PPARα与阿尔茨海默病的研究进展

PPARα in Alzheimer’s Disease

阿尔茨海默病(Alzheimer’s disease,AD)是一种进行性、破坏认知与记忆功能的持续性神经退行性疾病.它的主要病理特征是以β淀粉样蛋白(β-amyloid protein,Aβ)沉积和Tau蛋白过度磷酸化形成神经原纤维缠结(neurofibrillary tangle,NFT)为主,是一种日益严重的全球健康性问题.过氧化物酶体增殖物激活受体(peroxisome proliferators-activated receptor,PPAR)是在中枢神经系统(CNS)中表达,调节能量代谢、神经传递、氧化还原稳态、线粒体功能等生理过程的一种核受体. PPARα作为其中一个亚型,在AD控制突触可塑性和调节神经元认知功能中有重要作用,说明PPARα是治疗AD的一个很有前途的靶点.这篇综述探讨了Aβ、氧化应激、神经炎症、脂质代谢在AD中的意义,以及PPARα的潜在价值及其在AD中的作用,揭示了未来PPARα作为AD治疗靶点的可能性.

Alzheimer’s disease(AD) is a neurodegenerative disease with progressive and persistent cognition and memory destruction. Its main pathological features are β-amyloid(Aβ) deposition and neurofibril tangles formed by hyperphosphorylated Tau protein, which is becoming a serious global health problem. Peroxisome proliferators-activated receptors(PPARs) is a nuclear receptor that expresses in the central nervous system and regulates energy metabolism, neurotransmission, redox homeostasis, mitochondrial function and other physiological processes. PPARα, as one of the subtypes, plays an important role in the control of synaptic plasticity and neuronal function. In this review, we discussed the possibility of PPARα as a therapeutic target for AD treatment. PPARα can reduce the production of soluble amyloid precursor protein(s APP) and Aβ by regulating β secretase-1(BACE-1) and reduce the accumulation of reactive oxygen species(ROS) by regulating the function of mitochondria, thereby decreasing oxidative stress damage. PPARα can down-regulate inflammatory factors and lessen neuroinflammation. It can also decrease blood lipids, alleviate insulin resistance,and regulate lipids metabolism. PPARα, as a promising target for the treatment of AD, is of great significance to new treatment strategies for AD.