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自噬与泛素-蛋白酶体系统在骨骼肌萎缩中的动态变化及相互作用。

Dynamics and Interplay between Autophagy and Ubiquitin-proteasome system Coordination in Skeletal Muscle Atrophy.

机构信息

Clinical Biochemistry Laboratory, Department of Biochemistry, Maharshi Dayanand University, Rohtak-124001, Haryana, India.

出版信息

Curr Mol Pharmacol. 2022;15(3):475-486. doi: 10.2174/1874467214666210806163851.

Abstract

Skeletal muscles are considered the largest reservoirs of the protein pool in the body and are critical for the maintenances of body homeostasis. Skeletal muscle atrophy is supported by various physiopathological conditions that lead to loss of muscle mass and contractile capacity of the skeletal muscle. Lysosomal mediated autophagy and ubiquitin-proteasomal system (UPS) concede the major intracellular systems of muscle protein degradation that result in the loss of mass and strength. Both systems recognize ubiquitination as a signal of degradation through different mechanisms, a sign of dynamic interplay between systems. Hence, growing shreds of evidence suggest the interdependency of autophagy and UPS in the progression of skeletal muscle atrophy under various pathological conditions. Therefore, understanding the molecular dynamics and associated factors responsible for their interdependency is necessary for the new therapeutic insights to counteract muscle loss. Based on current literature, the present review summarizes the factors that interplay between autophagy and UPS in favor of enhanced proteolysis of skeletal muscle and how they affect the anabolic signaling pathways under various conditions of skeletal muscle atrophy.

摘要

骨骼肌被认为是体内蛋白质库的最大储存库,对于维持身体内环境稳定至关重要。多种生理病理条件会导致骨骼肌萎缩,从而导致肌肉质量和收缩能力的丧失。溶酶体介导的自噬和泛素-蛋白酶体系统(UPS)是肌肉蛋白降解的主要细胞内系统,导致质量和力量的丧失。这两个系统通过不同的机制识别泛素化作为降解的信号,这是系统之间动态相互作用的标志。因此,越来越多的证据表明,自噬和 UPS 在各种病理条件下骨骼肌萎缩的进展中相互依赖。因此,了解导致它们相互依赖的分子动力学和相关因素对于获得新的治疗见解以对抗肌肉损失是必要的。基于目前的文献,本综述总结了自噬和 UPS 之间相互作用的因素,有利于增强骨骼肌的蛋白水解,以及它们在各种骨骼肌萎缩条件下如何影响合成代谢信号通路。

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