The Role of Mitochondria in Neurodegenerative Diseases: the Lesson from Alzheimer's Disease and Parkinson's Disease.
The Role of Mitochondria in Neurodegenerative Diseases: the Lesson from Alzheimer's Disease and Parkinson's Disease.
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线粒体在神经退行性疾病中的作用：来自阿尔茨海默病和帕金森病的启示
DOI：
10.1007/s12035-020-01926-1
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发表时间：
2020-07
影响因子：
5.1
通讯作者：
Masliah, Eliezer
中科院分区：
文献类型：
--
作者：
Compagnoni, Giacomo Monzio;Di Fonzo, Alessio;Corti, Stefania;Comi, Giacomo P.;Bresolin, Nereo;Masliah, Eliezer
虽然神经退行性疾病的发病机制仍不清楚，但已提出了各种机制，并且有几项证据支持线粒体功能障碍的重要作用。本综述提供了一个全面的和最新的概述线粒体的作用，在两个最常见的神经退行性疾病：阿尔茨海默病（AD）和帕金森病（PD）。线粒体参与AD得到了临床特征（如葡萄糖和氧脑代谢降低）以及许多显微镜和分子学发现（包括线粒体形态改变、呼吸链功能受损和线粒体DNA改变）的支持。此外，淀粉样蛋白病理学和线粒体功能障碍似乎是双向相关的。线粒体在PD中具有更显著的作用。几个提示表明，呼吸链活动，特别是复合物I，在疾病中受损。线粒体DNA的改变，包括缺失、点突变、消耗和改变的维持，已经被描述。与线粒体功能直接相关的基因突变（如Parkin和PINK 1）是导致罕见遗传形式的疾病的原因。已经观察到α-突触核蛋白积累和线粒体功能障碍之间的密切联系。最后，线粒体也参与非典型帕金森症，特别是多系统萎缩。现有的知识仍然不足以清楚地说明线粒体功能障碍是否在这些疾病的最初阶段起主要作用，还是继发于其他现象。然而，所提供的数据强烈支持这一假设，即无论神经变性的最初原因是什么，线粒体损伤在维持和促进神经变性过程中具有关键作用。
Although the pathogenesis of neurodegenerative diseases is still widely unclear, various mechanisms have been proposed and several pieces of evidence are supportive for an important role of mitochondrial dysfunction. The present review provides a comprehensive and up-to-date overview about the role of mitochondria in the two most common neurodegenerative disorders: Alzheimer’s disease (AD) and Parkinson’s disease (PD). Mitochondrial involvement in AD is supported by clinical features like reduced glucose and oxygen brain metabolism and by numerous microscopic and molecular findings, including altered mitochondrial morphology, impaired respiratory chain function, and altered mitochondrial DNA. Furthermore, amyloid pathology and mitochondrial dysfunction seem to be bi-directionally correlated. Mitochondria have an even more remarkable role in PD. Several hints show that respiratory chain activity, in particular complex I, is impaired in the disease. Mitochondrial DNA alterations, involving deletions, point mutations, depletion, and altered maintenance, have been described. Mutations in genes directly implicated in mitochondrial functioning (like Parkin and PINK1) are responsible for rare genetic forms of the disease. A close connection between alpha-synuclein accumulation and mitochondrial dysfunction has been observed. Finally, mitochondria are involved also in atypical parkinsonisms, in particular multiple system atrophy. The available knowledge is still not sufficient to clearly state whether mitochondrial dysfunction plays a primary role in the very initial stages of these diseases or is secondary to other phenomena. However, the presented data strongly support the hypothesis that whatever the initial cause of neurodegeneration is, mitochondrial impairment has a critical role in maintaining and fostering the neurodegenerative process.
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作者：
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