未折叠蛋白反应：机体稳态的传感器和协调器。
The UPR: Sensor and Coordinator of Organismal Homeostasis.
机构信息
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; The Glenn Center for Aging Research at UC Berkeley, Berkeley, CA 94720, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; The Glenn Center for Aging Research at UC Berkeley, Berkeley, CA 94720, USA.
出版信息
Mol Cell. 2017 Jun 15;66(6):761-771. doi: 10.1016/j.molcel.2017.05.031.
Life is stressful. Organisms are repeatedly exposed to stressors that disrupt protein homeostasis (proteostasis), resulting in protein misfolding and aggregation. To sense and respond to proteotoxic perturbations, cells have evolved compartment-specific stress responses, such as the unfolded protein response of the endoplasmic reticulum (UPR). However, UPR function is impaired with age, which, we propose, creates a permissive environment for protein aggregation, unresolved ER stress, and chronic inflammation. Understanding age-related changes to the UPR will provide new avenues for therapeutic intervention in metabolic disease, neurodegeneration, and aging.
生活充满压力。生物体反复受到破坏蛋白质平衡（稳态）的应激源的影响，导致蛋白质错误折叠和聚集。为了感知和应对蛋白毒性的干扰，细胞已经进化出具有特定区域功能的应激反应，例如内质网的未折叠蛋白反应（UPR）。然而，随着年龄的增长，UPR 的功能会受到损害，我们认为这为蛋白质聚集、未解决的内质网应激和慢性炎症创造了一个许可的环境。了解 UPR 与年龄相关的变化将为代谢性疾病、神经退行性疾病和衰老的治疗干预提供新的途径。
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