)| PMID |
15649489 ( ) |
|---|---|
| Title | Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis. |
| Abstract | Accumulating evidence suggests that inflammation plays a major role in the pathogenesis of motoneuron death in amyotrophic lateral sclerosis (ALS) both in humans and transgenic mouse models. Peroxisome proliferator-activated receptors (PPARs) are involved in the inflammatory process. Agonists of PPAR-alpha, -gamma, and -delta show anti-inflammatory effects both in vitro and in vivo. We investigated the therapeutic effect of pioglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, in the G93A SOD1 transgenic mouse model of ALS. Orally administered pioglitazone improved motor performance, delayed weight loss, attenuated motor neuron loss, and extended survival of G93A mice as compared to the untreated control littermate group. Pioglitazone treatment extended survival by 13%, and it reduced gliosis as assessed by immunohistochemical staining for CD-40 and GFAP. Pioglitazone also reduced iNOS, NFkappa-B, and 3-nitrotyrosine immunoreactivity in the spinal cords of G93A transgenic mice. These results suggest that pioglitazone may have therapeutic potential for human ALS. University, New York-Presbyterian Hospital, 525 East 68th Street, Room A-501, New York, NY 10021, USA. mak2026@med.cornell.edu |
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 |
|---|---|---|---|---|
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | 12 | peroxisome proliferator activated receptor gamma | PPAR-G | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 11 | iNOS | nitric oxide synthase | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 10 | superoxide dismutase 1 | SOD1 | |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | 7 | PPARs | PPAR- | |
| 4235 | GFAP | glial fibrillary acidic protein | 7 | glial fibrillary acidic protein | GFAP | |
| 11919 | CD40 | CD40 molecule, TNF receptor superfamily member 5 | 5 | CD-40 | CD40 | |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | 2 | mac 1 | MAC-1 | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 2 | tumor necrosis factor | |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | 1 | nf kappa b | |
| 6081 | INS | insulin | 1 | insulin | |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | 1 | caspase 1 | |
| 1693 | CD68 | CD68 molecule | 1 | CD68 | |
| 11782 | TH | tyrosine hydroxylase | 1 | tyrosine hydroxylase | |
| 1692 | CD63 | CD63 molecule | 1 | CD63 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARs | 2.2 | Peroxisome proliferator-activated receptors (PPARs) PPARs are involved in the inflammatory process |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR- | 2.2 | Agonists of PPAR- -_amp_#x3b3 and -_amp_#x3b4 show anti-inflammatory effects both in vitro and |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-G | 2.2 | the therapeutic effect of pioglitazone a peroxisome proliferator-activated receptor-gamma (PPAR-_amp_#x3b3;) PPAR-_amp_#x3b3 agonist in the G93A SOD1 transgenic mouse model of ALS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | a peroxisome proliferator-activated receptor-gamma (PPAR-_amp_#x3b3;) PPAR-_amp_#x3b3 agonist in the G93A SOD1 transgenic mouse model of ALS |
| 11919 | CD40 | CD40 molecule, TNF receptor superfamily member 5 | CD-40 | 0.3 | and it reduced gliosis as assessed by immunohistochemical staining for CD-40 and GFAP |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | reduced gliosis as assessed by immunohistochemical staining for CD-40 and GFAP |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 3.2 | Pioglitazone also reduced iNOS NF_amp_#x3ba -B and 3-nitrotyrosine immunoreactivity in the spinal cords of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | the gene coding for copper_amp_#x2013 zinc superoxide dismutase 1 (SOD1) SOD1 in a subset of patients with autosomal dominant inherited ALS |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARs | 2.2 | The peroxisome proliferator-activated receptors (PPARs) PPARs are member of the nuclear receptor super family |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARs | 2.2 | PPARs are ligand dependent transcription factors that bind to specific peroxisome |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARs | 2.2 | PPARs have been implicated in insulin sensitivity adipocyte differentiation and inflammatory |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR- | 2.2 | Numerous studies show that agonists of PPAR- -_amp_#x3b3 and -_amp_#x3b4 exert anti-inflammatory effects both in vitro and |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARs | 2.2 | PPARs down-regulate proinflammatory cytokines and iNOS in both macrophages and microglial |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 3.2 | PPARs down-regulate proinflammatory cytokines and iNOS in both macrophages and microglial cells ( Colville-Nash et al. |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-G | 2.2 | Previous studies showed that PPAR-_amp_#x3b3 agonists protect cerebellar granule cells from cytokine-induced apoptotic cell death |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-G | 2.2 | We therefore examined whether an agonist of PPAR-_amp_#x3b3 an anti-inflammatory protein could delay or slow the disease process |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | could delay or slow the disease process in the G93A SOD1 transgenic mouse model of ALS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | Thirty-nine G93A SOD1 transgenic mice were randomly assigned to control (vehicle) vehicle and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | Actos was given in food at 1200 ppm to G93A SOD1 mice ( n = 18 and control mice ( n |
| 11919 | CD40 | CD40 molecule, TNF receptor superfamily member 5 | CD40 | 0.3 | The sections were immunostained with CD40 (Serotec), Serotec GFAP (DAKO), DAKO iNOS (Upstate, Upstate Waltham MA |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | The sections were immunostained with CD40 (Serotec), Serotec GFAP (DAKO), DAKO iNOS (Upstate, Upstate Waltham MA NF_amp_#x3ba B (Santa |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 3.2 | sections were immunostained with CD40 (Serotec), Serotec GFAP (DAKO), DAKO iNOS (Upstate, Upstate Waltham MA NF_amp_#x3ba B (Santa Santa Cruz CA |
| 11919 | CD40 | CD40 molecule, TNF receptor superfamily member 5 | CD40 | 0.3 | G93A mice and controls for immunoreactivity to the microglial marker CD40 and the astrocyte marker GFAP at 110 days of age |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | immunoreactivity to the microglial marker CD40 and the astrocyte marker GFAP at 110 days of age |
| 11919 | CD40 | CD40 molecule, TNF receptor superfamily member 5 | CD40 | 0.3 | Both CD40 and GFAP immunoreactivities were decreased in pioglitazone-treated G93A mice as |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | Both CD40 and GFAP immunoreactivities were decreased in pioglitazone-treated G93A mice as compared to |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 3.2 | iNOS NF_amp_#x3ba -B and nitrotyrosine immunoreactivity |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 3.2 | Control diet fed G93A mice showed strong immunoreactivity for iNOS NF_amp_#x3ba -B and 3-nitrotyrosine |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 3.2 | Pioglitazone treatment reduced the immunoreactivity of iNOS NF_amp_#x3ba -B and 3-nitrotyrosine in the lumbar spinal cord sections |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 3.2 | IL-1_amp_#x3b2 tumor necrosis factor- and iNOS levels are increased in transgenic mouse models of ALS ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | Transcription profiling of the spinal cords of mice with G93A SOD1 mutations showed up-regulation of tumor necrosis factor- CD68 and caspase-1 |
| 1693 | CD68 | CD68 molecule | CD68 | 0.3 | with G93A SOD1 mutations showed up-regulation of tumor necrosis factor- CD68 and caspase-1 mRNA at 11 weeks of age prior to |
| 1692 | CD63 | CD63 molecule | CD63 | 0.3 | Furthermore markers of microgial activation including CD63 MAC-1 cathepsin-5 _amp_#x3b2 2_amp_#xa0 microglobulin C10C- and AGC1Q-_amp_#x3b2 are increased |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | MAC-1 | 1.0 | Furthermore markers of microgial activation including CD63 MAC-1 cathepsin-5 _amp_#x3b2 2_amp_#xa0 microglobulin C10C- and AGC1Q-_amp_#x3b2 are increased at |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-G | 2.2 | It was suggested that these effects were due to PPAR-_amp_#x3b3 activation an increase in inhibitory protein-_amp_#x3ba -_amp_#x3b2 expression and inhibition |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 3.2 | This appears to block iNOS induction and NO-mediated toxicity |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-G | 2.2 | PPAR-_amp_#x3b3 was originally characterized as a regulator of adipocyte differentiation and |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-G | 2.2 | PPAR-_amp_#x3b3 was also shown to have a possible role in cell |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-G | 2.2 | These authors showed anti-inflammatory effect of PPAR-_amp_#x3b3 15d-PGJ 2 in a rat model of carrageenin-induced pleural inflammation |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-G | 2.2 | Our data suggest that the neuroprotective effect of PPAR-_amp_#x3b3 may stem from its role in inflammation however other roles |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-G | 2.2 | stem from its role in inflammation however other roles of PPAR-_amp_#x3b3 may have contributed |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPAR-G | 2.2 | of pioglitazone is not known obviously those cells that express PPAR-_amp_#x3b3 _amp_#xa0 would be targeted |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | The effect of pioglitazone treatment on motor performance in G93A SOD1 transgenic mice from 72 days to 140 days of age |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | ( Pioglitazone-treated G93A mice ( vehicle-treated G93A SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.7 | of pioglitazone treatment on Nissl-stained neuronal cell count in G93A SOD1 transgenic mice at 110 days of age |
| 11919 | CD40 | CD40 molecule, TNF receptor superfamily member 5 | CD40 | 0.3 | Pioglitazone treatment reduced CD40 (marker marker of microglial activation and GFAP (marker marker of |
| 4235 | GFAP | glial fibrillary acidic protein | GFAP | 2.5 | Pioglitazone treatment reduced CD40 (marker marker of microglial activation and GFAP (marker marker of astrocytosis immunoreactivity in the ventral horn of |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 3.2 | Fig 5._amp_#xa0 Pioglitazone treatment reduced iNOS NF_amp_#x3ba -B and 3-nitrotyrosine immunostaining in G93A mice |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 3.2 | Strong iNOS NF_amp_#x3ba -B and 3-nitrotyrosine immunoreactivities in motor neurons (arrow) arrow |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | peroxisome proliferator activated receptor gamma | 1.0 | we investigated the therapeutic effect of pioglitazone a peroxisome proliferator activated receptor gamma ppar _amp_#x3b3; agonist in the g93a sod1 transgenic mouse model of als. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | a major advance in understanding its pathogenesis came from the genetics that identified mutations in the gene coding for copper_amp_#x2013;zinc superoxide dismutase 1 sod1 in a subset of patients with autosomal dominant inherited als rosen et al. 1993 . |
| 6081 | INS | insulin | insulin | 1.0 | ppars have been implicated in insulin sensitivity adipocyte differentiation and inflammatory processes. |
| 11782 | TH | tyrosine hydroxylase | tyrosine hydroxylase | 1.0 | others reported that pioglitazone protected tyrosine hydroxylase th positive substantia nigra neurons from death induced by mptp breidert et al. 2002 and dehmer et al. 2004 . |
| 4235 | GFAP | glial fibrillary acidic protein | glial fibrillary acidic protein | 1.0 | pioglitazone treatment reduced activation of microglia reduced induction of inos positive cells and less glial fibrillary acidic protein positive cells in both striatum and substantia nigra pars compacta of mptp treated mice dehmer et al. 2004 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor | 1.0 | il 1_amp_#x3b2; tumor necrosis factor and inos levels are increased in transgenic mouse models of als almer et al. 1999 elliott 2001 ghezzi et al. 1998 and li et al. 2000 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor | 1.0 | transcription profiling of the spinal cords of mice with g93a sod1 mutations showed up regulation of tumor necrosis factor cd68 and caspase 1 mrna at 11 weeks of age prior to motor neuron death yoshihara et al. 2002 . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | transcription profiling of the spinal cords of mice with g93a sod1 mutations showed up regulation of tumor necrosis factor cd68 and caspase 1 mrna at 11 weeks of age prior to motor neuron death yoshihara et al. 2002 . |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | mac 1 | 1.0 | furthermore markers of microgial activation including cd63 mac 1 cathepsin 5 _amp_#x3b2;2_amp_#xa0;microglobulin c10c and agc1q _amp_#x3b2; are increased at 90 and 120 days of age olsen et al. 2001 . |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | peroxisome proliferator activated receptor gamma | 1.0 | in the present studies we tested the neuroprotective effects of the peroxisome proliferator activated receptor gamma agonist pioglitazone. |
| 4235 | GFAP | glial fibrillary acidic protein | glial fibrillary acidic protein | 1.0 | it reduced induction of inos positive cells and there was less glial fibrillary acidic protein positive cells in both the striatum and substantia nigra pars compacta. |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | nf kappa b | 1.0 | nf kappa b|neuroprotective agents|ppar gamma|thiazolidinediones|pioglitazone|3 nitrotyrosine|tyrosine|nitric oxide synthase|nitric oxide synthase type ii|nos2 protein mouse|sod1 g93a protein|superoxide dismutas |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | nf kappa b|neuroprotective agents|ppar gamma|thiazolidinediones|pioglitazone|3 nitrotyrosine|tyrosine|nitric oxide synthase|nitric oxide synthase type ii|nos2 protein mouse|sod1 g93a protein|superoxide dismutase| |