Botulinum Neurotoxins: Structure and Mechanism of Action
Roshan Kukreja and Bal Ram Singh
from: Microbial Toxins: Current Research and Future Trends (Edited by: Thomas Proft). Caister Academic Press, U.K. (2009)
Abstract
Botulinum neurotoxins (BoNTs) are the most potent natural toxins known to humankind. The family of BoNTs comprises of seven antigenically distinct serotypes (A to G) that are produced by various toxigenic strains of spore-forming anaerobic Clostridium botulinum. They act as metalloproteinases that enter peripheral cholinergic nerve terminals and cleave proteins that are crucial components of the neuroexocytosis apparatus, causing a persistent but reversible inhibition of neurotransmitter release resulting in flaccid muscle paralysis.
Apart from being the sole causative agent of the deadly food poisoning disease, botulism, BoNTs pose a major biological warfare threat due to their extreme toxicity and easy production. Interestingly they also serve as powerful tools to treat an ever expanding list of medical conditions. A better understanding of the structure-function relationship of clostridial neurotoxins will not only help decipher their molecular mode of action but will also provide a greater understanding of the potential use of their individual domains in answering more fundamental questions of neuroexocytosis. It is also critical for designing effective specific inhibitors to counter botulism biothreat, and for the development of new therapeutics read more ...
