Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Pharmacol Res. 2021 Mar;165:105433. doi: 10.1016/j.phrs.2021.105433. Epub 2021 Jan 14.
Neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis) commonly characterized by the gradual loss of neurons have a seriously bad impact on motor and cognitive abilities of affected humans and bring great inconvenience to their lives. Mitochondrial dysfunction has been considered the key and common factor for the pathologies of neurodegenerative diseases for that neurons are extremely energy-intensive due to their unique properties in structures and functions. Thus, mitophagy, as a central role of mitochondrial quality control and currently believed to be the most effective pathway to clear dysfunctional or unwanted mitochondria, is rather crucial in the preservation of neuronal health. In addition, mitophagy establishes an intimated link with several other pathways of mitochondrial quality control (e.g., mitochondrial biogenesis and mitochondrial dynamics), and they work together to preserve mitochondrial health. Therefore, in this review, we summarized the recent process on the mechanisms of mitophagy pathways in mammals, it's linking to mitochondrial quality control, its role in several major neurodegenerative diseases, and possible therapeutic interventions focusing on mitophagy pathways. And we expect that it can provide us with more understanding of the mitophagy pathways and more promising approaches for the treatment of neurodegenerative diseases.
神经退行性疾病（如阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症）的特征通常是神经元逐渐丧失，严重影响受影响人类的运动和认知能力，并给他们的生活带来极大不便。由于神经元在结构和功能上具有独特的性质，因此线粒体功能障碍被认为是神经退行性疾病病理学的关键和共同因素。因此，自噬作为线粒体质量控制的核心作用，目前被认为是清除功能失调或不需要的线粒体的最有效途径，对于维持神经元健康至关重要。此外，自噬与线粒体质量控制的其他几个途径（例如线粒体生物发生和线粒体动力学）建立了密切的联系，它们共同作用以维持线粒体健康。因此，在这篇综述中，我们总结了哺乳动物中自噬途径的机制、与线粒体质量控制的联系、在几种主要神经退行性疾病中的作用以及针对自噬途径的可能治疗干预措施的最新进展。我们希望这能为我们提供更多关于自噬途径的理解，并为神经退行性疾病的治疗提供更有前途的方法。
