摘要
神经退行性疾病(neurodegenerative disorders,NDs)是一类引起神经细胞损伤或导致运动性、认知性功能障碍的疾病,其中一个最主要的病理特征为患者大脑中出现异常折叠的蛋白质聚集物,目前缺乏积极有效的药物用于NDs的治疗。而蛋白水解靶向嵌合体(proteolysis-targeting chimera,PROTAC)是一种双功能的小分子化合物,它可以将靶蛋白和E3泛素连接酶招募形成三元复合物,然后通过泛素蛋白酶体系统(ubiquitin-proteasome system,UPS)实现对靶蛋白的降解。理论上该技术有望靶向降解不可成药蛋白,因此在NDs研究中具有巨大潜力和发展空间,目前也受到了广泛关注。因此笔者对PROTAC技术进行了简要介绍,主要综述了其在NDs中的应用,并总结了PROTAC在NDs中应用的优势和挑战。
Neurodegenerative disorders(NDs)are a class of diseases that cause neural cell damage or motor and cognitive dysfunction.One of the most important pathological features is the misfolded protein aggregates in the patient's brain.There is currently a lack of active and effective drugs for the treatment of NDs.Proteolysis-targeting chimera(PROTAC)is a bifunctional small molecule compound,which can recruit the target protein and E3 ubiquitin ligase to form a ternary complex,and then degrade the target protein by the ubiquitin-proteasome system(UPS).Theoretically,it is expected to target and degrade undruggable proteins,so it has great potential and development space in the research of NDs,and it has also received extensive attention.This paper briefly introduces the PROTAC technology,mainly reviews its application in NDs,and summarizes the advantages and challenges of the application of PROTAC in NDs.
作者
刘鹏
曹端源
罗金重
谢赛赛
刘婧
LIU Peng;CAO Duanyuan;LUO Jinchong;XIE Saisai;LIU Jing(National Pharmaceutical Engineering Research Center for Solid Preparation in Chinese Herbal Medicine,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;School of Pharmacy,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2023年第19期1721-1730,共10页
Chinese Pharmaceutical Journal
基金
国家自然科学基金项目资助(81760622,21807052)
江西省科技创新杰出青年人才培养计划资助(20192BCB23018)
江西省自然科学基金项目资助(20192ACBL21034,20202BAB216042)
江西省教育厅项目资助(GJJ190673)。
关键词
蛋白水解靶向嵌合体
神经退行性疾病
蛋白质降解
泛素-蛋白酶体系统
双功能分子
proteolysis-targeting chimera(PROTAC)
neurodegenerative disorders(NDs)
protein degradation
ubiquitin-proteasome system
bifunctional molecule
作者简介
刘鹏,男,硕士研究生研究方向:药物化学;通讯作者:谢赛赛,男,博士,教授研究方向:药物化学Tel:(0791)87119623;通讯作者:刘婧,女,硕士,副教授研究方向:中药制剂学Tel:(0791)87119623。
