线粒体自噬在神经退行性疾病中调控的研究进展

Advance in the Regulation of Mitophagy in Neurodegenerative Diseases

神经退行性疾病是一种以神经元发生进行性变性和坏死为基础的中枢神经系性疾病,其普遍特征是错误折叠蛋白质的积累和线粒体损伤。线粒体作为细胞能量产出的中心,是神经元的主要能量来源,对维持神经元的结构和功能至关重要。受损的线粒体导致细胞中的三磷酸腺苷(ATP)供给不足和氧化应激损伤,甚至引起细胞死亡。线粒体自噬是细胞通过自噬-溶酶体途径选择性地清除衰老或受损线粒体的过程,是线粒体质量控制机制的重要组成部分,在维持细胞稳态方面发挥重要的作用。诸多研究表明,线粒体自噬与神经退行性疾病的发生和发展密不可分,激活线粒体自噬或改善线粒体自噬异常能在一定程度上缓解错误折叠蛋白积聚导致的神经损伤。笔者就线粒体自噬的发生机制、线粒体自噬的调控及其在神经退行性疾病发生发展中的作用进行综述,以期为神经退行性疾病的研究和治疗提供参考。

Neurodegenerative disease is a central nervous system disease based on the progressive degeneration and necrosis of neurons,which is commonly characterized by the accumulation of misfolded proteins and mitochondrial damage.As the center of cellular energy production,mitochondria are the main energy source of neurons and are essential for maintaining the structure and function of neurons.Damaged mitochondria lead to inadequate ATP supply and oxidative stress damage,and even resulte in cellular death.Mitophagy is a process by which cells selectively remove senescent or damaged mitochondria through the autophagy-lysosome pathway.It is an important part of mitochondrial quality control mechanism and plays an important role in maintaining cellular homeostasis.Many studies have suggested that mitophagy is closely related to the occurrence and development of neurodegenerative diseases.Activation of mitophagy or improvement of mitophagy abnormalities can alleviate neuronal damage caused by misfolded protein accumulation.In this paper,the author reviewed the mechanism of mitophagy,its regulation and its role in the occurrence and development of neurodegenerative diseases,which was in order to provide reference for the research and treatment of neurodegenerative diseases.