Eubanks Lisa M, Dickerson Tobin J
The Scripps Research Institute, Department of Chemistry, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Future Microbiol. 2007 Dec;2(6):677-87. doi: 10.2217/17460913.2.6.677.
Botulinum neurotoxin (BoNT) has recently catapulted into the public consciousness in two seemingly disparate roles: potential use as a biological weapon and treatment of neuromuscular disorders. This bacterially produced protein is the most potent toxin known to humans, with a lethal dose estimated at approximately 1 ng/kg of body weight. BoNT intoxication occurs via a multistep process that includes recognition of peripheral neuronal cell membrane receptors, endocytosis and translocation of the light chain metalloprotease into the cytosol, and catalytic cleavage of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins critical for vesicle fusion and neurotransmitter release. Each of these distinct steps has been studied at the molecular level and is a valid target for the development of pharmacological interventions to prevent the considerable mortality associated with botulism. Alternatively, clinical uses of BoNT continue to expand at an ever-increasing rate; however, further optimization of BoNT therapy is critical to maximize efficacy.
肉毒杆菌神经毒素（BoNT）最近以两种看似截然不同的角色迅速进入公众视野：作为生物武器的潜在用途以及治疗神经肌肉疾病。这种由细菌产生的蛋白质是人类已知的最强大毒素，估计致死剂量约为1纳克/千克体重。BoNT中毒通过一个多步骤过程发生，包括识别外周神经元细胞膜受体、轻链金属蛋白酶的内吞作用和转运到细胞质中，以及对囊泡融合和神经递质释放至关重要的可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白的催化裂解。这些不同步骤中的每一个都已在分子水平上进行了研究，并且是开发预防与肉毒中毒相关的高死亡率的药理学干预措施的有效靶点。另外，BoNT的临床应用继续以不断增加的速度扩展；然而，进一步优化BoNT治疗对于最大化疗效至关重要。
