Gastroenterology & Hepatology, Tulane University School of Medicine, New Orleans, Lousiana, USA.
Medicine, Division of Gastroenterology, UTHSC COM, Memphis, Tennessee, USA.
J Investig Med. 2021 Feb;69(2):309-315. doi: 10.1136/jim-2020-001570. Epub 2021 Jan 19.
The ability of translated cellular proteins to perform their functions requires their proper folding after synthesis. The endoplasmic reticulum (ER) is responsible for coordinating protein folding and maturation. Infections, genetic mutations, environmental factors and many other conditions can lead to challenges to the ER known as ER stress. Altering ER homeostasis results in accumulation of misfolded or unfolded proteins. To eliminate this problem, a response is initiated by the cell called the unfolded protein response (UPR), which involves multiple signaling pathways. Prolonged ER stress or a dysregulated UPR can lead to premature apoptosis and an exaggerated inflammatory response. Following these discoveries, ER stress was shown to be related to several chronic diseases, such as diabetes mellitus, neurodegenerative disorders, fatty liver disease and inflammatory bowel disease that have not yet been clearly demonstrated pathophysiologically. Here, we review the field and present up-to-date information on the relationship between biological processing, ER stress, UPR, and several chronic diseases.
翻译后的细胞蛋白能否发挥其功能，取决于其合成后的正确折叠。内质网（ER）负责协调蛋白质的折叠和成熟。感染、基因突变、环境因素和许多其他条件都可能导致内质网（ER）出现应激，即内质网应激（ER stress）。内质网稳态的改变会导致错误折叠或未折叠蛋白质的积累。为了解决这个问题，细胞会启动一种称为未折叠蛋白反应（UPR）的反应，其中涉及多个信号通路。内质网应激持续或未调节的 UPR 会导致细胞凋亡过早和炎症反应过度。在这些发现之后，内质网应激被证明与几种慢性疾病有关，如糖尿病、神经退行性疾病、脂肪肝疾病和炎症性肠病，但其病理生理学尚未得到明确证实。在这里，我们综述了这一领域，并提供了有关生物处理、内质网应激、UPR 与几种慢性疾病之间关系的最新信息。
