线粒体 DNA 维持与改变在神经退行性疾病发病机制中的作用。
mtDNA Maintenance and Alterations in the Pathogenesis of Neurodegenerative Diseases.
机构信息
Center of Implant Dentistry, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China.
The VIP Department, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China.
出版信息
Curr Neuropharmacol. 2023;21(3):578-598. doi: 10.2174/1570159X20666220810114644.
Considerable evidence indicates that the semiautonomous organelles mitochondria play key roles in the progression of many neurodegenerative disorders. Mitochondrial DNA (mtDNA) encodes components of the OXPHOS complex but mutated mtDNA accumulates in cells with aging, which mirrors the increased prevalence of neurodegenerative diseases. This accumulation stems not only from the misreplication of mtDNA and the highly oxidative environment but also from defective mitophagy after fission. In this review, we focus on several pivotal mitochondrial proteins related to mtDNA maintenance (such as ATAD3A and TFAM), mtDNA alterations including mtDNA mutations, mtDNA elimination, and mtDNA release-activated inflammation to understand the crucial role played by mtDNA in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Our work outlines novel therapeutic strategies for targeting mtDNA.
大量证据表明，半自主细胞器线粒体在许多神经退行性疾病的进展中发挥着关键作用。线粒体 DNA（mtDNA）编码 OXPHOS 复合物的组成部分，但随着衰老，mtDNA 在细胞中积累，这与神经退行性疾病的发病率增加相吻合。这种积累不仅源于 mtDNA 的错误复制和高度氧化的环境，还源于分裂后有缺陷的线粒体自噬。在这篇综述中，我们重点介绍了几种与 mtDNA 维持相关的关键线粒体蛋白（如 ATAD3A 和 TFAM）、mtDNA 改变，包括 mtDNA 突变、mtDNA 消除和 mtDNA 释放激活炎症，以了解 mtDNA 在阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和亨廷顿病等神经退行性疾病发病机制中的关键作用。我们的工作概述了针对 mtDNA 的新的治疗策略。
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