Biotechnology Division, Defence Research & Development Establishment, Gwalior, India.
Indian J Med Res. 2010 Nov;132(5):489-503.
Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility . It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin.
肉毒梭菌神经毒素是人类肉毒中毒的病原体,由厌氧孢子形成的革兰氏阳性杆菌——肉毒梭菌产生。由于其极高的效力和致命性、易于生产、运输和滥用以及受影响者需要长期强化护理,肉毒梭菌神经毒素构成了重大的生物武器威胁。一克结晶毒素,均匀分散并吸入,就能杀死超过一百万人。肉毒毒素具有惊人效力的基础是酶学的;该毒素是一种锌蛋白酶,可将负责乙酰胆碱释放到神经肌肉接头的神经元囊泡相关蛋白切割。作为一种军事或恐怖主义武器,肉毒梭菌毒素可通过气溶胶传播,或通过污染水或食物供应传播,造成广泛的人员伤亡。近年来,肉毒毒素研究的一个迷人方面是将最有效的毒素开发成具有重要治疗用途的分子。它是第一个获得许可用于治疗人类疾病的生物毒素。20 世纪 80 年代末,加拿大批准使用该毒素治疗斜视,2001 年用于消除面部皱纹,2002 年,美国食品和药物管理局紧随其后。本综述重点介绍了肉毒梭菌神经毒素的战争潜力和医疗用途。