Wu Fa-Ling, Liu Wen-Yue, Van Poucke Sven, Braddock Martin, Jin Wei-Min, Xiao Jian, Li Xiao-Kun, Zheng Ming-Hua
a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
b Institute of Hepatology , Wenzhou Medical University , Wenzhou , China.
Expert Rev Gastroenterol Hepatol. 2016 Sep;10(9):1041-52. doi: 10.1080/17474124.2016.1179575. Epub 2016 May 3.
The accumulation of unfolded protein in the endoplasmic reticulum (ER) initiates an unfolded protein response (UPR) via three signal transduction cascades, which involve protein kinase RNA-like ER kinase (PERK), inositol requiring enzyme-1α (IRE1α) and activating transcription factor-6α (ATF6α). An ER stress response is observed in nearly all physiologies related to acute and chronic liver disease and therapeutic targeting of the mechanisms implicated in UPR signaling have attracted considerable attention.
This review focuses on the correlation between ER stress and liver disease and the possible targets which may drive the potential for novel therapeutic intervention. Expert Commentary: We describe pathways which are involved in UPR signaling and their potential correlation with various liver diseases and underlying mechanisms which may present opportunities for novel therapeutic strategies are discussed.
内质网(ER)中未折叠蛋白的积累通过三种信号转导级联反应引发未折叠蛋白反应(UPR),这涉及蛋白激酶RNA样内质网激酶(PERK)、肌醇需求酶-1α(IRE1α)和激活转录因子-6α(ATF6α)。在几乎所有与急慢性肝病相关的生理过程中都观察到内质网应激反应,并且针对UPR信号传导相关机制的治疗靶点已引起了相当大的关注。
本综述重点关注内质网应激与肝病之间的相关性以及可能推动新型治疗干预潜力的潜在靶点。专家评论:我们描述了参与UPR信号传导的途径及其与各种肝病的潜在相关性,并讨论了可能为新型治疗策略提供机会的潜在机制。