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靶向线粒体在神经退行性疾病调控中的作用:全面综述。

Targeting mitochondria in the regulation of neurodegenerative diseases: A comprehensive review.

机构信息

Department of Zoology, University of Delhi, Delhi, India.

Stem Cell Facility, All India Institute of Medical Sciences, Delhi, India.

出版信息

J Neurosci Res. 2022 Oct;100(10):1845-1861. doi: 10.1002/jnr.25110. Epub 2022 Jul 20.

Abstract

Mitochondria are one of the essential cellular organelles. Apart from being considered as the powerhouse of the cell, mitochondria have been widely known to regulate redox reaction, inflammation, cell survival, cell death, metabolism, etc., and are implicated in the progression of numerous disease conditions including neurodegenerative diseases. Since brain is an energy-demanding organ, mitochondria and their functions are important for maintaining normal brain homeostasis. Alterations in mitochondrial gene expression, mutations, and epigenetic modification contribute to inflammation and neurodegeneration. Dysregulation of reactive oxygen species production by mitochondria and aggregation of proteins in neurons leads to alteration in mitochondria functions which further causes neuronal death and progression of neurodegeneration. Pharmacological studies have prioritized mitochondria as a possible drug target in the regulation of neurodegenerative diseases. Therefore, the present review article has been intended to provide a comprehensive understanding of mitochondrial role in the development and progression of neurodegenerative diseases mainly Alzheimer's, Parkinson's, multiple sclerosis, and amyotrophic lateral sclerosis followed by possible intervention and future treatment strategies to combat mitochondrial-mediated neurodegeneration.

摘要

线粒体是一种重要的细胞细胞器。除了被认为是细胞的“动力工厂”外,线粒体还广泛参与调节氧化还原反应、炎症、细胞存活、细胞死亡、代谢等过程,并与包括神经退行性疾病在内的许多疾病的发展有关。由于大脑是一个高能耗的器官,线粒体及其功能对于维持正常的大脑内稳态非常重要。线粒体基因表达的改变、突变和表观遗传修饰会导致炎症和神经退行性变。线粒体产生的活性氧物质的失调和神经元中蛋白质的聚集导致线粒体功能的改变,进一步导致神经元死亡和神经退行性变的发展。药理学研究已经将线粒体作为调节神经退行性疾病的一个可能的药物靶点。因此,本综述文章旨在提供对线粒体在阿尔茨海默病、帕金森病、多发性硬化症和肌萎缩侧索硬化症等神经退行性疾病的发生和发展中的作用的全面理解,随后探讨了针对线粒体介导的神经退行性变的可能干预和未来治疗策略。

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