Rossetto O, Seveso M, Caccin P, Schiavo G, Montecucco C
Centro CNR Biomembrane and Dipartmento de Scienze Biomediche, Università de Padova, Italy.
Toxicon. 2001 Jan;39(1):27-41. doi: 10.1016/s0041-0101(00)00163-x.
The neuroparalytic syndromes of tetanus and botulism are caused by neurotoxins produced by bacteria of the genus Clostridium. They are 150 kDa proteins consisting of three-domains, endowed with different functions: neurospecific binding, membrane translocation and specific proteolysis of three key components of the neuroexocytosis apparatus. After binding to the presynaptic membrane of motoneurons, tetanus neurotoxin (TeNT) is internalized and transported retroaxonally to the spinal cord, where it blocks neurotransmitter release from spinal inhibitory interneurons. In contrast, the seven botulinum neurotoxins (BoNT) act at the periphery and inhibit acetylcholine release from peripheral cholinergic nerve terminals. TeNT and BoNT-B, -D, -F and -G cleave specifically at single but different peptide bonds, VAMP/synaptobrevin, a membrane protein of small synaptic vesicles. BoNT types -A, -C and -E cleave SNAP-25 at different sites within the COOH-terminus, whereas BoNT-C also cleaves syntaxin. BoNTs are increasingly used in medicine for the treatment of human diseases characterized by hyperfunction of cholinergic terminals.
破伤风和肉毒中毒的神经麻痹综合征是由梭菌属细菌产生的神经毒素引起的。它们是由三个结构域组成的150 kDa蛋白质，具有不同的功能：神经特异性结合、膜转位以及对神经外排装置三个关键成分的特异性蛋白水解。破伤风神经毒素（TeNT）与运动神经元的突触前膜结合后，被内化并逆行轴突运输至脊髓，在脊髓中它会阻断脊髓抑制性中间神经元释放神经递质。相比之下，七种肉毒杆菌神经毒素（BoNT）作用于外周，抑制外周胆碱能神经末梢释放乙酰胆碱。TeNT和BoNT-B、-D、-F及-G特异性切割单个但不同的肽键，即小突触囊泡的膜蛋白VAMP/突触小泡蛋白。A型、C型和E型BoNT在COOH末端的不同位点切割SNAP-25，而C型BoNT也切割 syntaxin。BoNT越来越多地用于医学治疗以胆碱能末梢功能亢进为特征的人类疾病。
