内质网(ER)是蛋白质质量控制的关键,其功能的破坏会导致各种疾病。内质网应激引发一种称为未折叠蛋白反应(UPR)的适应性反应,可以恢复细胞稳态或诱导细胞死亡。褪黑激素,一个安全和多功能的化合物,显示出控制ER应激的希望,并且可能是管理UPR的有价值的治疗剂。通过调节内质网和线粒体功能,褪黑激素有助于通过减少氧化应激来维持细胞稳态,炎症,和凋亡。褪黑素可以直接或间接干扰ER相关传感器和UPR的下游目标,影响细胞死亡,自噬,炎症,分子修复,在其他人中。至关重要的是,本文综述了褪黑素在包括肝损伤在内的各种疾病中对ER应激的机制作用,神经变性,生殖障碍,肺部疾病,心肌病,胰岛素抵抗,肾功能不全,和癌症。有趣的是,虽然它减轻了大多数病理背景下的ER压力负担,它可以矛盾地刺激癌细胞的内质网应激,突出了它在细胞稳态中的复杂参与。通过使用体内和体外模型的大量成功研究,继续进行临床试验对于充分探索褪黑素在这些疾病中的治疗潜力至关重要.
The endoplasmic reticulum (ER) is crucial for protein quality control, and disruptions in its function can lead to various diseases. ER stress triggers an adaptive response called the unfolded protein response (UPR), which can either restore cellular homeostasis or induce cell death. Melatonin, a safe and multifunctional compound, shows promise in controlling ER stress and could be a valuable therapeutic agent for managing the UPR. By regulating ER and mitochondrial functions, melatonin helps maintain cellular homeostasis via reduction of oxidative stress, inflammation, and apoptosis. Melatonin can directly or indirectly interfere with ER-associated sensors and downstream targets of the UPR, impacting cell death, autophagy, inflammation, molecular repair, among others. Crucially, this
review explores the mechanistic role of melatonin on ER stress in various diseases including liver damage, neurodegeneration, reproductive disorders, pulmonary disease, cardiomyopathy, insulin resistance, renal dysfunction, and cancer. Interestingly, while it alleviates the burden of ER stress in most pathological contexts, it can paradoxically stimulate ER stress in cancer cells, highlighting its intricate involvement in cellular homeostasis. With numerous successful studies using in vivo and in vitro models, the continuation of clinical trials is imperative to fully explore melatonin\'s therapeutic potential in these conditions.