自噬在神经退行性疾病中的作用研究进展

The molecular mechanism of autophagy and its research progress in neurodegenerative diseases

自噬是细胞内溶酶体介导的降解错误折叠蛋白及衰老损伤细胞器的生命过程,广泛存在于真核细胞中。自噬在维持细胞稳态和物质能量再循环中具有重要作用。近年来,在许多组织和器官中发现了自噬的特殊功能。值得注意的是,自噬在神经退行性疾病中的作用越来越被人们所重视。神经元自噬功能紊乱和异常蛋白质聚集折叠是神经退行性疾病的主要病理改变。研究表明,自噬调节与阿尔茨海默病淀粉样蛋白、帕金森病路易小体和亨廷顿病中亨廷顿蛋白等的清除具有密切联系。此外,天然药物包括白藜芦醇、海藻糖、姜黄素等已被证明在神经退行性疾病中通过调控自噬发挥着积极作用。因此,进一步了解自噬的机制对神经退行性疾病的治疗至关重要。现对自噬的分子机制及其在神经退行性疾病中的进展作一综述,旨在为神经退行性疾病的临床治疗提供参考。

Autophagy is a life process mediated by the intracellular lysosomes that can degrade intracellular misfolded proteins and aging damaged organelles,and is widely found in eukaryotic cells.Autophagy plays a crucial role in maintaining cell homeostasis and the recycling of material and energy.Some specific functions of autophagy have been identified in many tissues and organs resent years.Notably,the role of autophagy in neurodegenerative diseases has been paid more and more attention.Neurodegenerative diseases are a pathological process characterized by neuronal autophagy dysfunction and abnormal protein aggregation and folding.Studies have showed that autophagy can reduce amyloid accumulation in Alzheimer disease(AD),promote the clearance of Lewy bodies in Parkinson's disease(PD)and reduce the level of huntington protein in Huntington's disease(HD).In addition,natural drugs including resveratrol,trehalose and curcumin have been shown to play an active role in neurodegenerative diseases by regulation of autophagy.Therefore,understanding the molecular mechanisms of autophagy is critical for the treatment of neurodegenerative disease.This review focused on the molecular mechanism of autophagy and its research progress in neurodegenerative diseases,aiming to provide reference for the clinical treatment of neurodegenerative disease.