Getting the better of ER stress
Getting the better of ER stress
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DOI：
10.1007/s12079-014-0251-9
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发表时间：
2014-12-01
影响因子：
4.1
通讯作者：
Napoletano, Francesco
中科院分区：
文献类型：
--
作者：
Mollereau, Bertrand;Manie, Serge;Napoletano, Francesco
过去几年的研究强调了未折叠蛋白反应（UPR）在生理和病理条件下最小化累积的错误折叠蛋白的有害影响的能力。内质网（ER）通过扩大其蛋白质折叠能力和刺激自噬和抗氧化反应等保护过程来适应内源性和外源性应激源。虽然很明显严重的内质网应激会导致细胞死亡，但最近的几项研究表明，低水平的内质网应激实际上可能对细胞有益，因为它会引发适应性的UPR，为细胞随后的致命损伤提供“先决条件”；这个过程被称为内质网激效。这一发现对治疗多种与蛋白质平衡缺陷相关的疾病具有重要意义，包括神经退行性疾病、糖尿病和癌症。在这里，我们回顾内质网的生理和病理功能，特别关注导致内质网激效和细胞保护的分子机制，并讨论其对疾病治疗的影响。
Research over the past few years has highlighted the ability of the unfolded protein response (UPR) to minimize the deleterious effects of accumulated misfolded proteins under both physiological and pathological conditions. The endoplasmic reticulum (ER) adapts to endogenous and exogenous stressors by expanding its protein-folding capacity and by stimulating protective processes such as autophagy and antioxidant responses. Although it is clear that severe ER stress can elicit cell death, several recent studies have shown that low levels of ER stress may actually be beneficial to cells by eliciting an adaptive UPR that 'preconditions' the cell to a subsequent lethal insult; this process is called ER hormesis. The findings have important implications for the treatment of a wide variety of diseases associated with defective proteostasis, including neurodegenerative diseases, diabetes, and cancer. Here, we review the physiological and pathological functions of the ER, with a particular focus on the molecular mechanisms that lead to ER hormesis and cellular protection, and discuss the implications for disease treatment.