title: Redox regulation of botulinum neurotoxin toxicity: therapeutic implications.
abstract: Botulinum neurotoxin causes botulism, and the only effective antidote is the antitoxin. Botulinum neurotoxins are disulfide linked di-chain proteins encompassing a light chain Zn2+-protease that is translocated by a heavy chain channel from the synaptic vesicle lumen into the neuronal cytosol where it acts. Protease release from the channel is required for toxicity. The Thioredoxin Reductase-Thioredoxin system cleaves the interchain disulfide, and its inhibition prevents neurotoxicity, and may provide novel strategies for chemoprophylaxis and therapy.
authors.affiliation: Section of Neurobiology, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: mmontal@ucsd.edu.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Montal
mesh_terms: D001905:Botulinum Toxins / Q000378:metabolism* / Q000633:toxicity*; D001906:Botulism / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D010084:Oxidation-Reduction; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase; D001905:Botulinum Toxins
keywords: SNAREs; botulism; channel; chaperone; protease; thioredoxin