Tetanus and botulinum neurotoxins: turning bad guys into good by research

The neuroparalytic syndromes of tetanus and botulism are caused by neurotox ins produced by bacteria of the genus Clostridium. They are 150 kDa protein s consisting of three-domains, endowed with different functions: neurospeci fic binding, membrane translocation and specific proteolysis of three key c omponents of the neuroexocytosis apparatus. After binding to the presynapti c membrane of motoneurons, tetanus neurotoxin (TeNT) is internalized and tr ansported retroaxonally to the spinal cord, where it blocks neurotransmitte r release from spinal inhibitory interneurons. In contrast, the seven botul inum neurotoxins (BoNT) act at the periphery and inhibit acetylcholine rele ase from peripheral cholinergic nerve terminals. TeNT and BoNT-B, -D, -F an d -G cleave specifically at single but different peptide bonds, VAMP/synapt obrevin, a membrane protein of small synaptic vesicles. BoNT types -A, -C a nd -E cleave SNAP-25 at different sites within the COOH-terminus, whereas B oNT-C also cleaves syntaxin. BoNTs are increasingly used in medicine for th e treatment of human diseases characterized by hyperfunction of cholinergic terminals. (C) 2000 Elsevier Science Ltd. All rights reserved.