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多发性硬化症中的线粒体:发病机制的分子机制

Mitochondria in Multiple Sclerosis: Molecular Mechanisms of Pathogenesis.

作者信息

Patergnani S, Fossati V, Bonora M, Giorgi C, Marchi S, Missiroli S, Rusielewicz T, Wieckowski M R, Pinton P

机构信息

Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.

The New York Stem Cell Foundation Research Institute, New York, NY, United States.

出版信息

Int Rev Cell Mol Biol. 2017;328:49-103. doi: 10.1016/bs.ircmb.2016.08.003. Epub 2016 Sep 28.

Abstract

Mitochondria, the organelles that function as the powerhouse of the cell, have been increasingly linked to the pathogenesis of many neurological disorders, including multiple sclerosis (MS). MS is a chronic inflammatory demyelinating disease of the central nervous system (CNS) and a leading cause of neurological disability in young adults in the western world. Its etiology remains unknown, and while the inflammatory component of MS has been heavily investigated and targeted for therapeutic intervention, the failure of remyelination and the process of axonal degeneration are still poorly understood. Recent studies suggest a role of mitochondrial dysfunction in the neurodegenerative aspects of MS. This review is focused on mitochondrial functions under physiological conditions and the consequences of mitochondrial alterations in various CNS disorders. Moreover, we summarize recent findings linking mitochondrial dysfunction to MS and discuss novel therapeutic strategies targeting mitochondria-related pathways as well as emerging experimental approaches for modeling mitochondrial disease.

摘要

线粒体作为细胞的动力源细胞器,越来越多地与包括多发性硬化症(MS)在内的许多神经系统疾病的发病机制联系在一起。MS是一种中枢神经系统(CNS)的慢性炎症性脱髓鞘疾病,是西方世界年轻人神经残疾的主要原因。其病因尚不清楚,虽然MS的炎症成分已得到大量研究并作为治疗干预的靶点,但髓鞘再生失败和轴突变性过程仍知之甚少。最近的研究表明线粒体功能障碍在MS的神经退行性方面发挥作用。本综述重点关注生理条件下的线粒体功能以及各种中枢神经系统疾病中线粒体改变的后果。此外,我们总结了将线粒体功能障碍与MS联系起来的最新发现,并讨论了针对线粒体相关途径的新型治疗策略以及线粒体疾病建模的新兴实验方法。

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