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治疗神经退行性疾病的靶向线粒体方法的新希望。

Emerging Promise of Therapeutic Approaches Targeting Mitochondria in Neurodegenerative Disorders.

机构信息

Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh.

Department of Physiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

Curr Neuropharmacol. 2023;21(5):1081-1099. doi: 10.2174/1570159X21666230316150559.

Abstract

Mitochondria are critical for homeostasis and metabolism in all cellular eukaryotes. Brain mitochondria are the primary source of fuel that supports many brain functions, including intracellular energy supply, cellular calcium regulation, regulation of limited cellular oxidative capacity, and control of cell death. Much evidence suggests that mitochondria play a central role in neurodegenerative disorders (NDDs) such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Ongoing studies of NDDs have revealed that mitochondrial pathology is mainly found in inherited or irregular NDDs and is thought to be associated with the pathophysiological cycle of these disorders. Typical mitochondrial disturbances in NDDs include increased free radical production, decreased ATP synthesis, alterations in mitochondrial permeability, and mitochondrial DNA damage. The main objective of this review is to highlight the basic mitochondrial problems that occur in NDDs and discuss the use mitochondrial drugs, especially mitochondrial antioxidants, mitochondrial permeability transition blockade, and mitochondrial gene therapy, for the treatment and control of NDDs.

摘要

线粒体对于所有真核细胞的内环境稳定和代谢都至关重要。脑线粒体是支持许多大脑功能的主要燃料来源,包括细胞内能量供应、细胞内钙调节、有限的细胞氧化能力调节和细胞死亡控制。大量证据表明,线粒体在神经退行性疾病(NDDs)中发挥着核心作用,如帕金森病、阿尔茨海默病、亨廷顿病和肌萎缩侧索硬化症。对 NDDs 的持续研究表明,线粒体病理学主要存在于遗传性或不规则 NDDs 中,并且与这些疾病的病理生理周期有关。NDDs 中典型的线粒体紊乱包括自由基产生增加、ATP 合成减少、线粒体通透性改变和线粒体 DNA 损伤。本综述的主要目的是强调发生在 NDDs 中的基本线粒体问题,并讨论使用线粒体药物,特别是线粒体抗氧化剂、线粒体通透性转换阻断剂和线粒体基因治疗,来治疗和控制 NDDs。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed7f/10286587/ee2be2bb3586/CN-21-1081_F1.jpg

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