神经退行性疾病中线粒体DNA拷贝数的变化及其调控

doi:10.13865/j.cnki.cjbmb.2020.10.1270

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摘要神经退行性疾病是机体神经元的结构或功能逐渐丧失所引发的一类疾病，它严重危害人类健康。线粒体功能障碍是神经退行性疾病的早期病理现象，同时也是该类疾病的发病机制之一。线粒体DNA(mitochondrial DNA，mtDNA)拷贝数的维持对线粒体功能的正常行使十分重要，它的异常变化通常与线粒体功能异常密切相关。mtDNA拷贝数的下降可引起线粒体呼吸链缺陷，进而导致线粒体功能障碍。而mtDNA拷贝数的增加通常是线粒体功能受损后的代偿性复制所导致的。近年大量的研究表明，mtDNA拷贝数变化与神经退行性疾病的发生发展密切相关，mtDNA拷贝数可能成为潜在生物标志物，在神经退行性疾病的诊断和预后中发挥作用。本文综述了阿尔兹海默症(Alzheimer’s disease，AD)、帕金森病(Parkinson’s disease，PD)、亨廷顿病(Huntington’s disease，HD)、肌萎缩侧索硬化症(amyotrophic lateral sclerosis，ALS)、多发性硬化症(multiple sclerosis，MS)等几种典型的神经退行性疾病中，病变神经组织、脑脊液和外周血中mtDNA拷贝数变化的规律，以及D环区突变、D环区甲基化、mtDNA复制转录因子、线粒体自噬等因素介导神经退行性疾病中mtDNA变化的调控机制。以期为深入系统揭示神经退行性疾病中mtDNA拷贝数变化的调控机制，以及mtDNA拷贝数在神经退行性疾病的诊断、预后及治疗中的应用提供参考。

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	李俊
	王红娟
	胡清源

关键词 ：神经退行性疾病, 线粒体DNA拷贝数, D环区, 线粒体DNA复制转录因子, 线粒体自噬

Abstract：Neurodegenerative disease are kinds of diseases caused by gradual loss of the structure or function of neurons in the body, which seriously endangers human health. Mitochondrial dysfunction is an early pathological phenomenon of neurodegenerative diseases, and is also one of the pathogenesis of such diseases. The maintenance of mitochondrial DNA (mtDNA) copy number is very important for the normal exercise of mitochondrial function, and its abnormal changes are often closely related to the abnormal mitochondrial function. The decrease of mtDNA copy number can cause mitochondrial respiratory chain defects, and then lead to mitochondrial dysfunction. However, the increase of mtDNA copy number is often caused by compensatory replication after mitochondrial dysfunction. In recent years, more and more studies have shown that the change of mtDNA copy number is closely related to the occurrence and development of neurodegenerative diseases, and mtDNA copy number may become a potential biomarker to play a role in the diagnosis and prognosis of neurodegenerative diseases. In this article, the changes of mtDNA copy number in pathological nerve tissue, cerebrospinal fluid and peripheral blood in several typical neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), and the regulatory mechanism of mtDNA changes in neurodegenerative diseases mediated by D-loop mutation, D-loop methylation, mtDNA replication transcription factor and mitochondrial autophagy were reviewed. This article will provide reference for revealing the regulatory mechanism of mtDNA copy number changes in neurodegenerative diseases, and the application of mtDNA copy number in the diagnosis, prognosis and treatment of neurodegenerative diseases.

Key words： neurodegenerative diseases mitochondrial DNA copy number D-loop mitochondrial DNA replication and transcription factor mitophagy

收稿日期: 2020-05-12 出版日期: 2020-07-17

PACS:	Q71
	R741

通讯作者: 胡清源 E-mail: hqy1965@163.com

引用本文:

李俊，王红娟，胡清源. 神经退行性疾病中线粒体DNA拷贝数的变化及其调控[J]. 中国生物化学与分子生物学报, 2020, 36(12): 1431-1437.
LI Jun, WANG Hong-Juan, HU Qing-Yuan. Changes of Mitochondrial DNA Copy Number and Its Regulation in Neurodegenerative Diseases. Chinese Journal of Biochemistry and Molecular Biol, 2020, 36(12): 1431-1437.

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http://cjbmb.bjmu.edu.cn/CN/ 10.13865/j.cnki.cjbmb.2020.10.1270 或 http://cjbmb.bjmu.edu.cn/CN/Y2020/V36/I12/1431

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