Numerous genetic and environmental insults impede the ability of cells to properly fold and posttranslationally modify secretory and transmembrane proteins in the endoplasmic reticulum (ER), leading to a buildup of misfolded proteins in this organelle--a condition called ER stress. ER-stressed cells must rapidly restore protein-folding capacity to match protein-folding demand if they are to survive. In the presence of high levels of misfolded proteins in the ER, an intracellular signaling pathway called the unfolded protein response (UPR) induces a set of transcriptional and translational events that restore ER homeostasis. However, if ER stress persists chronically at high levels, a terminal UPR program ensures that cells commit to self-destruction. Chronic ER stress and defects in UPR signaling are emerging as key contributors to a growing list of human diseases, including diabetes, neurodegeneration, and cancer. Hence, there is much interest in targeting components of the UPR as a therapeutic strategy to combat these ER stress-associated pathologies.

中文翻译：

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内质网应激在人类病理学中的作用。

大量的遗传和环境侮辱阻碍了细胞正确折叠和翻译后修饰内质网（ER）中分泌和跨膜蛋白的能力，从而导致该细胞器中错误折叠的蛋白积聚，这种情况称为ER应激。内质网应激的细胞要生存就必须迅速恢复蛋白质折叠能力，以适应蛋白质折叠需求。在ER中存在高度错误折叠的蛋白时，称为未折叠蛋白应答（UPR）的细胞内信号传导途径会诱导一系列转录和翻译事件，从而恢复ER稳态。但是，如果ER应激长期持续高水平持续存在，则末期UPR计划可确保细胞自我毁灭。慢性内质网应激和普遍定期审议信号中的缺陷正日益成为包括糖尿病，神经退行性疾病和癌症在内的一系列人类疾病的关键因素。因此，将UPR的组成部分作为治疗这些ER应激相关疾病的治疗策略引起了极大的兴趣。