Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most potent toxins known and cause botulism and tetanus, respectively. BoNTs are also widely utilized as therapeutic toxins. They contain three functional domains responsible for receptor-binding, membrane translocation, and proteolytic cleavage of host proteins required for synaptic vesicle exocytosis. These toxins also have distinct features: BoNTs exist within a progenitor toxin complex (PTC), which protects the toxin and facilitates its absorption in the gastrointestinal tract, whereas TeNT is uniquely transported retrogradely within motor neurons. Our increasing knowledge of these toxins has allowed the development of engineered toxins for medical uses. The discovery of new BoNTs and BoNT-like proteins provides additional tools to understand the evolution of the toxins and to engineer toxin-based therapeutics. This review summarizes the progress on our understanding of BoNTs and TeNT, focusing on the PTC, receptor recognition, new BoNT-like toxins, and therapeutic toxin engineering.

中文翻译：

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肉毒杆菌和破伤风神经毒素。

肉毒杆菌神经毒素（BoNTs）和破伤风神经毒素（TeNT）是已知最有效的毒素，分别导致肉毒中毒和破伤风。BoNT也被广泛用作治疗毒素。它们包含三个功能域，负责受体结合，膜易位和突触囊泡胞吐作用所需的宿主蛋白的蛋白水解裂解。这些毒素也具有独特的特征：BoNT存在于祖毒素复合物（PTC）中，该复合物保护该毒素并促进其在胃肠道中的吸收，而TeNT在运动神经元内独特地逆行转运。我们对这些毒素的了解越来越多，因此可以开发出用于医学用途的工程毒素。新的BoNT和类似BoNT的蛋白质的发现为了解毒素的进化和设计基于毒素的疗法提供了额外的工具。这篇综述总结了我们对BoNT和TeNT的理解，重点是PTC，受体识别，新型BoNT样毒素和治疗性毒素工程学。