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揭示线粒体功能障碍:关于其对神经退行性疾病影响的全面观点。

Unraveling mitochondrial dysfunction: comprehensive perspectives on its impact on neurodegenerative diseases.

作者信息

Mohamed Yusoff Abdul Aziz, Mohd Khair Siti Zulaikha Nashwa

机构信息

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia.

出版信息

Rev Neurosci. 2024 Aug 20;36(1):53-90. doi: 10.1515/revneuro-2024-0080. Print 2025 Jan 29.

Abstract

Neurodegenerative diseases represent a significant challenge to modern medicine, with their complex etiology and progressive nature posing hurdles to effective treatment strategies. Among the various contributing factors, mitochondrial dysfunction has emerged as a pivotal player in the pathogenesis of several neurodegenerative disorders. This review paper provides a comprehensive overview of how mitochondrial impairment contributes to the development of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, driven by bioenergetic defects, biogenesis impairment, alterations in mitochondrial dynamics (such as fusion or fission), disruptions in calcium buffering, lipid metabolism dysregulation and mitophagy dysfunction. It also covers current therapeutic interventions targeting mitochondrial dysfunction in these diseases.

摘要

神经退行性疾病是现代医学面临的重大挑战,其病因复杂且具有进行性,给有效的治疗策略带来了障碍。在各种促成因素中,线粒体功能障碍已成为几种神经退行性疾病发病机制中的关键因素。本文综述全面概述了线粒体损伤如何导致神经退行性疾病的发展,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,这些是由生物能量缺陷、生物合成损伤、线粒体动力学改变(如融合或裂变)、钙缓冲破坏、脂质代谢失调和线粒体自噬功能障碍所驱动的。它还涵盖了目前针对这些疾病中线粒体功能障碍的治疗干预措施。

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