运动提高沉默信息调节因子2相关酶1改善阿尔兹海默症

阿尔兹海默症(Alzheimer's disease, AD)是一种神经退行性疾病,β-淀粉样蛋白(β-amyloid, Aβ)沉积和Tau蛋白过度磷酸化是其主要病理特征。沉默信息调节因子2相关酶1 (silent mating-type information regulation 2 homolog 1, SIRT1)具有去乙酰化作用,能够使多种类型组蛋白及非组蛋白脱乙酰化,在AD发病过程中占据重要地位。近年研究发现,运动能够激活SIRT1减缓AD进程,其机制可能是:抑制β-分泌酶活性、提高α-分泌酶活性,减少Aβ生成;减少过度磷酸化Tau蛋白集聚;与过氧化体增殖物激活型受体γ辅激活因子-1α(peroxisome proliferator-activated receptor γ coactivator-1α,PGC-1α)相互作用以促进线粒体生物发生;上调同源性磷酸酶张力蛋白诱导激酶1(phosphatase and tensin homolog induced putative kinase1,PINK1)/Parkin信号通路改善线粒体自噬;去乙酰化核转录因子-κB(nuclear factor kappa B, NF-κB)以抑制神经炎症;提高海马中脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)、神经胶质源性营养因子(glial cellline-derived neurotrophic factor,GDNF)等营养因子的蛋白质水平,以及抑制ApoE4基因进而增强神经元突触可塑性。本文总结了运动通过调控SIRT1改善AD的作用和机制,为预防及治疗AD提供新的思路。

Exercise Enhances SIRT1 Expression and Improves Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disease, β-amyloid (Aβ) deposition and Tau protein hyperphosphorylation are the main pathological features. Silent mating-type information regulation 2 homolog 1 (SIRT1) can deacetylate various types of histones and non-histones, and play an important role in the pathogenesis of AD. Recent studies found that exercise can activate SIRT1 to delay the progression of AD. The mechanisms may be as follows: inhibit the activity of β-secretase and increase the activity of α-secretase to reduce the production of Aβ; reduce the accumulation of hyperphosphorylated Tau protein; interact with PGC-1α to promote mitochondrial biogenesis; up-regulate PINK1/Parkin signaling pathway to improve mitochondrial autophagy; and deacetylate NF-κB to inhibit neuroinflammation. In addition, the protein levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in hippocampus are increased, and ApoE4 gene is inhibited to enhance synaptic plasticity. This article summarizes the role and mechanisms of exercise in improving AD by regulating SIRT1, and provides new ideas for the prevention and treatment of AD.