Title: How do the Botulinum Neurotoxins block neurotransmitter release: from botulism to the molecular mechanism of action

Authors: Bernard Poulain, Michel R. Popoff, Jordi Molgo

Addresses: Institut des Neurosciences Cellulaires et Integratives, UMR 7168 CNRS et Universite de Strasbourg, 5 rue Blaise Pascal, F-67084 Strasbourg cedex, France. ' Unite des Bacteries anaerobies et Toxines, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France. ' CNRS, Institut de Neurobiologie Alfred Fessard – FRC2118, Laboratoire de Neurobiologie Cellulaire et Moleculaire – UPR9040, Gif sur Yvette, F-91198, France

Abstract: An overall picture of the botulinum toxins is provided, linking the recent developments in their molecular and cellular aspects to the physiological actions. The pathophysiological aspects of botulinum poisoning (clinical symptoms and physical findings, synaptic effects at the motor and non-motor nerve terminals) and indirect consequences (muscle atrophy, transient formation of new end-plates) are described. The role of the botulinum toxin complex constituents in dissemination, selective binding of the neurotoxins to nerve terminals and intestinal epithelial cells, endocytosis, intracellular trafficking, translocation into the cytosol, and proteolytic attack of the neurotransmitter release machinery are analysed in a molecular and cellular perspective. [Received 23 October 2007; Accepted 12 December 2007]

Keywords: botulinum neurotoxins; toxin complex; hemagglutinin; dissemination; receptors; intracellular traffic; metalloprotease; SNARE; paralysis duration; muscle changes; neurotransmitter release; botulism; molecular mechanisms; pathophysiology; botulinum poisoning.

DOI: 10.1504/TBJ.2008.018951

The Botulinum Journal, 2008 Vol.1 No.1, pp.14 - 87

Published online: 25 Jun 2008 *

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