Yan Xu, Wang Biyao, Hu Yue, Wang Sijian, Zhang Xinwen
The VIP Department, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China.
Center of Implant Dentistry, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China.
Front Cell Neurosci. 2020 Jun 23;14:138. doi: 10.3389/fncel.2020.00138. eCollection 2020.
Neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis, are characterized by a progressive loss of selective neuron subtypes in the central nervous system (CNS). Although various factors account for the initiation and development of these diseases, accumulating evidence shows that impaired mitochondrial function is a prominent and common mechanism. Mitochondria play a critical role in neurons and are involved in energy production, cellular metabolism regulation, intracellular calcium homeostasis, immune responses, and cell fate. Thus, cells in the CNS heavily rely on mitochondrial integrity. Many aspects of mitochondrial dysfunction are manifested in neurodegenerative diseases, including aberrant mitochondrial quality control (mitoQC), mitochondrial-driven inflammation, and bioenergetic defects. Herein, we briefly summarize the molecular basis of mitoQC, including mitochondrial proteostasis, biogenesis, dynamics, and organelle degradation. We also focus on the research, to date, regarding aberrant mitoQC and mitochondrial-driven inflammation in several common neurodegenerative diseases. In addition, we outline novel therapeutic strategies that target aberrant mitoQC in neurodegenerative diseases.
神经退行性疾病，包括阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症，其特征是中枢神经系统（CNS）中选择性神经元亚型逐渐丧失。尽管多种因素导致了这些疾病的发生和发展，但越来越多的证据表明，线粒体功能受损是一个突出且常见的机制。线粒体在神经元中起着关键作用，参与能量产生、细胞代谢调节、细胞内钙稳态、免疫反应和细胞命运决定。因此，中枢神经系统中的细胞严重依赖线粒体的完整性。线粒体功能障碍的许多方面都表现在神经退行性疾病中，包括异常的线粒体质量控制（mitoQC）、线粒体驱动的炎症和生物能量缺陷。在此，我们简要总结mitoQC的分子基础，包括线粒体蛋白质稳态、生物发生、动力学和细胞器降解。我们还关注到目前为止关于几种常见神经退行性疾病中异常mitoQC和线粒体驱动炎症的研究。此外，我们概述了针对神经退行性疾病中异常mitoQC的新型治疗策略。
