)| PMID |
16766086 ( ) |
|---|---|
| Title | PPARgamma as a therapeutic target in central nervous system diseases. |
| Abstract | Diseases of the central nervous system present a challenge for the development of new therapeutic agents. Nuclear receptors are ligand-activated transcription factors that have proven to be valuable targets for development of new drugs owing to their ability to directly regulate gene expression. The nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma), has been investigated for its action in ameliorating the development and progression of a number of CNS diseases. PPARgamma agonists exhibit potent anti-inflammatory effects and appear to have direct neuroprotective actions. PPARgamma agonists have been shown to be efficacious in animal models of Alzheimer's disease, stroke, multiple sclerosis, Parkinson's disease and amyotrophic lateral sclerosis. The availability of FDA-approved agonists of this receptor will facilitate the rapid translation of these findings into clinical trials for a number of CNS diseases. 44106-4928, United States. |
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 |
|---|---|---|---|---|
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 9 | iNOS | nitric oxide synthase | |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | 8 | COX-2 | cox 2 | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 7 | APP | amyloid | hAPP | |
| 6081 | INS | insulin | 3 | insulin | |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | 2 | ap 1 | AP-1 | |
| 933 | BACE1 | beta-site APP-cleaving enzyme 1 | 2 | BACE1 | |
| 14065 | HDAC9 | histone deacetylase 9 | 2 | HDAC | HDACs | |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | 1 | PPARs | |
| 11362 | STAT1 | signal transducer and activator of transcription 1, 91kDa | 1 | STAT1 | |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | 1 | peroxisome proliferator activated receptor gamma | |
| 3373 | EP300 | E1A binding protein p300 | 1 | p300 | |
| 6207 | JUP | junction plakoglobin | 1 | catenin | |
| 2348 | CREBBP | CREB binding protein (Rubinstein-Taybi syndrome) | 1 | CBP | |
| 17016 | MYST2 | MYST histone acetyltransferase 2 | 1 | histone acetyltransferase | |
| 613 | APOE | apolipoprotein E | 1 | ApoE | |
| 7808 | NGF | nerve growth factor (beta polypeptide) | 1 | nerve growth factor | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARs | 2.5 | subfamily of nuclear receptors are the peroxisome proliferator-activated receptors (PPARs) PPARs which is comprised of three receptors PPAR_amp_#x3b1 _amp_#x3b2;/_amp_#x3b4; _amp_#x3b2 _amp_#x3b4 |
| 14065 | HDAC9 | histone deacetylase 9 | HDACs | 1.3 | complexed with the nuclear corepressors and associated histone deacetylases (HDACs) HDACs ( Fig 1 |
| 14065 | HDAC9 | histone deacetylase 9 | HDAC | 1.3 | keep the receptor in a repressed inactive state while the HDAC maintains the surrounding chromatin in a condensed state through histone |
| 2348 | CREBBP | CREB binding protein (Rubinstein-Taybi syndrome) | CBP | 0.6 | Coactivator proteins like CBP and p300 act to positively regulate gene expression due to |
| 3373 | EP300 | E1A binding protein p300 | p300 | 1.3 | Coactivator proteins like CBP and p300 act to positively regulate gene expression due to their intrinsic |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | AP-1 | 1.3 | the transcriptional level through antagonizing the actions of NF_amp_#x3ba B AP-1 and STAT1 transcription factors ( Daynes and Jones 2002 |
| 11362 | STAT1 | signal transducer and activator of transcription 1, 91kDa | STAT1 | 0.1 | level through antagonizing the actions of NF_amp_#x3ba B AP-1 and STAT1 transcription factors ( Daynes and Jones 2002 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | (1999) 1999 reported that PPAR_amp_#x3b3 agonists suppress cytokine evoked neuronal iNOS expression in vitro thereby preventing NO-mediated cell death of neurons |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | cerebellum resulted in induction of inducible nitric oxide synthase (iNOS) iNOS expression and subsequent neuronal death |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | it was argued to be due to the suppression of iNOS and other inflammatory gene expression ( Heneka et al. 2000 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | However PPAR_amp_#x3b3 agonist treatment was shown to suppress neuronal iNOS expression ( Heneka et al. 1999 |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | demonstrated in studies of hippocampal neurons challenged with neurotoxic beta amyloid (A_amp_#x3b2;) A_amp_#x3b2 peptides ( Inestrosa et al. 2005 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | These agents suppressed cytokine as well as COX-2 expression |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.3 | 1997 treated 1-year-old Tg2576 mice bearing a mutant form of APP (KM670/671NL) KM670 671NL for 4 months with oral pioglitazone or |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | hAPP | 0.3 | Mice overexpressing the hAPP V717I mutation were treated for 7 days with a higher |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.3 | ability of inflammatory cyokines to stimulate the expression of the APP processing enzyme BACE1 ( Sastre et al. 2003 |
| 933 | BACE1 | beta-site APP-cleaving enzyme 1 | BACE1 | 0.5 | cyokines to stimulate the expression of the APP processing enzyme BACE1 ( Sastre et al. 2003 |
| 933 | BACE1 | beta-site APP-cleaving enzyme 1 | BACE1 | 0.5 | to the ability of this nuclear receptor to repress the BACE1 gene ( Sastre et al. 2006 |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.3 | reported that PPAR_amp_#x3b3 activation can lead to suppression of cellular APP levels through the stimulation of the ubiquitination and subsequent degradation |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.3 | through the stimulation of the ubiquitination and subsequent degradation of APP ( d_amp_#x2019 Abramo et al. 2005 |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.3 | reduced A_amp_#x3b2 peptide levels and plaque burden observed in pioglitazone-treated APP overexpressing transgenic mice |
| 613 | APOE | apolipoprotein E | ApoE | 0.0 | Importantly the efficacy of drug treatment was related to ApoE genotype |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | Expression of inflammatory genes such as iNOS cyclooxygenase-2 (COX-2), COX-2 proinflammatory cytokines and intercellular adhesion molecule are |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | Expression of inflammatory genes such as iNOS cyclooxygenase-2 (COX-2), COX-2 proinflammatory cytokines and intercellular adhesion molecule are upregulated following stroke |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | is associated with reduced expression of inflammatory mediators such as iNOS COX-2 and IL-1_amp_#x3b2 ( Fig 5 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | associated with reduced expression of inflammatory mediators such as iNOS COX-2 and IL-1_amp_#x3b2 ( Fig 5 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | level troglitazone inhibited pro-inflammatory cytokine expression including IL1_amp_#x3b2 TNF_amp_#x3b1 and iNOS in the spinal cord |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.5 | vehicle treated rats mRNA was reduced by approximately 25% for iNOS 30% for COX-2 and 50% for IL-1_amp_#x3b2 ( n = |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | mRNA was reduced by approximately 25% for iNOS 30% for COX-2 and 50% for IL-1_amp_#x3b2 ( n = 4 for each |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | peroxisome proliferator activated receptor gamma | 1.0 | the type ii nuclear receptor peroxisome proliferator activated receptor gamma ppar_amp_#x3b3; has proven to be an attractive target for treatment of cns disease as agonists of this receptor have been shown to be effective in ameliorating disease related symptomology and pathol |
| 6081 | INS | insulin | insulin | 1.0 | ppar_amp_#x3b3; agonists act principally in adipose tissue to stimulate fatty acid metabolism sensitize tissues to insulin action and modulate blood glucose levels. |
| 17016 | MYST2 | MYST histone acetyltransferase 2 | histone acetyltransferase | 1.0 | coactivator proteins like cbp and p300 act to positively regulate gene expression due to their intrinsic histone acetyltransferase activity. |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | ap 1 | 1.0 | ppar_amp_#x3b3; suppress proinflammatory gene expression at the transcriptional level through antagonizing the actions of nf_amp_#x3ba;b ap 1 and stat1 transcription factors daynes and jones 2002 . |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | similarly the injection of the proinflammatory stimulus lipopolysaccharide into the rat cerebellum resulted in induction of inducible nitric oxide synthase inos expression and subsequent neuronal death. |
| 6207 | JUP | junction plakoglobin | catenin | 1.0 | the protective effect was correlated with a ppar_amp_#x3b3; mediated inhibition of the protein kinase gsk3_amp_#x3b2; and elevation of cellular _amp_#x3b2; catenin levels although it is unclear how these effects were elicited. |
| 7808 | NGF | nerve growth factor (beta polypeptide) | nerve growth factor | 1.0 | interestingly nerve growth factor was shown to increase the expression and activity of ppar_amp_#x3b3; in sympathetic neuron like pc12 cells fuenzalida et al. 2005 and noradrenaline exposure increased ppar_amp_#x3b3; levels in neuron |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | these agents suppressed cytokine as well as cox 2 expression. |
| 6081 | INS | insulin | insulin | 1.0 | specifically they postulate that rosiglitazone improves insulin sensitivity and suppresses serum corticosteroid levels in the transgenic animals. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | expression of inflammatory genes such as inos cyclooxygenase 2 cox 2 proinflammatory cytokines and intercellular adhesion molecule are upregulated following stroke and increasing the level or the activity of these proteins exacerbates injury while antagonism of the ac |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | there is a reduced inflammatory infiltrate in tzd treated rats that is associated with reduced expression of inflammatory mediators such as inos cox 2 and il 1_amp_#x3b2; fig 5 . |
| 6081 | INS | insulin | insulin | 1.0 | an nih sponsored trial is currently testing the ability of pioglitazone to decrease stroke incidence in non diabetic patients with insulin resistance. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | relative to levels in vehicle treated rats mrna was reduced by approximately 25% for inos 30% for cox 2 and 50% for il 1_amp_#x3b2; n = 4 for each group . |