Kaundal Ravinder K, Sharma Shyam S
Department of Pharmacology and Toxicology of the National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India.
Drug News Perspect. 2010 May;23(4):241-56. doi: 10.1358/dnp.2010.23.4.1437710.
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.
过氧化物酶体增殖物激活受体γ（PPARγ）已被视为治疗代谢紊乱的一个有吸引力的治疗靶点。最近，PPARγ激动剂被证明能有效减轻中枢神经系统的氧化应激、炎症和细胞凋亡。有多项临床前和临床研究表明，PPARγ激动剂在治疗脑缺血、帕金森病、阿尔茨海默病、多发性硬化症和肌萎缩侧索硬化症方面具有神经保护潜力。在这些疾病中，PPARγ激动剂除了抑制氧化应激、炎症和细胞凋亡外，还具有调节各种信号分子/信号通路的潜力，包括基质金属蛋白酶-9、丝裂原活化蛋白激酶、信号转导和转录激活因子、线粒体解偶联蛋白2、线粒体内膜电子传递体表达、淀粉样前体蛋白降解、β-位点淀粉样前体蛋白裂解酶1和Wnt信号通路。本文讨论了支持PPARγ激动剂在中枢神经系统疾病中神经保护作用的证据和机制。
