PPAR gamma; Pharmaceutical Preparations; Animals; Central Nervous System Diseases/drug therapy; Central Nervous System Diseases/metabolism; Humans; PPAR gamma/agonists; PPAR gamma/physiology; Pharmaceutical Preparations/administration & dosage; Pharmaceutical Preparations/metabolism; Neurology (clinical); Cellular and Molecular Neuroscience; ischemic stroke; multiple sclerosis; neurodegenerative disorders; peroxisome proliferator-activated receptor-gamma
Abstract :
[en] The finding that activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) suppresses inflammation in peripheral macrophages and in models of human autoimmune disease instigated the evaluation of this salutary action for the treatment of CNS disorders with an inflammatory component. The fact that NSAIDs delay the onset of and reduce the risk of developing Alzheimer's disease (AD), while also binding to and activating PPARgamma, led to the hypothesis that one dimension of NSAID protection in AD is mediated by PPARgamma. Several lines of evidence from experiments using AD-related transgenic cellular and animal models have supported this hypothesis. The capacity of PPARgamma agonists to elicit anti-inflammatory, anti-amyloidogenic and insulin-sensitizing effects might account for their observed protective effects. Several clinical trials employing PPARgamma agonists have yielded promising results, and further trials are in preparation. Positive outcomes following PPARgamma administration have been obtained in animal models of other neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis, both of which are associated with a considerable degree of neuroinflammation. Finally, activation of PPARgamma has been found to be protective in several models of multiple sclerosis. The verification of these findings in human cells prompted the initiation of clinical studies evaluating PPARgamma activation in patients with multiple sclerosis.
Disciplines :
Neurology
Author, co-author :
HENEKA, Michael ; Department of Neurology, University of Münster, Germany. heneka@uni-muenster.de
Landreth, Gary E; Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, OH, United States
Hüll, Michael; Department of Geriatric Psychiatry, Centre of Geriatrics and Gerontology, University of Freiburg, Freiburg, Germany
External co-authors :
yes
Language :
English
Title :
Drug insight: effects mediated by peroxisome proliferator-activated receptor-gamma in CNS disorders.
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