Kwon Junhee, Kim Jihyun, Kim Keun Il
Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic of Korea.
Anim Cells Syst (Seoul). 2023 Feb 23;27(1):29-37. doi: 10.1080/19768354.2023.2181217. eCollection 2023.
Cells activate protective mechanisms to overcome stressful conditions that threaten cellular homeostasis, including imbalances in calcium, redox, and nutrient levels. Endoplasmic reticulum (ER) stress activates an intracellular signaling pathway, known as the unfolded protein response (UPR), to mitigate such circumstances and protect cells. Although ER stress is sometimes a negative regulator of autophagy, UPR induced by ER stress typically activates autophagy, a self-degradative pathway that further supports its cytoprotective role. Sustained activation of ER stress and autophagy is known to trigger cell death and is considered a therapeutic target for certain diseases. However, ER stress-induced autophagy can also lead to treatment resistance in cancer and exacerbation of certain diseases. Since the ER stress response and autophagy affect each other, and the degree of their activation is closely related to various diseases, understanding their relationship is very important. In this review, we summarize the current understanding of two fundamental cellular stress responses, the ER stress response and autophagy, and their crosstalk under pathological conditions to help develop therapies for inflammatory diseases, neurodegenerative disorders, and cancer.
细胞会激活保护机制以克服威胁细胞内稳态的应激条件，包括钙、氧化还原和营养水平的失衡。内质网（ER）应激会激活一种称为未折叠蛋白反应（UPR）的细胞内信号通路，以缓解此类情况并保护细胞。虽然ER应激有时是自噬的负调节因子，但由ER应激诱导的UPR通常会激活自噬，这是一种自我降解途径，进一步支持其细胞保护作用。已知ER应激和自噬的持续激活会触发细胞死亡，并被认为是某些疾病的治疗靶点。然而，ER应激诱导的自噬也可能导致癌症的治疗耐药性和某些疾病的恶化。由于ER应激反应和自噬相互影响，且它们的激活程度与各种疾病密切相关，因此了解它们之间的关系非常重要。在这篇综述中，我们总结了目前对两种基本细胞应激反应，即ER应激反应和自噬，以及它们在病理条件下的相互作用的理解，以帮助开发针对炎症性疾病、神经退行性疾病和癌症的治疗方法。
