Department of Virology (a Unit of Department of Microbiology), Vallabhbhai Patel Chest Institute, University of Delhi, Delhi-110007, India.
Department of Biomedical Science, Acharya Narendra Dev College, University of Delhi, Kalkaji, New Delhi-110019, India.
Expert Rev Mol Med. 2021 Mar 4;23:e1. doi: 10.1017/erm.2021.2.
Unfolded protein response (UPR) is an evolutionarily conserved pathway triggered during perturbation of endoplasmic reticulum (ER) homeostasis in response to the accumulation of unfolded/misfolded proteins under various stress conditions like viral infection, diseased states etc. It is an adaptive signalling cascade with the main purpose of relieving the stress from the ER, which may otherwise lead to the initiation of cell death via apoptosis. ER stress if prolonged, contribute to the aetiology of various diseases like cancer, type II diabetes, neurodegenerative diseases, viral infections etc. Understanding the role of UPR in disease progression will help design pharmacological drugs targeting the sensors of signalling cascade acting as potential therapeutic agents against various diseases. The current review aims at highlighting the relevance of different pathways of UPR in disease progression and control, including the available pharmaceutical interventions responsible for ameliorating diseased state via modulating UPR pathways.
未折叠蛋白反应 (UPR) 是一种进化上保守的途径,在各种应激条件下,如病毒感染、疾病状态等,内质网 (ER) 稳态受到干扰时,会触发该途径,以应对未折叠/错误折叠蛋白的积累。它是一种适应性信号级联反应,主要目的是减轻 ER 的压力,否则这可能会通过细胞凋亡引发细胞死亡。如果 ER 应激持续存在,会导致各种疾病的发病机制,如癌症、II 型糖尿病、神经退行性疾病、病毒感染等。了解 UPR 在疾病进展中的作用将有助于设计针对信号级联传感器的药理学药物,这些传感器作为针对各种疾病的潜在治疗剂。本综述旨在强调 UPR 不同途径在疾病进展和控制中的相关性,包括通过调节 UPR 途径改善疾病状态的现有药物干预措施。