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多发性硬化症中的自噬:同一硬币的两面

Autophagy in Multiple Sclerosis: Two Sides of the Same Coin.

作者信息

Misrielal Chairi, Mauthe Mario, Reggiori Fulvio, Eggen Bart J L

机构信息

Molecular Neurobiology, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Molecular Cell Biology, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

出版信息

Front Cell Neurosci. 2020 Nov 20;14:603710. doi: 10.3389/fncel.2020.603710. eCollection 2020.

Abstract

Multiple sclerosis (MS) is a complex auto-immune disorder of the central nervous system (CNS) that involves a range of CNS and immune cells. MS is characterized by chronic neuroinflammation, demyelination, and neuronal loss, but the molecular causes of this disease remain poorly understood. One cellular process that could provide insight into MS pathophysiology and also be a possible therapeutic avenue, is autophagy. Autophagy is an intracellular degradative pathway essential to maintain cellular homeostasis, particularly in neurons as defects in autophagy lead to neurodegeneration. One of the functions of autophagy is to maintain cellular homeostasis by eliminating defective or superfluous proteins, complexes, and organelles, preventing the accumulation of potentially cytotoxic damage. Importantly, there is also an intimate and intricate interplay between autophagy and multiple aspects of both innate and adaptive immunity. Thus, autophagy is implicated in two of the main hallmarks of MS, neurodegeneration, and inflammation, making it especially important to understand how this pathway contributes to MS manifestation and progression. This review summarizes the current knowledge about autophagy in MS, in particular how it contributes to our understanding of MS pathology and its potential as a novel therapeutic target.

摘要

多发性硬化症(MS)是一种中枢神经系统(CNS)的复杂自身免疫性疾病,涉及一系列中枢神经系统和免疫细胞。MS的特征是慢性神经炎症、脱髓鞘和神经元丧失,但这种疾病的分子病因仍知之甚少。自噬是一种细胞内降解途径,对于维持细胞内稳态至关重要,尤其是在神经元中,因为自噬缺陷会导致神经退行性变。自噬的功能之一是通过清除有缺陷或多余的蛋白质、复合物和细胞器来维持细胞内稳态,防止潜在的细胞毒性损伤积累。重要的是,自噬与先天免疫和适应性免疫的多个方面之间也存在密切而复杂的相互作用。因此,自噬与MS的两个主要特征——神经退行性变和炎症有关,这使得了解该途径如何促进MS的表现和进展尤为重要。本综述总结了目前关于MS中自噬的知识,特别是它如何有助于我们理解MS病理学及其作为新型治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea96/7714924/312eb7f0faa9/fncel-14-603710-g001.jpg

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