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高尔基体:自噬相关神经疾病的潜在治疗靶点。

Golgi Apparatus: A Potential Therapeutic Target for Autophagy-Associated Neurological Diseases.

作者信息

Deng Shuwen, Liu Jia, Wu Xiaomei, Lu Wei

机构信息

Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.

出版信息

Front Cell Dev Biol. 2020 Sep 9;8:564975. doi: 10.3389/fcell.2020.564975. eCollection 2020.

Abstract

Autophagy has dual effects in human diseases: appropriate autophagy may protect cells from stress, while excessive autophagy may cause cell death. Additionally, close interactions exist between autophagy and the Golgi. This review outlines recent advances regarding the role of the Golgi apparatus in autophagy. The signaling processes of autophagy are dependent on the normal function of the Golgi. Specifically, (i) autophagy-related protein 9 is mainly located in the Golgi and forms new autophagosomes in response to stressors; (ii) Golgi fragmentation is induced by Golgi-related proteins and accompanied with autophagy induction; and (iii) the endoplasmic reticulum-Golgi intermediate compartment and the reticular -Golgi network play essential roles in autophagosome formation to provide a template for lipidation of microtubule-associated protein 1A/1B-light chain 3 and induce further ubiquitination. Golgi-related proteins regulate formation of autophagosomes, and disrupted formation of autophagy can influence Golgi function. Notably, aberrant autophagy has been demonstrated to be implicated in neurological diseases. Thus, targeted therapies aimed at protecting the Golgi or regulating Golgi proteins might prevent or ameliorate autophagy-related neurological diseases. Further studies are needed to investigate the potential application of Golgi therapy in autophagy-based neurological diseases.

摘要

自噬在人类疾病中具有双重作用

适度的自噬可保护细胞免受应激,而过度的自噬则可能导致细胞死亡。此外,自噬与高尔基体之间存在密切的相互作用。本综述概述了高尔基体在自噬中作用的最新进展。自噬的信号传导过程依赖于高尔基体的正常功能。具体而言,(i)自噬相关蛋白9主要位于高尔基体中,并在应激源作用下形成新的自噬体;(ii)高尔基体相关蛋白诱导高尔基体碎片化,并伴随着自噬诱导;(iii)内质网-高尔基体中间腔室和网状高尔基体网络在自噬体形成中起重要作用,为微管相关蛋白1A/1B轻链3的脂化提供模板,并诱导进一步的泛素化。高尔基体相关蛋白调节自噬体的形成,而自噬形成的破坏会影响高尔基体功能。值得注意的是,异常自噬已被证明与神经疾病有关。因此,旨在保护高尔基体或调节高尔基体蛋白的靶向治疗可能预防或改善自噬相关的神经疾病。需要进一步研究以探讨高尔基体治疗在基于自噬的神经疾病中的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ce3/7509445/93ee3ada0635/fcell-08-564975-g001.jpg

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