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.

中文翻译：

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线粒体在神经退行性疾病中的作用：阿尔茨海默病和帕金森病的教训。

尽管神经退行性疾病的发病机制仍不清楚，但已经提出了各种机制，并且有一些证据支持线粒体功能障碍的重要作用。本综述提供了关于线粒体在两种最常见的神经退行性疾病中的作用的全面和最新的概述：阿尔茨海默病 (AD) 和帕金森病 (PD)。AD 中的线粒体受累得到临床特征的支持，如葡萄糖和氧脑代谢减少以及许多微观和分子发现，包括线粒体形态改变、呼吸链功能受损和线粒体 DNA 改变。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 中的作用更为显着。一些提示表明，呼吸链活动，特别是复合物 I，在疾病中受损。已经描述了线粒体 DNA 改变，包括缺失、点突变、消耗和改变的维持。与线粒体功能直接相关的基因（如 Parkin 和 PINK1）的突变是导致这种疾病的罕见遗传形式的原因。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，线粒体也与非典型帕金森症有关，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，