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蛋白质稳态与恢复力:关于个体应激与细胞内应激的中间阶段

Proteostasis and resilience: on the interphase between individual's and intracellular stress.

作者信息

Díaz-Hung Mei-Li, Hetz Claudio

机构信息

Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health and Metabolism, Santiago, Chile.

Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health and Metabolism, Santiago, Chile; Buck Institute for Research on Aging, Novato, CA, USA.

出版信息

Trends Endocrinol Metab. 2022 May;33(5):305-317. doi: 10.1016/j.tem.2022.02.003. Epub 2022 Mar 22.

Abstract

A long proportion of the population is resilient to the negative consequences of stress. Glucocorticoids resulting from endocrine responses to stress are essential adaptive mediators, but also drive alterations to brain function, negatively impacting neuronal connectivity, synaptic plasticity, and memory-related processes. Recent evidence has indicated that organelle function and cellular stress responses are relevant determinant of vulnerability and resistance to environmental stress. At the molecular level, a fundamental mechanism of cellular stress adaptation is the maintenance of proteostasis, which also have key roles in sustaining basal neuronal function. Here, we discuss recent evidence suggesting that proteostasis unbalance at the level of the endoplasmic reticulum, the main site for protein folding in the cell, represents a possible mechanistic link between individuals and cellular stress.

摘要

很大一部分人口能够抵御压力带来的负面影响。内分泌系统对应激产生的糖皮质激素是重要的适应性介质,但也会导致大脑功能改变,对神经元连接、突触可塑性和记忆相关过程产生负面影响。最近的证据表明,细胞器功能和细胞应激反应是易受环境应激影响和具备抵抗力的相关决定因素。在分子水平上,细胞应激适应的一个基本机制是维持蛋白质稳态,这在维持基础神经元功能方面也起着关键作用。在此,我们讨论最近的证据,这些证据表明,作为细胞内蛋白质折叠主要场所的内质网水平上的蛋白质稳态失衡,可能是个体应激与细胞应激之间的一种机制联系。

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