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线粒体分裂抑制剂作为治疗氧化应激和线粒体功能障碍相关疾病的一种策略。

Inhibitors of mitochondrial fission as a therapeutic strategy for diseases with oxidative stress and mitochondrial dysfunction.

作者信息

Reddy P Hemachandra

机构信息

Neurogenetics Laboratory, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR, USA.

出版信息

J Alzheimers Dis. 2014;40(2):245-56. doi: 10.3233/JAD-132060.

Abstract

Mitochondria are essential cytoplasmic organelles, critical for cell survival and death. Recent mitochondrial research revealed that mitochondrial dynamics-the balance of fission and fusion in normal mitochondrial dynamics--is an important cellular mechanism in eukaryotic cell and is involved in the maintenance of mitochondrial morphology, structure, number, distribution, and function. Research into mitochondria and cell function has revealed that mitochondrial dynamics is impaired in a large number of aging and neurodegenerative diseases, and in several inherited mitochondrial diseases, and that this impairment involves excessive mitochondrial fission, resulting in mitochondrial structural changes and dysfunction, and cell damage. Attempts have been made to develop molecules to reduce mitochondrial fission while maintaining normal mitochondrial fusion and function in those diseases that involve excessive mitochondrial fission. This review article discusses mechanisms of mitochondrial fission in normal and diseased states of mammalian cells and discusses research aimed at developing therapies, such as Mdivi, Dynasore and P110, to prevent or to inhibit excessive mitochondrial fission.

摘要

线粒体是重要的细胞质细胞器,对细胞存活和死亡至关重要。近期的线粒体研究表明,线粒体动力学——正常线粒体动力学中裂变与融合的平衡——是真核细胞中的一种重要细胞机制,参与线粒体形态、结构、数量、分布和功能的维持。对线粒体与细胞功能的研究表明,在大量衰老和神经退行性疾病以及一些遗传性线粒体疾病中,线粒体动力学受损,且这种损伤涉及线粒体过度裂变,导致线粒体结构改变和功能障碍以及细胞损伤。人们已尝试开发分子,以在那些涉及线粒体过度裂变的疾病中减少线粒体裂变,同时维持正常的线粒体融合和功能。这篇综述文章讨论了哺乳动物细胞正常和疾病状态下的线粒体裂变机制,并探讨了旨在开发如Mdivi、Dynasore和P110等疗法以预防或抑制线粒体过度裂变的研究。

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