摘要
凋亡信号调节激酶1(apoptosis signal-regulating kinase 1,ASK1)是丝裂原激活蛋白激酶激酶激酶(mitogen-activated proteinkinase kinases kinase,MAP3K)的家族成员之一,可以响应氧化应激、内质网(endoplasmic reticulum,ER)应激等多种应激刺激,从而激活下游丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)中的c-Jun N末端激酶(c-Jun N-terminal kinase,JNK)和p38丝裂原激活蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)信号通路,调节细胞凋亡、炎症和纤维化,介导急性肾损伤(acute kidney injury,AKI)、糖尿病肾病(diabetic kidney disease,DKD)、心肾综合征(cardiorenal syndrome,CRS)等多种肾脏疾病的进展。本文讨论了ASK1主要的激活和失活机制及其在多种肾脏疾病进展中的作用,对ASK1的抑制剂GS-4997、GS444217和GS459679进行了概述,探究ASK1抑制剂在临床应用中的潜力。
Apoptosis signal-regulating kinase 1(ASK1),a member of the mitogen-activated protein kinase kinase kinase(MAP3K)family,can respond to a variety of stress stimuli,such as oxidative stress and endoplasmic reticulum(ER)stress,thereby activating the c-Jun N-terminal kinase(JNK)and p38 mitogen-activated protein kinase(p38 MAPK)signaling pathways in downstream mitogenactivated protein kinase(MAPK)to regulate apoptosis,inflammation,and fibrosis,mediating acute kidney injury(AKI),diabetic kidney disease(DKD),cardiorenal syndrome(CRS)and other renal diseases.In this review,we discuss the major activation and inactivation mechanisms of ASK1,its role in the progression of multiple renal diseases.We also provide an overview of GS-4997,GS444217 and GS459679,the inhibitors of ASK1,to explore the potential of ASK1 inhibitors in clinical applications.
作者
程苏
李婷婷
王艳茹
邵命海
CHENG Su;LI Tingting;WANG Yanru;SHAO Minghai(Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,201203;TCM Institute of Kidney Disease,Shanghai University of Traditional Chinese Medicine,Shanghai,201203;Key Laboratory of Liver and Kidney Diseases,Ministry of Education,Shanghai University of Traditional Chinese Medicine,Shanghai,201203;Shanghai Key Laboratory of Traditional Chinese Clinical Medicine,Shanghai,201203)
出处
《基因组学与应用生物学》
CAS
CSCD
北大核心
2024年第1期1-8,共8页
Genomics and Applied Biology
基金
国家自然科学基金项目(81973807)资助。
