Therapeutic use of agonists of the nuclear receptor PPARgamma in Alzheimer's disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disease for which there are no highly effective therapies. A novel therapeutic approach to the treatment of AD is the use of agonists of the nuclear receptor, peroxisome proliferators-activated receptor gamma (PPARgamma). PPARgamma is a ligand activated transcription factor whose best described roles are to regulate lipid metabolism and inflammation. Agonists of PPARgamma have been shown to ameliorate AD-related pathology in animal models of AD and improve cognition. A number of potential mechanisms have been advanced to account for these effects. PPARgamma agonists act as insulin sensitizers, facilitating insulin action. In addition, PPARgamma agonists have been shown to inhibit inflammatory gene expression, alter Abeta homeostasis and exhibit neuroprotective effects. Importantly, recent clinical trials of FDA approved PPARgamma agonists have been shown to improve cognition and memory in AD patients. Thus, PPARgamma agonists represent a new and potentially efficacious treatment of AD.