PPARγ as a therapeutic target in central nervous system diseases

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 (PPAR gamma), has been investigated for its action in ameliorating the development and progression of a number of CNS diseases. PPAR gamma agonists exhibit potent anti-inflammatory effects and appear to have direct neuroprotective actions. PPAR gamma 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. (c) 2006 Elsevier Ltd. All rights reserved.