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Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology
Pharmacological Reviews ( IF 21.1 ) Pub Date : 2017-04-01 , DOI: 10.1124/pr.116.012658
Marco Pirazzini , Ornella Rossetto , Roberto Eleopra , Cesare Montecucco

The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology.



中文翻译:

肉毒杆菌神经毒素:生物学,药理学和毒理学

肉毒杆菌神经毒素(BoNT)的研究在许多方面都在迅速发展。由于新一代测序,正在发现新型BoNT,但它们的生物学和药理特性仍然未知。已经确定了毒素与辅助蛋白形成的大蛋白复合物的分子结构,这些复合物已包含在某些BoNT A1型和B1型药物制剂中。迄今为止,最大的努力一直致力于在越来越多的应用(包括疼痛治疗)中对作为治疗剂的BoNT进行测试和验证。BoNT A1型也已被单独或与其他药物联合用于多种美容治疗中,这一特定市场已达到专门用于治疗医学综合征的市场规模。BoNTs的药理特性和作用方式阐明了神经元转运和蛋白质-蛋白质相互作用的一般原理,并正在刺激基础科学研究。而且,发现和将要发现的各种各样的BoNT以及具有特定特性的重组BoNT的生产表明在疾病/症状特异性增加的疗法中的新用途。本文对这些最新进展进行了综述,以提供有关BoNT作用的生物学机制,其在药理学和化妆品中的日益使用以及其毒理学的最新情况。人们发现和发现的BoNT种类繁多,并且具有特定特性的重组BoNT的生产表明在疾病/症状特异性增加的治疗方法中的新用途。本文对这些最新进展进行了综述,以提供有关BoNT作用的生物学机制,其在药理学和化妆品中的日益使用以及其毒理学的最新情况。人们发现和发现的BoNT种类繁多,并且具有特定特性的重组BoNT的生产表明在疾病/症状特异性增加的治疗方法中的新用途。本文对这些最新进展进行了综述,以提供有关BoNT作用的生物学机制,其在药理学和化妆品中的日益使用以及其毒理学的最新情况。

更新日期:2017-08-24
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