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.
MeSH terms
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Animals
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Anti-Inflammatory Agents / pharmacology*
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Anti-Inflammatory Agents / therapeutic use
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Brain / drug effects*
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Brain / immunology
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Brain / physiopathology
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Brain Diseases / drug therapy*
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Brain Diseases / immunology
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Brain Diseases / physiopathology
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Disease Models, Animal
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Encephalitis / drug therapy*
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Encephalitis / genetics
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Encephalitis / immunology
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology
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Humans
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Inflammation Mediators / antagonists & inhibitors
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Inflammation Mediators / immunology
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Inflammation Mediators / metabolism
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Neuroprotective Agents / pharmacology*
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Neuroprotective Agents / therapeutic use
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PPAR gamma / agonists*
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PPAR gamma / immunology
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PPAR gamma / metabolism
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Transcriptional Activation / drug effects
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Transcriptional Activation / genetics
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Transcriptional Activation / immunology
Substances
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Anti-Inflammatory Agents
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Inflammation Mediators
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Neuroprotective Agents
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PPAR gamma