肉毒神经毒素抑制剂的研究进展  

Research advances in inhibitors of botulinum neurotoxins

作　　者：谭玲 王建新 王慧 TAN Ling;WANG Jianxin;WANG Hui(State Key Laboratory of Pathogen and Biosecurity,Institute of Microbiology and Epidemiology,Academy of Military Medicine,Academy of Military Sciences,Beijing 100071,China)

机构地区：[1]军事科学院军事医学研究院,微生物流行病研究所,病原微生物生物安全国家重点实验室,北京100071

出　　处：《微生物学报》2022年第4期1270-1285,共16页Acta Microbiologica Sinica

基　　金：国家自然科学基金(82072251)。

摘　　要：肉毒神经毒素(botulinum neurotoxins,BoNTs)是由梭状芽孢杆菌属分泌的外毒素,是目前已知毒性最强的生物类毒素。BoNTs共分为7种血清型(A–G),其中A型导致的肉毒中毒最为常见。由于肉毒毒素的强毒性及易于制备,其已被列为A类生物恐怖制剂。目前,针对肉毒中毒的有效治疗手段为早期注射抗毒素血清。但当毒素进入神经细胞体内后,抗毒素血清作用有限,无法逆转肉毒中毒引起的瘫痪。因此,对于已经发生的肉毒中毒,需要开发更为有效的抗肉毒毒素药物以治疗肉毒中毒。在过去的20年,小分子抑制剂因能克服抗毒素无法在胞内发挥作用的局限性,而成为了新型肉毒中毒治疗药物的热点研发方向。随着肉毒毒素的结构及中毒机制逐渐被阐明,越来越多的相关机制靶点正用于开发有效的抑制剂。因此,本文根据肉毒毒素的中毒机制,综述了近年来报道的一系列小分子肉毒毒素抑制剂的研究进展。Botulinum neurotoxins(BoNTs)secreted by Clostridium are the most toxic biotoxins known.BoNTs are classified into seven serotypes(BoNT/A–G),of which BoNT/A is the most frequent cause of botulism.Due to the strong toxicity and easy preparation,BoNTs are classified as the class A bioterrorism agents.At present,botulism is mainly treated by early administration of antibotulinum serum.However,the antibotulinum serum has limited effect and cannot reverse the paralysis caused by botulism when the toxin enters nerve cells.Therefore,it is necessary to develop more effective drugs for treating botulism.Because small-molecule inhibitors can overcome the limitation that antitoxin cannot neutralize intracellular toxins,they have become a popular direction in the development of novel drugs for treating botulism in the past decades.As the structure of BoNTs and the mechanism of botulism have been gradually elucidated,more and more relevant targets are being used to develop effective inhibitors.This paper reviewed small-molecule inhibitors of BoNTs in recent years according to their mechanisms.

关 键 词：肉毒神经毒素 肉毒中毒 小分子抑制剂 

分 类 号：R595[医药卫生—内科学]