Peroxisome proliferator-activated receptor gamma agonists as neuroprotective agents.
Peroxisome proliferator-activated receptor gamma (PPARgamma) has already been considered as an attractive therapeutic target for the treatment of metabolic disorders. Recently, PPARgamma agonists were shown to effectively attenuate oxidative stress, inflammation and apoptosis in the central nervous system. There are several preclinical and clinical studies indicating neuroprotective potential of PPARgamma agonists in the treatment of cerebral ischemia, Parkinson's disease, Alzheimer's disease, multiple sclerosis and amyotrophic lateral sclerosis. In these disorders, apart from inhibiting oxidative stress, inflammation and apoptosis, PPARgamma agonists have the potential to modulate various signaling molecules/pathways, including matrix metalloproteinase-9, mitogen-activated protein kinases, signal transducer and activator of transcription, mitochondrial uncoupling protein 2, mitoNEET expression, amyloid precursor protein degradation, beta-site amyloid precursor protein cleaving enzyme 1 and Wnt signaling. This article discusses evidence and mechanisms supporting the neuroprotective effects of PPARgamma agonists in central nervous system disorders.
Kaundal
Ravinder K
RK
Department of Pharmacology and Toxicology of the National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India.
Sharma
Shyam S
SS
D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D002545:Brain Ischemia / Q000188:drug therapy; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D009103:Multiple Sclerosis / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D047495:PPAR gamma / Q000819:agonists* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D061965:Matrix Metalloproteinase Inhibitors; D018696:Neuroprotective Agents; D047495:PPAR gamma; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human