1] Biomedical Neuroscience Institute, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, 1027 Independencia, PO Box 70086, Santiago, Chile. [2] Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, Boston, Massachusetts 02115, USA.
Nat Rev Drug Discov. 2013 Sep;12(9):703-19. doi: 10.1038/nrd3976.
Stress induced by the accumulation of unfolded proteins in the endoplasmic reticulum (ER) is a feature of specialized secretory cells and is also observed in many diseases, including cancer, diabetes, autoimmune conditions, liver disorders, obesity and neurodegenerative disorders. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response, which is an integrated signal transduction pathway that modulates many aspects of ER physiology. When these mechanisms of adaptation are insufficient to handle the unfolded protein load, cells undergo apoptosis. Here, we discuss recent advances in the design of novel compounds and therapeutic strategies to manipulate levels of ER stress in disease.
内质网（ER）中未折叠蛋白的积累所导致的应激是特化分泌细胞的一个特征，也存在于许多疾病中，包括癌症、糖尿病、自身免疫性疾病、肝脏疾病、肥胖症和神经退行性疾病。细胞通过未折叠蛋白反应的激活来适应 ER 应激，这是一种整合的信号转导途径，调节 ER 生理学的许多方面。当这些适应机制不足以处理未折叠蛋白负荷时，细胞就会发生凋亡。在这里，我们讨论了设计新型化合物和治疗策略来调节疾病中 ER 应激水平的最新进展。
