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泛素蛋白酶体系统在肌肉萎缩中的作用及潜在治疗靶点

Roles and potential therapeutic targets of the ubiquitin proteasome system in muscle wasting.

作者信息

Nury David, Doucet Christine, Coux Olivier

机构信息

CRBM-CNRS UMR5237, IFR22, 1919 route de Mende, 34000 Montpellier, France.

出版信息

BMC Biochem. 2007 Nov 22;8 Suppl 1(Suppl 1):S7. doi: 10.1186/1471-2091-8-S1-S7.

DOI:10.1186/1471-2091-8-S1-S7
PMID:18047744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2106371/
Abstract

Muscle wasting, characterized by the loss of protein mass in myofibers, is in most cases largely due to the activation of intracellular protein degradation by the ubiquitin proteasome system (UPS). During the last decade, mechanisms contributing to this activation have been unraveled and key mediators of this process identified. Even though much remains to be understood, the available information already suggests screens for new compounds inhibiting these mechanisms and highlights the potential for pharmaceutical drugs able to treat muscle wasting when it becomes deleterious. This review presents an overview of the main pathways contributing to UPS activation in muscle and describes the present state of efforts made to develop new strategies aimed at blocking or slowing muscle wasting. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).

摘要

肌肉萎缩的特征是肌纤维中蛋白质质量的丧失,在大多数情况下,这主要是由于泛素蛋白酶体系统(UPS)激活细胞内蛋白质降解所致。在过去十年中,导致这种激活的机制已被阐明,这一过程的关键介质也已被确定。尽管仍有许多有待了解的地方,但现有信息已经表明可以筛选抑制这些机制的新化合物,并凸显了在肌肉萎缩变得有害时能够治疗它的药物的潜力。本综述概述了导致肌肉中UPS激活的主要途径,并描述了为开发旨在阻止或减缓肌肉萎缩的新策略所做努力的现状。出版历史:从Current BioData的靶向蛋白质数据库(TPdb;http://www.targetedproteinsdb.com)重新发布。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b92/2106371/d9fc368cdacb/1471-2091-8-S1-S7-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b92/2106371/d9fc368cdacb/1471-2091-8-S1-S7-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b92/2106371/d9fc368cdacb/1471-2091-8-S1-S7-1.jpg

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Drug discovery in the ubiquitin-proteasome system.泛素-蛋白酶体系统中的药物发现
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Myostatin regulation of muscle development: molecular basis, natural mutations, physiopathological aspects.
小分子 PSSM0332 可使 CRL4A E3 连接酶复合物解体,减少 NcoR1 的泛素化,从而抑制脓毒症诱导的小鼠心肌功能障碍模型中的炎症反应。
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