Anti-inflammatory actions of peroxisome proliferator-activated receptor gamma agonists in Alzheimer's disease.
The role of inflammatory processes in the brains of Alzheimer's Disease (AD) patients has recently attracted considerable interest. Indeed, the only demonstrated effective therapy for AD patients is long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs). The mechanistic basis of the efficacy of NSAIDs in AD remains unclear. However, the recent recognition that NSAIDs can bind to and activate the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma), has offered an explanation for the action of these drugs in AD. PPARgamma activation leads to the inhibition of microglial activation and the expression of a broad range of proinflammatory molecules. The newly appreciated anti-inflammatory actions of PPARgamma agonists may allow novel therapies for AD and other CNS indications with an inflammatory component.
Landreth
G E
GE
Department of Neurosciences, Alzheimer Research Laboratory, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA. gel2@po.cwru.edu
Heneka
M T
MT
D000544:Alzheimer Disease / Q000473:pathology* / Q000517:prevention & control*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000096:biosynthesis / Q000502:physiology; D014157:Transcription Factors / Q000819:agonists* / Q000096:biosynthesis / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors