肽酰基精氨酸脱亚氨酶4(PAD4)的功能及其小分子抑制剂的研究进展  

Research progress of PAD4 function and its small molecule inhibitors

作　　者：谢万生 李仲洋 周瑞怡 李耀华 常丽梅 XIE Wan-sheng;LI Zhong-yang;ZHOU Rui-yi;LI Yao-hua;CHANG Li-mei(Hainan Provincial Drug and Medical Device Evaluation Service Center,Haikou 570216,China;Medical Device Technology Review Center,National Medical Products Administration,Beijing 100037,China)

机构地区：[1]海南省药品和医疗器械审评服务中心,海南海口570216 [2]国家药品监督管理局医疗器械技术审评中心,北京100037

出　　处：《现代药物与临床》2021年第6期1322-1329,共8页Drugs & Clinic

摘　　要：肽酰基精氨酸脱亚氨酶4(peptidylarginine deiminase 4,PAD4)依赖钙离子催化精氨酸残基向目标蛋白瓜氨酸残基转化的过程,是一种翻译后修饰,被称为瓜氨酸化。PAD4通过组蛋白瓜氨酸化调节基因转录活性诱导人类疾病的发生、发展。综述了PAD4在自身免疫性疾病、肿瘤、急性冠状动脉综合征中的作用,总结了PAD4抑制剂介导蛋白质瓜氨酸化的生物学作用的可能机制,归纳了PAD4特异性抑制剂治疗类风湿关节炎和其他疾病的临床效用,讨论了PAD4及其抑制剂对自身免疫性疾病和癌症的潜在治疗价值。Peptidylarginine deiminase4 relies on calcium ions to catalyze the conversion of arginine residues to citrulline residues of the target protein.This is a post-translational modification called citrullination.PAD4 regulates gene transcription activity through histone citrullination to induce the occurrence and development of human diseases.In this review,we summarized the role of PAD4 in autoimmune diseases,tumors,and acute coronary syndromes,and the possible mechanisms of the biological effects of PAD4 inhibitors mediating protein citrullination.The clinical utility of PAD4 specific inhibitors in the treatment of rheumatoid arthritis and other diseases were discussed.In addition,we summarized and discussed the potential therapeutic value of PAD4 and its inhibitors for disease diagnosis and treatment of autoimmune diseases and cancers.

关 键 词：肽酰基精氨酸脱亚氨酶4(PAD4) PAD4抑制剂 自身免疫性疾病 癌症 急性冠状动脉综合征 

分 类 号：R977[医药卫生—药品]