摘要
自噬作为细胞内的一种分解代谢途径,可将胞质中异常聚集的蛋白质、受损细胞器及其他细胞成分转运至溶酶体进行降解,以维持蛋白质稳态和细胞代谢平衡。研究表明,阿尔茨海默病(Alzheimer’s disease, AD)脑内β淀粉样蛋白(amyloid-β, Aβ)沉积、Tau蛋白异常磷酸化和突触可塑性失调与细胞自噬紊乱有关。适宜的运动能够调节神经细胞自噬水平和抑制AD动物脑内的多种病变,但具体机制尚不明确。综述近期研究成果发现,运动可能通过以下途径保护大脑和改善AD:(1)运动可以激活AMP依赖的蛋白激酶(AMP-activated protein kinase, AMPK)和抑制哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)信号诱导自噬启动,提高自噬流和自噬溶酶体的降解,从而促进Aβ和磷酸化Tau蛋白的自噬清除。(2)运动增加脑内脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)表达,经由BDNF/酪氨酸激酶受体B(tyrosine kinase receptor B, TrkB)信号,以及磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinases, PI3K)/蛋白质丝氨酸苏氨酸激酶(protein-serine-threonine kinase, AKT)信号途径调节自噬流,从而介导BDNF诱导的突触可塑性。(3)运动可能通过调节神经细胞自噬,维持神经递质稳态和突触传递。
Autophagy is an essential degradation pathway in clearing abnormal protein aggregates from mammalian cells and is responsible for protein homeostasis and neuronal health.Several studies have shown that autophagy deficits occurred in the brain of Alzheimer’s disease(AD).Defects in autophagy affect the metabolism ofβ-amyloid(Aβ),assembling of Tau,and synaptic plasticity,contributing to the progress of AD.Recently,increasing evidence suggests that aerobic exercise could regulate autophagy,and ameliorate the pathological features of AD animals,but the molecular mechanisms are still unknown.In this review,we summarized the latest progress supporting the role of exercise regulated autophagy in the prevention and treatment of Alzheimer’s disease.Firstly,exercise induces autophagy by activating AMPK and inhibiting mTOR signaling.Exercise enhances autophagy flux and autolysosome degradation,which accelerates the removal of Aβand phosphorylated Tau.Secondly,Exercise increases the amount of BDNF in the brain,which suppresses autophagy flux via the BDNF/TrkB signaling and the PI3K/Akt pathway,thereby promoting synaptic plasticity and memory through a BDNF-regulated mechanism.In addition,exercise may also maintain neurotransmitter homeostasis by regulating autophagy.
作者
夏杰
徐波
XIA Jie;XU Bo(Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education,East China Normal University,Shanghai 200241,China;College of Physical Education and Health,East China Normal University,Shanghai 200241,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2020年第7期748-755,共8页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金项目(No.31571225)资助
