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线粒体自噬的分子机制及其在神经退行性疾病中的作用。

Molecular mechanisms of mitophagy and its roles in neurodegenerative diseases.

机构信息

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

Department of Neurology, Beijing Tsinghua Changgung Hospital, Beijing 102218, China.

出版信息

Pharmacol Res. 2021 Jan;163:105240. doi: 10.1016/j.phrs.2020.105240. Epub 2020 Oct 11.

Abstract

Neurodegenerative diseases are the most common diseases of the nervous system in elderly people, which are currently incurable and cause great burden to families and societies. Mitochondria are the energy factory of the cell and have extremely important effects on neuronal function. The elimination of dysfunctional mitochondria is essential for the mitochondrial metabolic homeostasis, energy supply, and neuronal survival. Recent studies suggest that the impaired mitophagy may lead to the accumulation of damaged mitochondria and therefore contribute to the progression of neurodegenerative diseases. This review mainly focuses on mitophagy, mitochondrial dynamics, and their abnormal changes in neurodegenerative diseases, as well as the therapeutic strategies targeting mitophagy that have shown promise in recent preclinical and clinical studies.

摘要

神经退行性疾病是老年人神经系统最常见的疾病,目前尚无治愈方法,给家庭和社会带来了巨大负担。线粒体是细胞的能量工厂,对神经元功能有极其重要的影响。消除功能失调的线粒体对于线粒体代谢平衡、能量供应和神经元存活至关重要。最近的研究表明,受损的线粒体自噬可能导致受损线粒体的积累,从而促进神经退行性疾病的进展。本综述主要关注线粒体自噬、线粒体动力学及其在神经退行性疾病中的异常变化,以及最近临床前和临床研究中显示出前景的针对线粒体自噬的治疗策略。

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