蛋白降解靶向嵌合体在急性肾损伤中的研究进展

Research advances of proteolysis targeting chimeras for acute kidney injury

急性肾损伤(acute kidney injury,AKI)是一组以肾功能急剧下降为特征的肾脏疾病。AKI不仅病死率高,急性期后肾脏适应不良或不完全修复还会导致肾纤维化,最终发展成慢性肾脏病。目前尚无有效措施来限制损伤、促进恢复和提高生存率。蛋白降解靶向嵌合体(proteolysis tar-geting chimeras,PROTACs)利用泛素蛋白酶体系统降解目标蛋白,为AKI药物研发提供了新的策略。本文总结了AKI有前景的治疗靶点及PROTACs技术在AKI中的应用。

Acute kidney injury(AKI)is a diverse group of renal diseases characterized by a dramatic decline in renal function.Not only AKI has a high mortality rate,but also poor renal adaptation or incomplete repair after acute phase may also lead to renal fibrosis and eventually to chronic kidney disease(CKD).Currently there are no effective measures for limiting damage,promoting recovery and improving survival.Proteolysis targeting chimeras(PROTACs)provide a novel strategy for AKI drug development through ubiquitin-proteasome system of degrading target proteins.This review summarized promising therapeutic targets for AKI and the application of PROTACs technology.