)| PMID |
16120782 ( ) |
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| Title | The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice. |
| Abstract | Amyotrophic lateral sclerosis (ALS) represents a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Because accompanying inflammation may interact with and promote neurodegeneration, anti-inflammatory treatment strategies are being evaluated. Because peroxisome proliferator-activated receptor gamma (PPARgamma) agonists act as potent anti-inflammatory drugs, we tested whether superoxide dismutase (SOD1)-G93A transgenic mice, a mouse model of ALS, benefit from oral treatment with the PPARgamma agonist pioglitazone (Pio). Pio-treated transgenic mice revealed improved muscle strength and body weight, exhibited a delayed disease onset, and survived significantly longer than nontreated SOD1-G93A mice. Quantification of motor neurons of the spinal cord at day 90 revealed complete neuroprotection by Pio, whereas nontreated SOD1-G93A mice had lost 30% of motor neurons. This was paralleled by preservation of the median fiber diameter of the quadriceps muscle, indicating not only morphological but also functional protection of motor neurons by Pio. Activated microglia were significantly reduced at sites of neurodegeneration in Pio-treated SOD1-G93A mice, as were the protein levels of cyclooxygenase 2 and inducible nitric oxide synthase. Interestingly, mRNA levels of the suppressor of cytokine signaling 1 and 3 genes were increased by Pio, whereas both the mRNA and protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected. Bonn, Germany. Neuroscience |
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)) | 51 | SOD1 | superoxide dismutase | |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | 32 | COX-2-generated | cox 2 | |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | 21 | PPAR | |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | 21 | peroxisome proliferator activated receptor gamma | ppar gamma | |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | 18 | socs 3 | SOCS-3 | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 17 | iNOS | nitric oxide synthase | iNOS-derived | |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | 14 | socs 1 | SOCS-1 | suppressor of cytokine signaling 1 | |
| 132 | ACTB | actin, beta | 6 | beta actin | beta-actin | |
| 1984 | CISH | cytokine inducible SH2-containing protein | 4 | suppressor of cytokine signaling | SOCS | |
| 6081 | INS | insulin | 3 | insulin | |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | 3 | CD11b | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 1 | amyloid | |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | 1 | glyceraldehyde 3 phosphate dehydrogenase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | Because peroxisome proliferator-activated receptor gamma (PPAR PPAR gamma agonists act as potent anti-inflammatory drugs we tested whether |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | mouse model of ALS benefit from oral treatment with the PPAR gamma agonist pioglitazone (Pio) Pio |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | whereas both the mRNA and protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | Peroxisome proliferator-activated receptor gamma (PPAR PPAR gamma ligands were developed as oral antidiabetic drugs after the |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | were developed as oral antidiabetic drugs after the discovery that PPAR gamma activation increases insulin sensitivity and normalizes serum glucose levels |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | Beyond their insulin sensitizing and other metabolic actions PPAR gamma ligands exert several other PPAR gamma-dependent and -independent antineoplastic |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 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 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 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 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | human gene encoding for copper/zinc copper zinc superoxide dismutase (SOD1), SOD1 which have been linked to inherited ALS (Gurney Gurney et |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | astrocytes already at an early presymptomatic stage of disease in SOD1 transgenic mice suggests that inflammation may contribute to motor neuron |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | In microglia and macrophages PPAR gamma activation results in inhibition of proinflammatory gene expression through |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.3 | various mechanisms (Landreth Landreth and Heneka 2001 gamma agonists reduce amyloid beta peptide and cytokine mediated neuroinflammation and neurotoxicity in vitro |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | in these studies we tested whether an oral treatment of SOD1 transgenic mice with the PPAR gamma agonist pioglitazone would reduce |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | whether an oral treatment of SOD1 transgenic mice with the PPAR gamma agonist pioglitazone would reduce neuroinflammation protect from motor neuron |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | (The The Jackson Laboratory Bar Harbor ME which harbor human SOD1 with the G93A mutation in high copy number were used |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | ( n = 18 for wt n = 13 for SOD1 and nontreated ( n = 17 for wt n = |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | ( n = 17 for wt n = 22 for SOD1 groups |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | wt n = 13 for wt-Pio n = 10 for SOD1 n = 7 for SOD1-Pio |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | CD11b | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | wt n = 4 for wt-Pio n = 4 for SOD1 n = 5 for SOD1-Pio |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | For the analysis of iNOS and COX-2 100 microg of protein samples was separated in |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | For the analysis of iNOS and COX-2 100 microg of protein samples was separated in 10% SDS |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | onto Immobilon-P polyvinylidene difluoride membranes and stained with a polyclonal iNOS antibody at 1 500 dilution (rabbit rabbit polyclonal antibody to |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | dilution (rabbit rabbit polyclonal antibody to C terminus of murine iNOS Santa Cruz Biotechology Heidelberg Germany or a polyclonal COX-2 antibody |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | murine iNOS Santa Cruz Biotechology Heidelberg Germany or a polyclonal COX-2 antibody at a 1 600 dilution (rabbit rabbit polyclonal antibody |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | dilution (rabbit rabbit polyclonal antibody to synthetic peptide from murine COX-2 Cayman Ann Arbor MI |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | The specificities of the iNOS and COX-2 antibodies have been confirmed by positive controls containing |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | The specificities of the iNOS and COX-2 antibodies have been confirmed by positive controls containing iNOS or |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | and COX-2 antibodies have been confirmed by positive controls containing iNOS or COX-2 protein (data data not shown |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | antibodies have been confirmed by positive controls containing iNOS or COX-2 protein (data data not shown |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | For the analysis of human and mouse SOD1 2 microg of protein samples was separated in 15% SDS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | Stressgen Victoria British Colombia Canada or a rabbit polyclonal anti-mouse SOD1 antibody at 1 5000 dilution (SOD-101; SOD-101 Stressgen |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | The SOD-101 antibody predominantly detected mouse SOD1 but in addition showed minimal cross-reactivity with human SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | mouse SOD1 but in addition showed minimal cross-reactivity with human SOD1 |
| 1984 | CISH | cytokine inducible SH2-containing protein | SOCS | 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 |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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' |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | SOCS-1 | 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 |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 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 |
| 132 | ACTB | actin, beta | beta-actin | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | 5'-TCA-GGA-TAC-CTC-TCT-TGC-TCT-GG-3' were used as housekeeping control for mouse and human SOD1 |
| 1984 | CISH | cytokine inducible SH2-containing protein | SOCS | 1.6 | PCR conditions for SOCS PCR were 32 cycles of denaturation at 95degreeC for 30 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | The SOD1 PCRs were performed using a SYBR Green Jump Start Taq |
| 1984 | CISH | cytokine inducible SH2-containing protein | SOCS | 1.6 | Western blot and SOCS RT-PCR experiments were quantified by determination of band intensities using |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | the calculation of the relative abundancies of mouse and human SOD1 transcripts the differences in C T between beta-actin and SOD1 |
| 132 | ACTB | actin, beta | beta-actin | 0.3 | and human SOD1 transcripts the differences in C T between beta-actin and SOD1 were determined and expressed as x -fold difference |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 |
| 132 | ACTB | actin, beta | beta-actin | 0.3 | SOD1 were determined and expressed as x -fold difference from beta-actin expression using the following equation 2 |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | PPAR gamma ligands suppress microglial activation thereby protecting neurons from inflammation-mediated |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | Coinduction of COX-2 and iNOS were described in several neurodegenerative disorders including ALS |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | Coinduction of COX-2 and iNOS were described in several neurodegenerative disorders including ALS as well |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 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 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | revealed that SOD1-G93A mice ( n = 4 showed elevated COX-2 levels ( Fig 3 b |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | In contrast iNOS was hardly detectable in wild-type but strongly expressed by SOD1-G93A |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | In both cases Pio treatment significantly decreased COX-2 and iNOS expression in SOD1-G93A mice ( n = 4 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | In both cases Pio treatment significantly decreased COX-2 and iNOS expression in SOD1-G93A mice ( n = 4 |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | SOCS-1 | 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 |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 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 |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 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 ( |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | PPAR gamma and neuroinflammation |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | Originally developed as oral antidiabetics agonists of PPAR gamma have been found to exert potent anti-inflammatory effects in |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | SOD1-G93A transgenic mice would benefit from chronic treatment with a PPAR gamma agonist Within the thiazolidinedione class of PPAR gamma agonists |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | with a PPAR gamma agonist Within the thiazolidinedione class of PPAR gamma agonists Pio is the only substance that penetrates the |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | PPAR gamma and microglial activation |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 = |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | the paw grip endurance test p _lt_ 0.001 compared with SOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | n = 5 for wild-type group n = 6 for SOD1 groups and median fiber diameters in the quadriceps muscle ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | wt n = 4 for wt-Pio n = 4 for SOD1 n = 5 for SOD1-Pio at day 90 of life |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | p _lt_ 0.05 and p _lt_ 0.01 compared with Pio-treated SOD1 mice |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | CD11b | 1.0 | activation of astroglia and inflammation markers a Immunofluorescence colabeling of CD11b (green) green and CGRP (red) red in the spinal cord |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | CD11b | 1.0 | by bright-field (blue/black blue black reaction products and green fluorescent CD11b immunohistochemistry (bottom bottom left are shown |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | = 4 for wt and wt-Pio n = 5 for SOD1 and SOD1-Pio and of COX-2 and iNOS Western blots ( |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | wt-Pio n = 5 for SOD1 and SOD1-Pio and of COX-2 and iNOS Western blots ( n = 4 for all |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | = 5 for SOD1 and SOD1-Pio and of COX-2 and iNOS Western blots ( n = 4 for all groups from |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | SOCS-1 | 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 |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 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 |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 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 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | per group are shown p _lt_ 0.001 compared with nontreated SOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | pioglitazone treatment on the expression levels of endogenous and transgenic SOD1 a -d Quantification of mouse SOD1 ( a and human |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | of endogenous and transgenic SOD1 a -d Quantification of mouse SOD1 ( a and human SOD1 ( b mRNA expression levels |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | a -d Quantification of mouse SOD1 ( a and human SOD1 ( b mRNA expression levels and of mouse SOD1 ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | human SOD1 ( b mRNA expression levels and of mouse SOD1 ( c and human SOD1 ( d protein levels in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | expression levels and of mouse SOD1 ( c and human SOD1 ( d protein levels in the spinal cord at day |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | Note the variations in mouse SOD1 expression levels between the groups in a and c |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | treatment does not alter expression levels of endogenous and transgenic SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | Because the expression level of the mutant SOD1 transgene affects the course of disease in SOD1-G93A mice and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | an altered expression of either endogenous mouse or transgenic human SOD1 we determined SOD1 gene expression levels in our mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | of either endogenous mouse or transgenic human SOD1 we determined SOD1 gene expression levels in our mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | for total RNA and protein and both mouse and human SOD1 expression levels were determined using quantitative RT-PCR and Western blotting |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | As shown in Figure 4 neither mouse SOD1 mRNA ( Fig 4 a or protein ( Fig 4 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | a or protein ( Fig 4 c levels nor human SOD1 mRNA ( Fig 4 b or protein ( Fig 4 |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | PPAR gamma-mediated inhibition of inflammatory mediators |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | We found a marked reduction in the expression of COX-2 and iNOS two major proinflammatory enzymes after Pio treatment |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | found a marked reduction in the expression of COX-2 and iNOS two major proinflammatory enzymes after Pio treatment |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 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 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 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 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS-derived | 2.2 | Apart from the detrimental action of either iNOS-derived excess NO or COX-2-generated proinflammatory prostanoids the dual inhibition of |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-generated | 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 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | Thus NO may increase the catalytic activity of COX-2 thereby increasing the production of proinflammatory prostanoids (Nogawa Nogawa et |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | PPAR gamma-mediated activation of anti-inflammatory genes |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | Several PPAR gamma-dependent and -independent anti-inflammatory actions of the TZD class of |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | SOCS-1 | 3.5 | Interestingly SOCS-1 and SOCS-3 have been reported to increase in response to |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 3.5 | Interestingly SOCS-1 and SOCS-3 have been reported to increase in response to |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 3.5 | Interestingly SOCS-1 and SOCS-3 have been reported to increase in response to TZDs in |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | The latter signal transduction pathway is also involved in the iNOS and COX-2 gene regulation after inflammatory stimulation |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | signal transduction pathway is also involved in the iNOS and COX-2 gene regulation after inflammatory stimulation |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | SOCS-1 | 3.5 | Because the ability of SOCS-1 and SOCS-3 to suppress cytokine stimulation has also been confirmed |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 3.5 | Because the ability of SOCS-1 and SOCS-3 to suppress cytokine stimulation has also been confirmed |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 3.5 | Because the ability of SOCS-1 and SOCS-3 to suppress cytokine stimulation has also been confirmed by in |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | SOCS-1 | 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 |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 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 |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | SOCS-3 | 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 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.2 | antagonizing the JAK-STAT pathway contributes to the observed suppression of iNOS and COX-2 expression |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 2.0 | JAK-STAT pathway contributes to the observed suppression of iNOS and COX-2 expression |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | The principal clinical usage of PPAR gamma agonists is for treatment of type II diabetes |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | It has been shown recently that PPAR gamma agonist treatment leads to an upregulation of Cu/Zn-SOD1 Cu |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | of ischemia (Shimazu Shimazu et al. 2005 suggesting that enhanced SOD1 levels may be protective by reducing oxidative stress |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | changes in the expression levels of neither mouse nor human SOD1 in our mice we can rule out that the reported |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | reported effects of chronic Pio treatment result from altered endogenous SOD1 or transgenic SOD1-G93A expression levels |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | neuron death in ALS has been supported by studies on SOD1 transgenic mice reporting protective effects of cyclooxygenase inhibitors (Drachman Drachman |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | conclude that patients suffering from sporadic ALS will benefit from PPAR gamma-agonist treatment if initiated after clinical onset of disease |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 3.3 | before the appearance of clinical symptoms may benefit from prophylactic PPAR gamma-agonist medication |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | antibody and Dr Albrecht Clement (Mainz, Mainz Germany for donating SOD1 antibodies |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | because peroxisome proliferator activated receptor gamma ppar gamma agonists act as potent anti inflammatory drugs we tested whether superoxide dismutase sod1 g93a transgenic mice a mouse model of als benefit from oral treatment with the ppar gamma agonist pioglitazo |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | agonists act as potent anti inflammatory drugs we tested whether superoxide dismutase sod1 g93a transgenic mice a mouse model of als benefit from oral treatment with the ppar gamma agonist pioglitazone pio . |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | peroxisome proliferator activated receptor gamma | 1.0 | because peroxisome proliferator activated receptor gamma ppar gamma agonists act as potent anti inflammatory drugs we tested whether superoxide dismutase sod1 g93a transgenic mice a mouse model of als benefit from oral treatment with the ppar gamma agonist |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | because peroxisome proliferator activated receptor gamma ppar gamma agonists act as potent anti inflammatory drugs we tested whether superoxide dismutase sod1 g93a transgenic mice a mouse model of als benefit from oral treatment with the ppar gamma agonist pioglitazone pio . |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | activated microglia were significantly reduced at sites of neurodegeneration in pio treated sod1 g93a mice as were the protein levels of cyclooxygenase 2 and inducible nitric oxide synthase. |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | suppressor of cytokine signaling 1 | 1.0 | interestingly mrna levels of the suppressor of cytokine signaling 1 and 3 genes were increased by pio whereas both the mrna and protein levels of endogenous mouse sod1 and of transgenic human sod1 remained unaffected. |
| 6081 | INS | insulin | insulin | 1.0 | peroxisome proliferator activated receptor gamma ppar gamma ligands were developed as oral antidiabetic drugs after the discovery that ppar gamma activation increases insulin sensitivity and normalizes serum glucose levels berger and moller 2002 gamma activators of the thiazolidinedione tzd class of antidiabetic drugs. |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | peroxisome proliferator activated receptor gamma ppar gamma ligands were developed as oral antidiabetic drugs after the discovery that ppar gamma activation increases insulin sensitivity and normalizes serum glucose levels berger and moller 2002 gamma activators of the thiazolidinedione tzd class of antidiabetic drugs. |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | peroxisome proliferator activated receptor gamma | 1.0 | peroxisome proliferator activated receptor gamma ppar gamma ligands were developed as oral antidiabetic drugs after the discovery that ppar gamma activation increases insulin sensitivity and normalizes serum glucose levels berger and moller 2002 ga |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | beyond their insulin sensitizing and other metabolic actions ppar gamma ligands exert several other ppar gamma dependent and independent antineoplastic and anti inflammatory effects daynes and jones 2002 ; blanquart et al. 2003 ; grommes et al. 2004 . |
| 6081 | INS | insulin | insulin | 1.0 | beyond their insulin sensitizing and other metabolic actions ppar gamma ligands exert several other ppar gamma dependent and independent antineoplastic and anti inflammatory effects daynes and jones 2002 ; blanquart et a |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | feature of als is the loss of motor neurons talbot 2002 which is accompanied by a robust glial response including activation of microglia and astrocytes as well as the expression of cyclooxygenase 2 cox 2 and nitric oxide synthase inos in the spinal cord phul et al. 2000 ; almer et al. 2001 ; yasojima et al. 2001 ; barbeito et al. 2004 . |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | f als is the loss of motor neurons talbot 2002 which is accompanied by a robust glial response including activation of microglia and astrocytes as well as the expression of cyclooxygenase 2 cox 2 and nitric oxide synthase inos in the spinal cord phul et al. 2000 ; almer et al. 2001 ; yasojima et al. 2001 ; barbeito et al. 2004 . |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | both pathologies motor neuron loss and neuroinflammation can be found in transgenic mice overexpressing mutant variants of the human gene encoding for copper/zinc superoxide dismutase sod1 which have been linked to inherited als gurney et al. 1994 ; hensley et al. 2002 ; yoshihara et al. 2002 ; kunst 2004 . |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | in microglia and macrophages ppar gamma activation results in inhibition of proinflammatory gene expression through various mechanisms landreth and heneka 2001 gamma agonists reduce amyloid beta peptide and cytokine mediated neuroinflammat |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | given the beneficial effects observed in these studies we tested whether an oral treatment of sod1 transgenic mice with the ppar gamma agonist pioglitazone would reduce neuroinflammation protect from motor neuron loss and improve clinical als symptoms. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | for the analysis of inos and cox 2 100 microg of protein samples was separated in 10% sds gels transferred onto immobilon p polyvinylidene difluoride membranes and stained with a polyclonal inos antibody at 1:500 dilution rabbit polyc |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | difluoride membranes and stained with a polyclonal inos antibody at 1:500 dilution rabbit polyclonal antibody to c terminus of murine inos; santa cruz biotechology heidelberg germany or a polyclonal cox 2 antibody at a 1:600 dilution rabbit polyclonal antibody to synthetic peptide from murine cox 2; cayman ann arbor mi . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | antibody at a 1:600 dilution rabbit polyclonal antibody to synthetic peptide from murine cox 2; cayman ann arbor mi . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the specificities of the inos and cox 2 antibodies have been confirmed by positive controls containing inos or cox 2 protein data not shown . |
| 132 | ACTB | actin, beta | beta actin | 1.0 | afterward the blots were stripped and stained with a monoclonal anti beta actin antibody at 1:10 000 dilution sigma aldrich taufkirchen germany . |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | socs 1 | 1.0 | the primers were the following: suppressor of cytokine signaling 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 |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | socs 3 | 1.0 | the primers were the following: suppressor of cytokine signaling 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 reverse 5' cac aac tgg ttc acc gct tg 3'; human sod1 forw |
| 1984 | CISH | cytokine inducible SH2-containing protein | suppressor of cytokine signaling | 1.0 | the primers were the following: suppressor of cytokine signaling 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 |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | socs 1 | 1.0 | glyceraldehyde 3 phosphate dehydrogenase forward 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 as housekeeping control for mouse and human sod1. |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | glyceraldehyde 3 phosphate dehydrogenase | 1.0 | glyceraldehyde 3 phosphate dehydrogenase forward 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 re |
| 132 | ACTB | actin, beta | beta actin | 1.0 | glyceraldehyde 3 phosphate dehydrogenase forward 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 as housekeeping control for mouse and human sod1. |
| 132 | ACTB | actin, beta | beta actin | 1.0 | for the calculation of the relative abundancies of mouse and human sod1 transcripts the differences in c t between beta actin and sod1 were determined and expressed as x fold difference from beta actin expression using the following equation: 2 . |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | ppar gamma ligands suppress microglial activation thereby protecting neurons from inflammation mediated cell death heneka et al. 1999 ~50%. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | coinduction of cox 2 and inos were described in several neurodegenerative disorders including als as well as in the sod1 g93a model used in this study almer et al. 1999 2001 ; sasaki et al. 2001 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | western blot analysis of lumbar spinal cord lysates from 90 d old mice confirmed cox 2 expression in wild type mice n = 4 and revealed that sod1 g93a mice n = 4 showed elevated cox 2 levels fig 3 b . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in both cases pio treatment significantly decreased cox 2 and inos expression in sod1 g93a mice n = 4 . |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | socs 1 | 1.0 | notably this reduction was paralleled by a marked transcriptional upregulation of anti inflammatory socs 1 and socs 3 genes fig 3 c in both pio treated groups n = 5 for all groups . |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | socs 3 | 1.0 | notably this reduction was paralleled by a marked transcriptional upregulation of anti inflammatory socs 1 and socs 3 genes fig 3 c in both pio treated groups n = 5 for all groups . |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | ppar gamma and neuroinflammation |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | originally developed as oral antidiabetics agonists of ppar gamma have been found to exert potent anti inflammatory effects in several models of neuroinflammation landreth and heneka 2001 gamma mediated reduction of inflammation was neuroprotective we hypothesized |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | s of neuroinflammation landreth and heneka 2001 gamma mediated reduction of inflammation was neuroprotective we hypothesized that sod1 g93a transgenic mice would benefit from chronic treatment with a ppar gamma agonist within the thiazolidinedione class of ppar gamma agonists pio is the only substance that penetrates the blood brain barrier to a significant extent maeshiba et al. 1997 and has therefore been |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | agonist within the thiazolidinedione class of ppar gamma agonists pio is the only substance that penetrates the blood brain barrier to a significant extent maeshiba et al. 1997 and has therefore been chosen for treatment experiments. |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | ppar gamma and microglial activation |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | socs 1 | 1.0 | nos western blots n = 4 for all groups from spinal cord samples derived from 90 d old mice b are shown. p _lt_ 0.01 and p _lt_ 0.001 compared with the respective nontreated group. c quantification of socs 1 and socs 3 mrna levels in the spinal cord at day 90 of life n = 5 for all groups . |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | socs 3 | 1.0 | blots n = 4 for all groups from spinal cord samples derived from 90 d old mice b are shown. p _lt_ 0.01 and p _lt_ 0.001 compared with the respective nontreated group. c quantification of socs 1 and socs 3 mrna levels in the spinal cord at day 90 of life n = 5 for all groups . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | quantification of microglia at day 90 of life bottom right; n = 4 for wt and wt pio; n = 5 for sod1 and sod1 pio and of cox 2 and inos western blots n = 4 for all groups from spinal cord samples derived from 90 d old mice b are shown. p _lt_ 0.01 and p _lt_ 0.001 compared with the respective nontreated group. c quantificati |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | ppar gamma mediated inhibition of inflammatory mediators |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | we found a marked reduction in the expression of cox 2 and inos two major proinflammatory enzymes after pio treatment. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | coinduction of both enzymes by several factors including glutamate release and secretion of proinflammatory cytokines may be caused by similar or identical stimulators o'banion 1999 because the cox 2 and inos promoters share several binding sites for signal transduction factors involved in inflammatory signal cascades xie et al. 1993 ; nathan and xie 1994 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | apart from the detrimental action of either inos derived excess no or cox 2 generated proinflammatory prostanoids the dual inhibition of both enzymes observed in response to pio treatment may be advantageous because both pathways mutually increase their pathogenicity. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | thus no may increase the catalytic activity of cox 2 thereby increasing the production of proinflammatory prostanoids nogawa et al. 1998 . |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | ppar gamma mediated activation of anti inflammatory genes |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | several ppar gamma dependent and independent anti inflammatory actions of the tzd class of drugs have been described and suppression of inflammation may be achieved not at a single but at multiple levels including dire |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | socs 1 | 1.0 | interestingly socs 1 and socs 3 have been reported to increase in response to tzds in microglia and astrocytes in vitro which in turn inhibit janus kinase signal transducer and activator of transcription jak stat inflamm |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | socs 3 | 1.0 | interestingly socs 1 and socs 3 have been reported to increase in response to tzds in microglia and astrocytes in vitro which in turn inhibit janus kinase signal transducer and activator of transcription jak stat inflammatory signa |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the latter signal transduction pathway is also involved in the inos and cox 2 gene regulation after inflammatory stimulation. |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | socs 1 | 1.0 | because the ability of socs 1 and socs 3 to suppress cytokine stimulation has also been confirmed by in vivo experiments using knock out mice shouda et al. 2001 ; suzuki et al. 2001 it seems likely that upregulation of socs 1 and |
| 19383 | SOCS1 | suppressor of cytokine signaling 1 | socs 1 | 1.0 | and socs 3 to suppress cytokine stimulation has also been confirmed by in vivo experiments using knock out mice shouda et al. 2001 ; suzuki et al. 2001 it seems likely that upregulation of socs 1 and socs 3 levels in response to pio treatment reflects one mechanism of the anti inflammatory effect observed and antagonizing the jak stat pathway contributes to the observed suppression of inos an |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | socs 3 | 1.0 | because the ability of socs 1 and socs 3 to suppress cytokine stimulation has also been confirmed by in vivo experiments using knock out mice shouda et al. 2001 ; suzuki et al. 2001 it seems likely that upregulation of socs 1 and socs 3 lev |
| 19391 | SOCS3 | suppressor of cytokine signaling 3 | socs 3 | 1.0 | to suppress cytokine stimulation has also been confirmed by in vivo experiments using knock out mice shouda et al. 2001 ; suzuki et al. 2001 it seems likely that upregulation of socs 1 and socs 3 levels in response to pio treatment reflects one mechanism of the anti inflammatory effect observed and antagonizing the jak stat pathway contributes to the observed suppression of inos and cox 2 exp |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | nd socs 3 levels in response to pio treatment reflects one mechanism of the anti inflammatory effect observed and antagonizing the jak stat pathway contributes to the observed suppression of inos and cox 2 expression. |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | the principal clinical usage of ppar gamma agonists is for treatment of type ii diabetes. |
| 6081 | INS | insulin | insulin | 1.0 | the drugs act to enhance insulin sensitivity and normalize blood glucose levels patsouris et al. 2004 gamma in enhancing muscle strength and preserving neuronal integrity and function might also arise from improved glucose utilizati |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | it has been shown recently that ppar gamma agonist treatment leads to an upregulation of cu/zn sod1 expression in a rat model of ischemia shimazu et al. 2005 suggesting that enhanced sod1 levels may be protective by reducing oxidative stress. |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | sing an early anti inflammatory treatment strategy initiated well before the first onset of clinical symptoms does not allow us to conclude that patients suffering from sporadic als will benefit from ppar gamma agonist treatment if initiated after clinical onset of disease. |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | ppar gamma | 1.0 | however it seems possible that in the case of familiar als family members with an inherited als risk which can be diagnosed before the appearance of clinical symptoms may benefit from prophylactic ppar gamma agonist medication. |