内质网应激与疾病

内质网是蛋白质合成与折叠、维持Ca²⁺动态平衡及合成脂类和固醇的场所。遗传或环境损伤引起内质网功能紊乱导致内质网应激,激活未折叠蛋白反应。未折叠蛋白反应是一种细胞自我保护性措施,但是内质网应激过强或持续时间过久可引起细胞凋亡。因此,内质网应激与众多人类疾病的发生发展密切相关。最近研究证明,癌症、炎症性疾病、代谢性疾病、骨质疏松症及神经退行性疾病等有内质网应激信号传递参与。然而内质网应激作为一个有效靶点参与各种疾病发挥作用的功能和机制仍然有待进一步研究。在近年来发表的文献基础上对内质网应激与疾病的关系,以及其可能的作用机制进行综述。

Role of Endoplasmic Reticulum Stress in Diseases

Endoplasmic reticulum (ER) is the site of protein synthesis, protein folding, maintainance of calcium homeostasis, synthesis of lipids and sterols. Genetic or environmental insults can alter its function generating ER stress. During ERS, protein misfolding and accumulation in the ER lumen initiate unfolded protein response(UPR) through a series of signal transduction pathways that produce various effects, including enhancing the ability of proteins to fold properly, accelerating protein degradation, increasing the probability of cell survival, and strengthening the selfrepair ability of the ER. Either ERS persists or activated excessively, eventually initiates cell apoptosis. Therefore, ER stress and UPR are implicated in the development of various diseases. Recent studies have demonstrated that ER stress and UPR signaling are involved in cancer, inflammatory diseases, metabolic disorders, osteoporosis and neurodegenerative diseases. However, the precise knowledge regarding involvement of ER stress in different disease processes is still debatable. Here the possible role of ER stress in various disorders on the basis of existing literature is discussed.