Abnormalities of Mitochondrial Dynamics in Neurodegenerative Diseases.
Abnormalities of Mitochondrial Dynamics in Neurodegenerative Diseases.
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DOI：
10.3390/antiox6020025
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发表时间：
2017-04-05
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
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作者：
Gao J;Wang L;Liu J;Xie F;Su B;Wang X
神经退行性疾病是一种无法治愈的破坏性神经系统疾病，其特征是中枢神经系统或外周神经系统中神经元的结构和功能逐渐丧失。线粒体是存在于大多数真核细胞中的细胞器，对神经元的生存是必不可少的，并参与了许多神经元功能。长期以来，线粒体功能障碍一直是多种常见神经退行性疾病的共同显著早期病理特征，包括阿尔茨海默病(AD)、帕金森病(PD)、肌萎缩侧索硬化症(ALS)和亨廷顿病(HD)。线粒体是高度动态的细胞器，经过不断的融合、分裂和运输，其过程不仅控制着线粒体的形态和数量，而且还调节着线粒体的功能和位置。线粒体动力学在神经退行性疾病发病机制中的重要性在几个关键的融合和分裂调控因子如DRP1、OPA1和丝裂原蛋白的fi被识别后日益被揭示。在简要讨论了线粒体融合、分裂、分布和运输的分子机制以及线粒体动力学对神经元功能的重要作用之后，我们回顾了在各种主要神经退行性疾病中观察到的线粒体动力学异常的前人和最新研究，并讨论了以线粒体动力学为靶点作为治疗神经退行性疾病的可能的新策略的可能性。
Neurodegenerative diseases are incurable and devastating neurological disorders characterized by the progressive loss of the structure and function of neurons in the central nervous system or peripheral nervous system. Mitochondria, organelles found in most eukaryotic cells, are essential for neuronal survival and are involved in a number of neuronal functions. Mitochondrial dysfunction has long been demonstrated as a common prominent early pathological feature of a variety of common neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Mitochondria are highly dynamic organelles that undergo continuous fusion, fission, and transport, the processes of which not only control mitochondrial morphology and number but also regulate mitochondrial function and location. The importance of mitochondrial dynamics in the pathogenesis of neurodegenerative diseases has been increasingly unraveled after the identification of several key fusion and fission regulators such as Drp1, OPA1, and mitofusins. In this review, after a brief discussion of molecular mechanisms regulating mitochondrial fusion, fission, distribution, and trafficking, as well as the important role of mitochondrial dynamics for neuronal function, we review previous and the most recent studies about mitochondrial dynamic abnormalities observed in various major neurodegenerative diseases and discuss the possibility of targeting mitochondrial dynamics as a likely novel therapeutic strategy for neurodegenerative diseases.