cultures, mSOD1(G93A) microglia induced more motoneuron death and decreased neurite numbers and length compared with wild-type microglia. Mutant SOD1(G93A) microglia also induced more motoneuron injury than microglia over-expressing wild-type human SOD1 in microglia/motoneuron co-cultures. Motoneuron survival was inversely correlated with nitrate + nitrite concentrations in mSOD1(G93A) co-cultures, suggesting the important role of nitric oxide in microglia-induced motoneuron injury. Thus, relative to wild-type microglia, mSOD1(G93A) microglia were more neurotoxic and induced more motoneuron injury than similarly treated wild-type microglia. 77030, USA. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 127 | SOD1 | mSOD1 | SOD | superoxide dismutase | |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | 42 | insulin like growth factor 1 | IGF-1 | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 16 | iNOS | nitric oxide synthase | |
| 11241 | SPI1 | spleen focus forming virus (SFFV) proviral integration oncogene spi1 | 5 | PU.1 | |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 4 | nNOS | neuronal nitric oxide synthase | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 4 | IL-6 | il 6 | |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | 3 | socs 3 | SOCS-3 | |
| 10876 | SIGLEC7 | sialic acid binding Ig-like lectin 7 | 3 | p75 | |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | 2 | socs 1 | SOCS-1 | |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | 2 | Fas | Fas-triggered | |
| 1516 | CAT | catalase | 2 | catalase | |
| 1984 | CISH | cytokine inducible SH2-containing protein | 2 | suppressor of cytokine signaling | SOCS | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 2 | TNF-A | |
| 5992 | IL1B | interleukin 1, beta | 2 | il 1b | IL-1B | |
| 6081 | INS | insulin | 1 | insulin | |
| 25079 | CCDC34 | coiled-coil domain containing 34 | 1 | L-15 | |
| 399 | ALB | albumin | 1 | serum albumin | |
| 9508 | PSEN1 | presenilin 1 (Alzheimer disease 3) | 1 | presenilin 1 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | studies suggest that microglia over-expressing mutant human superoxide dismutase (mSOD1 mSOD1 G93A may contribute to motoneuron death in a transgenic mouse |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Following activation with lipopolysaccharide mSOD1 G93A microglia released more nitric oxide more superoxide and less |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | In microglia/motoneuron microglia motoneuron co-cultures mSOD1 G93A microglia induced more motoneuron death and decreased neurite numbers |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | Mutant SOD1 G93A microglia also induced more motoneuron injury than microglia over-expressing |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | also induced more motoneuron injury than microglia over-expressing wild-type human SOD1 in microglia/motoneuron microglia motoneuron co-cultures |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Motoneuron survival was inversely correlated with nitrate nitrite concentrations in mSOD1 G93A co-cultures suggesting the important role of nitric oxide in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Thus relative to wild-type microglia mSOD1 G93A microglia were more neurotoxic and induced more motoneuron injury |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | human mutant Cu 2 /Zn Zn 2 superoxide dismutase (mSOD1), mSOD1 an animal model of familial ALS immune/inflammatory immune inflammatory changes |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | The selective over-expression of mSOD1 in motoneurons alone does not appear to be sufficient to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | be sufficient to fully reproduce the motoneuron disease observed in mSOD1 mice ( Pramatarova et al 2001 Lino et al 2002 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | In mSOD1 transgenic mice microglial activation is evident prior to the onset |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | An earlier in vivo study with chimeric mice suggested that mSOD1 glia may contribute to motoneuron injury while wild-type glia may |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | by lipopolysaccharide (LPS) LPS up-regulated inducible nitric oxide synthase (iNOS) iNOS expression and released nitric oxide and superoxide which were cytotoxic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11241 | SPI1 | spleen focus forming virus (SFFV) proviral integration oncogene spi1 | PU.1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | (2006) 2006 used the Cre-Lox system to document that reducing mSOD1 expression in mSOD1 G37R microglia also resulted in longer disease |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | the Cre-Lox system to document that reducing mSOD1 expression in mSOD1 G37R microglia also resulted in longer disease duration and survival |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | evidence comparing the relative toxicity of primary microglia cultures from mSOD1 G93A mice with microglia from their wild-type littermates ( Beers |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Our results demonstrate that mSOD1 G93A mouse microglia release more nitric oxide more superoxide and |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | nitric oxide more superoxide and less insulin-like growth factor-1 (IGF-1) IGF-1 than wild-type microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Furthermore mSOD1 G93A microglia induced more motoneuron injury than both wild-type microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Microglial cultures were prepared from 8-day-old mSOD1 G93A mice wt-hSOD1 mice and their non-transgenic littermates as previously |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | The supernatants were collected for nitric oxide and IGF-1 assays and the cells were collected for western analyses |
| 25079 | CCDC34 | coiled-coil domain containing 34 | L-15 | 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 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | The iNOS inhibitor L-N 6 -(1-iminoethyl)lysine - 1-iminoethyl lysine hydrochloride (L-NIL, L-NIL |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 10876 | SIGLEC7 | sialic acid binding Ig-like lectin 7 | p75 | 0.3 | PBS containing 2% horse serum and then with mouse anti-rat p75 LNTR monoclonal antibody (p75, p75 1 800 Chemicon overnight at |
| 10876 | SIGLEC7 | sialic acid binding Ig-like lectin 7 | p75 | 0.3 | and then with mouse anti-rat p75 LNTR monoclonal antibody (p75, p75 1 800 Chemicon overnight at 4_amp_deg C |
| 10876 | SIGLEC7 | sialic acid binding Ig-like lectin 7 | p75 | 0.3 | Motoneuron survival was assessed by direct counting of large p75 positive cells (cell cell bodies > 30 _amp_#x03BC m displaying |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Western blots Wild-type or mSOD1 mouse microglia were incubated at 37_amp_deg C with or without |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | Superoxide assay Superoxide production from microglia was assessed by SOD reduction of ferricytochrome c using a modified protocol of Gao |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | ELISA for IGF-1 Insulin-like growth factor-1 ELISA Duoset kit (R R _amp_ D |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | Minneapolis MN USA was used to determine the concentrations of IGF-1 in cell culture supernatants |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | Mutant SOD1 G93A microglia produce more neurotoxins and less IGF-1 than wild-type |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | Mutant SOD1 G93A microglia produce more neurotoxins and less IGF-1 than wild-type microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | In this study nitric oxide release was compared between primary mSOD1 G93A and wild-type microglia by measuring the nitrate nitrite concentrations |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Although nitrate nitrite concentrations from untreated mSOD1 G93A and wild-type microglia were below the linear range of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | of nitrate nitrite were within the linear range with both mSOD1 G93A and wild-type microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | This represents a 51% increase of nitrate nitrite from mSOD1 G93A microglia compared with wild-type microglia ( p _lt_ 0.05 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | of the cultured microglia we measured the protein levels of iNOS in microglia which is the major source of nitric oxide |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | As demonstrated by western analyses the iNOS expression in untreated microglia was at background levels |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 ( |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | _amp_#x03BC g mL LPS mSOD1 G93A microglia expressed 170% more iNOS than wild-type microglia ( p _lt_ 0.05 ( Fig 1b |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | et al 2004 therefore superoxide levels were compared between primary mSOD1 G93A and wild-type microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Untreated mSOD1 G93A microglia produced 40% more superoxide than wild-type untreated microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | the reduction of ferricytochrome c we added superoxide dismutase (SOD) SOD to the assay to test if the reduction of ferricytochrome |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | The addition of SOD to the assay abolished the reduction of ferricytochrome c suggesting |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | other previous studies demonstrated that microglia produce significant amounts of IGF-1 ( Butovsky et al 2005 Zhao et al 2006 we |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Untreated mSOD1 G93A microglia released 22% less IGF-1 compared with untreated wild-type |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | Untreated mSOD1 G93A microglia released 22% less IGF-1 compared with untreated wild-type microglia ( p _lt_ 0.01 ( |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | mL LPS less IGF-1 was measured in both wild-type and mSOD1 G93A microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | However using either concentrations of LPS mSOD1 G93A microglia released significantly less IGF-1 than wild-type microglia (10 |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | 2.2% in wild-type microglia a 22% decrease in production of IGF-1 p _lt_ 0.05 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Without LPS treatment mSOD1 G93A microglia released significantly more superoxide and less IGF-1 than |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | more superoxide and less IGF-1 than wild-type microglia suggesting that mSOD1 G93A microglia are more activated than wild-type microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | wild-type microglia did not significantly produce more nitric oxide than mSOD1 G93A microglia treated with 10 ng/mL ng mL LPS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | wild-type microglia did not significantly produce more superoxide than untreated mSOD1 G93A microglia |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | presence of 100 times less LPS although the amount of IGF-1 released was small mSOD1 G93A microglia did not release significantly |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | These data demonstrated that mSOD1 G93A microglia are more responsive to stimuli than wild-type microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | Mutant SOD G93A microglia co-cultured with motoneurons produce more nitric oxide and |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | The IGF-1 levels in untreated mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures were |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | The IGF-1 levels in untreated mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures were 14% lower than those |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | However mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures released significantly less IGF-1 (30% |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | Mutant SOD1 G93A microglia induce more motoneuron injury than wild-type microglia Because |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | When co-cultured with motoneurons untreated mSOD1 G93A microglia resulted in 17.9% less motoneuron survival than untreated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | More importantly after treatment with 100-fold less LPS mSOD1 G93A microglia did not significantly alter the number of surviving |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | motoneurons we tested if the addition of an inhibitor of iNOS can rescue motoneurons |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | The addition of the iNOS inhibitor L-NIL (100 100 _amp_#x03BC;g/mL) _amp_#x03BC g mL 1 h |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | L-NIL also partially rescued motoneurons in both mSOD1 G93A and wild-type co-cultures ( Fig 4b |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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% |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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_ |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | Mutant SOD1 G93A microglia are more neurotoxic than wt-hSOD1 microglia Having demonstrated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Therefore mSOD1 G93A microglia induced more motoneuron injury than wt-hSOD1 microglia |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | not observe significant increase of nitric oxide superoxide or less IGF-1 from wt-hSOD1 microglia compared with their littermate controls ( Table |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | 2006 the present in vitro study demonstrates that microglia from mSOD1 G93A transgenic mice were more activated and more responsive to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Additionally when compared with wild-type microglia mSOD1 G93A microglia caused more motoneuron injury in microglia/motoneuron microglia motoneuron |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 0.5 | substances such as nitric oxide superoxide and pro-inflammatory cytokines including TNF-A IL-1B and IL-6 |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.0 | nitric oxide superoxide and pro-inflammatory cytokines including TNF-A IL-1B and IL-6 |
| 5992 | IL1B | interleukin 1, beta | IL-1B | 0.3 | such as nitric oxide superoxide and pro-inflammatory cytokines including TNF-A IL-1B and IL-6 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | leading to further cell damage ( Mhatre et al 2004 iNOS was found to be up-regulated in a transgenic mouse model |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | Up-regulation of iNOS may in turn stimulate nitric oxide production which plays a |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | In the present study we demonstrated that mSOD1 G93A microglia expressed more iNOS and released more nitric oxide |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | present study we demonstrated that mSOD1 G93A microglia expressed more iNOS and released more nitric oxide and superoxide release relative to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | nitrate nitrite produced the fewer motoneurons survived in wild-type or mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | Furthermore pre-treatment with the iNOS inhibitor (L-NIL) L-NIL prior to LPS treatment significantly decreased nitrate |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | Although two earlier reports demonstrated that gene deletion of iNOS or neuronal nitric oxide synthase (nNOS) nNOS does not alter |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | nNOS | 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; |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | nNOS | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | (2007) 2007 demonstrated that mSOD1 G93A mice with both iNOS alleles deleted have a delayed |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | (2007) 2007 demonstrated that mSOD1 G93A mice with both iNOS alleles deleted have a delayed disease progression and a prolonged |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas | 0.6 | Other studies have shown that nitric oxide can induce Fas signaling in mutant SOD1 motoneurons which resulted in mutant SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | shown that nitric oxide can induce Fas signaling in mutant SOD1 motoneurons which resulted in mutant SOD1 motoneuron death but not |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | Fas signaling in mutant SOD1 motoneurons which resulted in mutant SOD1 motoneuron death but not wild-type motoneurons |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | nNOS | 2.2 | Additionally up-regulation of nNOS was required in this Fas-triggered motoneuron death ( Raoul et |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas-triggered | 0.6 | Additionally up-regulation of nNOS was required in this Fas-triggered motoneuron death ( Raoul et al 2002 2006 |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | Among these neurotrophic factors IGF-1 has been shown to have a protective effect on motoneurons |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | IGF-1 is a potent neurotrophic and survival factor ( Vincent et |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | In contrast free IGF-1 levels in ALS patients_amp_#8217 spinal cords and serum were shown |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | al 1998 Wilczak et al 2003 suggesting that down-regulation of IGF-1 trophic support may lead to degeneration of motoneurons |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | IGF-1 has been reported to prevent glutamate-induced embryonic rat spinal cord |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | and delayed disease progression in transgenic ALS mice by enhancing IGF-1 expression in motoneurons |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | A recent study showed that intrathecal injection of IGF-1 into the lumbar spinal cord of transgenic mice expressing the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | spinal cord of transgenic mice expressing the G93A form of mSOD1 delayed the onset of disease and extended survival ( Nagano |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | Following activation with LPS the current study demonstrated that free IGF-1 levels were significantly reduced to 20-30% of untreated controls |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | that wild-type microglia released more free IGF-1 than microglia from mSOD1 G93A transgenic mice either with or without LPS stimulation |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | Therefore more IGF-1 neurotrophic support from wild-type microglia may also contribute to the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Relative to wild-type microglia increased mSOD1 G93A microglial activation induced more motoneuron injury and decreased neurite |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | motoneuron injury and decreased neurite number and length suggesting that mSOD1 G93A microglia are functionally more toxic by releasing more nitric |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | Additionally wild-type microglia may be more neuroprotective by secreting more IGF-1 compared to mSOD1 G93A microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | may be more neuroprotective by secreting more IGF-1 compared to mSOD1 G93A microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | (2004) 2004 found that adult (60 60 days mSOD1 G93A microglia produced significantly more TNF-A and less IL-6 than |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 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 |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.0 | days mSOD1 G93A microglia produced significantly more TNF-A and less IL-6 than wild-type microglia after LPS treatment |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | data is consistent with their results and showed that neonatally-derived mSOD1 G93A microglia released more nitric oxide more superoxide and less |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | G93A microglia released more nitric oxide more superoxide and less IGF-1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | In addition we further provide evidence that mSOD1 G93A microglia are more neurotoxic than wild-type microglia in microglia/motoneuron |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.8 | a heightened sensitivity to LPS as demonstrated by superinduction of iNOS and activation of mitogen-activated protein kinase |
| 11241 | SPI1 | spleen focus forming virus (SFFV) proviral integration oncogene spi1 | PU.1 | 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 |
| 11241 | SPI1 | spleen focus forming virus (SFFV) proviral integration oncogene spi1 | PU.1 | 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 |
| 11241 | SPI1 | spleen focus forming virus (SFFV) proviral integration oncogene spi1 | PU.1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11241 | SPI1 | spleen focus forming virus (SFFV) proviral integration oncogene spi1 | PU.1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | prolonged disease duration and survival when compared with mice receiving mSOD1 G93A microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | (2006) 2006 used transgenic mice with a different SOD1 mutation mSOD1 G37R and a different technique to reduce the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | (2006) 2006 used transgenic mice with a different SOD1 mutation mSOD1 G37R and a different technique to reduce the expression of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | to reach a similar conclusion namely that the reduction of mSOD1 in microglia prolonged disease duration and survival |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | of disease may be more related to the expression of mSOD1 in motoneurons while in accord with our data duration of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | data duration of disease may be related to expression of mSOD1 in microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | wild-type microglia either by the reduction or the elimination of mSOD1 expression are less toxic in vivo |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Because wt-hSOD1 is another control for the neurotoxicity of mSOD1 G93A we compared the relative neurotoxicity of wt-hSOD1 expressing microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | the relative neurotoxicity of wt-hSOD1 expressing microglia to that of mSOD1 G93A expressing microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | extent of neurotoxicity was significantly less than that mediated by mSOD1 G93A microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Furthermore unlike mSOD1 G93A microglia wt-hSOD1 microglia produce similar amounts of nitric oxide |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | wt-hSOD1 microglia produce similar amounts of nitric oxide superoxide and IGF-1 compared with their wild-type littermates |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | When backcrossed into mSOD1 mice the disease progresses more rapidly in these double transgenic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | The reasons that mSOD1 G93A microglia are more activated and more responsive to LPS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Firstly over-expressing mSOD1 may impair the self-feedback systems in microglia and regulate activation |
| 1984 | CISH | cytokine inducible SH2-containing protein | SOCS | 1.6 | For example the suppressor of cytokine signaling (SOCS) SOCS group of proteins has been implicated in a negative feedback |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | SOCS-1 | 2.5 | SOCS-1 and SOCS-3 are critical factors down-regulating the toxic effects of |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 2.5 | SOCS-1 and SOCS-3 are critical factors down-regulating the toxic effects of |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 2.5 | SOCS-1 and SOCS-3 are critical factors down-regulating the toxic effects of LPS ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | al 2002 and may well influence the toxic effects of mSOD1 microglia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Secondly mSOD1 may lead to microglial activation either by directly stimulating the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | on chromogranin-mediated secretion of misfolded mutant SOD1 but not wild-type SOD1 from cells and extracellular mutant SOD1 could trigger microgliosis ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | SOD1 but not wild-type SOD1 from cells and extracellular mutant SOD1 could trigger microgliosis ( Urushitani et al 2005 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | In summary we demonstrate that microglia from mSOD1 G93A transgenic mice are more activated and more responsive to |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | IGF-1 | 1.2 | mice by producing more nitrite oxide and superoxide and less IGF-1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Relative to wild-type microglia mSOD1 G93A microglia may gain modulatory mechanisms that enhance microglial activation |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | neurotoxic substances and the decreased production of neurotrophic molecules by mSOD1 G93A microglia may enhance neurotoxicity or lessen neuroprotection |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | recent studies suggest that microglia over expressing mutant human superoxide dismutase msod1 g93a may contribute to motoneuron death in a transgenic mouse model of familial amyotrophic lateral sclerosis. |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | insulin like growth factor 1 | 1.0 | following activation with lipopolysaccharide msod1 g93a microglia released more nitric oxide more superoxide and less insulin like growth factor 1 than wild type microglia. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | in transgenic mice over expressing human mutant cu 2+ /zn 2+ superoxide dismutase msod1 an animal model of familial als immune/inflammatory changes have been observed at early symptomatic stages almer et al 1999 ; alexianu et al 2001 ; henkel et al 2006 further suggesting a role f |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | our previous in vitro studies have demonstrated that primary microglia activated by lipopolysaccharide lps up regulated inducible nitric oxide synthase inos expression and released nitric oxide and superoxide which were cytotoxic to co cultured primary motoneurons le et al 2001 ; zhao et al 2004 . |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | insulin like growth factor 1 | 1.0 | our results demonstrate that msod1 g93a mouse microglia release more nitric oxide more superoxide and less insulin like growth factor 1 igf 1 than wild type microglia. |
| 399 | ALB | albumin | serum albumin | 1.0 | the cells were collected and centrifuged through a 4% bovine serum albumin cushion at 450 g for 10 min. |
| 6081 | INS | insulin | insulin | 1.0 | the cells were then re suspended in the l 15 culture medium supplemented with sodium bicarbonate 0.2% glucose 3.6 mg/ml progesterone 20 nmol/l insulin 5 _amp_#x03bc;g/ml putrescine 0.1 mmol/l conalbumin 0.1 mg/ml sodium selenite 30 nmol/l penicillin 100 iu/ml streptomycin 100 _amp_#x03bc;g/ml and horse serum 2% . |
| 1516 | CAT | catalase | catalase | 1.0 | to each well 800 nmol/l phorbol 12 myristate 13 acetate 10 u/ml catalase and 80 _amp_#x03bc;mol/l ferricytochrome c in 200 _amp_#x03bc;l hanks_amp_#8217; balanced salt solution was added. |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | insulin like growth factor 1 | 1.0 | elisa for igf 1 insulin like growth factor 1 elisa duoset kit r _amp_ d systems minneapolis mn usa was used to determine the concentrations of igf 1 in cell culture supernatants. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | because superoxide production from the microglia is assayed by the reduction of ferricytochrome c we added superoxide dismutase sod to the assay to test if the reduction of ferricytochrome c is due to superoxide. |
| 5464 | IGF1 | insulin-like growth factor 1 (somatomedin C) | insulin like growth factor 1 | 1.0 | insulin like growth factor 1 is a potent motoneuron trophic and survival factor. |
| 5992 | IL1B | interleukin 1, beta | il 1b | 1.0 | microglial activation can be associated with increased production of potentially cytotoxic substances such as nitric oxide superoxide and pro inflammatory cytokines including tnf a il 1b and il 6. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | microglial activation can be associated with increased production of potentially cytotoxic substances such as nitric oxide superoxide and pro inflammatory cytokines including tnf a il 1b and il 6. |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | neuronal nitric oxide synthase | 1.0 | although two earlier reports demonstrated that gene deletion of inos or neuronal nitric oxide synthase nnos does not alter motoneuron disease in double transgenic inos _amp_#8722;/_amp_#8722; /msod1 g93a or nnos _amp_#8722;/_amp_#8722; /msod1 g93a mice facchinetti et al 1999 ; son et al 2001 a recent |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | 2004 found that adult 60 days msod1 g93a microglia produced significantly more tnf a and less il 6 than wild type microglia after lps treatment. |
| 9508 | PSEN1 | presenilin 1 (Alzheimer disease 3) | presenilin 1 | 1.0 | they reported that microglia derived from mutant presenilin 1 mice were more sensitive to lps treatment than wild type microglia; microglia expressing mutant presenilin 1 exhibited a heightened sensitivity to lps as demonstrated by superinduction of inos and activation of mitogen activated protein kinase. |
| 1516 | CAT | catalase | catalase | 1.0 | these results could possibly be related to the increased oxidative stress and increased protein oxidation due to an over expression of h 2 o 2 and the inability of catalase to compensate fullerton et al 1998 . |
| 1984 | CISH | cytokine inducible SH2-containing protein | suppressor of cytokine signaling | 1.0 | for example the suppressor of cytokine signaling socs group of proteins has been implicated in a negative feedback of cytokine release. |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | socs 1 | 1.0 | socs 1 and socs 3 are critical factors down regulating the toxic effects of lps berlato et al 2002 ; nakagawa et al 2002 and may well influence the toxic effects of msod1 microglia. |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | socs 3 | 1.0 | socs 1 and socs 3 are critical factors down regulating the toxic effects of lps berlato et al 2002 ; nakagawa et al 2002 and may well influence the toxic effects of msod1 microglia. |