Identification of the major steps in botulinum toxin action

被引:386
作者
Simpson, LL [1 ]
机构
[1] Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA
[2] Jefferson Med Coll, Dept Biochem, Philadelphia, PA 19107 USA
[3] Jefferson Med Coll, Dept Mol Pharmacol, Philadelphia, PA 19107 USA
关键词
acetylcholine; airway epithelia; gut epithelia; endoprotease; neuroinuscular junction;
D O I
10.1146/annurev.pharmtox.44.101802.121554
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Botulinum toxin is a uniquely potent substance synthesized by the organisms Clostridium botulinum, Clostridium baratii, and Clostridium butyricum. This toxin, which acts preferentially on peripheral cholinergic nerve endings to block acetylcholine release, is both an agent that causes disease (i.e., botulism) as well as an agent that can be used to treat disease (e.g., dystonia). The ability of botulinum. toxin to produce its effects is largely dependent on its ability to penetrate cellular and intracellular membranes. Thus, toxin that is ingested or inhaled can bind to epithelial cells and be transported to the general circulation. Toxin that reaches peripheral nerve endings binds to the cell surface then penetrates the plasma membrane by receptor-mediated endocytosis and the endosome membrane by pH-induced translocation. Internalized toxin acts in the cytosol as a metalloendoprotease to cleave polypeptides that are essential for exocytosis. This review seeks to identify and characterize all major steps in toxin action, from initial absorption to eventual paralysis of cholinergic transmission.
引用
收藏
页码:167 / 193
页数:31
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