线粒体功能障碍在神经退行性疾病的发生和发展中的作用。

Mitochondrial dysfunction in the development and progression of neurodegenerative diseases.

机构信息

University of Pennsylvania, Philadelphia, PA, USA.

University of California, Los Angeles, CA, USA.

出版信息

Arch Biochem Biophys. 2021 May 15;702:108698. doi: 10.1016/j.abb.2020.108698. Epub 2020 Nov 28.

DOI:10.1016/j.abb.2020.108698

PMID:33259796

Abstract

In addition to ATP synthesis, mitochondria are highly dynamic organelles that modulate apoptosis, ferroptosis, and inflammasome activation. Through executing these varied functions, the mitochondria play critical roles in the development and progression of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Friedreich ataxia, among others. Impaired mitochondrial biogenesis and abnormal mitochondrial dynamics contribute to mitochondrial dysfunction in these diseases. Additionally, dysfunctional mitochondria play critical roles in signaling for both inflammasome activation and ferroptosis. Therapeutics are being developed to circumvent inflammasome activation and ferroptosis in dysfunctional mitochondria. Targeting these aspects of mitochondrial dysfunction may present viable therapeutic strategies for combatting the neurodegenerative diseases. This review aims to summarize the role of the mitochondria in the development and progression of neurodegenerative diseases and to present current therapeutic approaches that target mitochondrial dysfunction in these diseases.

摘要

除了 ATP 合成，线粒体还是高度动态的细胞器，可调节细胞凋亡、铁死亡和炎症小体激活。通过执行这些不同的功能，线粒体在神经退行性疾病（包括阿尔茨海默病、帕金森病、亨廷顿病和弗里德里希共济失调等）的发生和发展中发挥着关键作用。线粒体生物发生受损和线粒体动力学异常导致这些疾病中线粒体功能障碍。此外，功能失调的线粒体在炎症小体激活和铁死亡的信号传递中发挥关键作用。目前正在开发治疗方法以避免功能失调的线粒体中的炎症小体激活和铁死亡。针对线粒体功能障碍的这些方面可能为对抗神经退行性疾病提供可行的治疗策略。本综述旨在总结线粒体在神经退行性疾病的发生和发展中的作用，并介绍目前针对这些疾病中线粒体功能障碍的治疗方法。