Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications.
Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications.
复制标题
DOI：
10.1111/febs.14608
复制
发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Samali A
中科院分区：
文献类型：
--
作者：
Almanza A;Carlesso A;Chintha C;Creedican S;Doultsinos D;Leuzzi B;Luís A;McCarthy N;Montibeller L;More S;Papaioannou A;Püschel F;Sassano ML;Skoko J;Agostinis P;de Belleroche J;Eriksson LA;Fulda S;Gorman AM;Healy S;Kozlov A;Muñoz-Pinedo C;Rehm M;Chevet E;Samali A
内质网（ER）是细胞内的一种膜性细胞器，是分泌途径的第一区室。因此，ER有助于大约三分之一的细胞蛋白质的产生和折叠，因此与维持细胞稳态和健康与疾病之间的良好平衡密不可分。特定的ER应激信号通路，统称为未折叠蛋白反应（UPR），是维持ER稳态所必需的。当ER蛋白折叠能力被细胞需求压倒时，UPR被触发，并且UPR最初旨在恢复ER稳态和正常细胞功能。然而，如果这失败了，那么UPR就会触发细胞死亡。在这篇综述中，我们提供了以UPR信号为中心的ER功能观点，从ER的发现到对ER和UPR生物学理解的最新进展。我们的评论提供了一个合成的细胞内ER信号围绕蛋白质和UPR，其对其他细胞器和细胞行为的影响，其多方面的和动态的反应，压力和生理学中的作用，最后探索利用这些知识来解决未解决的生物学问题，并解决未满足的生物医学需求。因此，我们提供了一个综合的和全球性的观点，现有的文献ER信号通路及其用于治疗目的。本文综述了内质网（ER）生物学的最新文献，并从信号传导的角度阐述了这些信息。我们不仅涵盖了适应性ER信号传导的基本细胞生物学方面，而且还提供了有关ER应激靶向药物及其在临床中潜在用途的最新发现的信息。
The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one‐third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling‐centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes. The current article reviews the most up‐to‐date literature on Endoplasmic Reticulum (ER) biology and articulates this information from a signalling perspective. Not only do we cover the basic cell biology aspects of adaptive ER signalling but also provide information about the latest discoveries on ER stress targeting drugs and their potential use in the clinic.