Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, SA, Italy.
Pineta Grande Hospital, Via Domiziana, km 30/00, 81030 Castel Volturno, CE, Italy.
Int J Mol Sci. 2022 Dec 22;24(1):185. doi: 10.3390/ijms24010185.
The endoplasmic reticulum (ER) is a dynamic structure, playing multiple roles including calcium storage, protein synthesis and lipid metabolism. During cellular stress, variations in ER homeostasis and its functioning occur. This condition is referred as ER stress and generates a cascade of signaling events termed unfolded protein response (UPR), activated as adaptative response to mitigate the ER stress condition. In this regard, calcium levels play a pivotal role in ER homeostasis and therefore in cell fate regulation since calcium signaling is implicated in a plethora of physiological processes, but also in disease conditions such as neurodegeneration, cancer and metabolic disorders. A large body of emerging evidence highlighted the functional role of TRP channels and their ability to promote cell survival or death depending on endoplasmic reticulum stress resolution, making them an attractive target. Thus, in this review we focused on the TRP channels' correlation to UPR-mediated ER stress in disease pathogenesis, providing an overview of their implication in the activation of this cellular response.
内质网（ER）是一种动态结构，具有多种功能，包括钙储存、蛋白质合成和脂质代谢。在细胞应激时，内质网的稳态及其功能会发生变化。这种情况被称为内质网应激，并产生一系列被称为未折叠蛋白反应（UPR）的信号级联反应，作为适应反应被激活以减轻内质网应激状态。在这方面，钙水平在内质网稳态和细胞命运调节中起着关键作用，因为钙信号参与了许多生理过程，但也与神经退行性疾病、癌症和代谢紊乱等疾病状态有关。大量新出现的证据强调了 TRP 通道的功能作用及其根据内质网应激解决情况促进细胞存活或死亡的能力，这使它们成为一个有吸引力的靶点。因此，在这篇综述中，我们重点关注了 TRP 通道与 UPR 介导的内质网应激在疾病发病机制中的相关性，概述了它们在激活这种细胞反应中的作用。
