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

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.