title: Synaptic transmission: inhibition of neurotransmitter release by botulinum toxins.
abstract: Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation. At the neuromuscular junction, the presynaptic nerve ending is packed with synaptic vesicles filled with acetylcholine, and clustered at the tip of the folds of the postsynaptic muscle membrane are the acetylcholine receptors. Synaptic vesicles fuse with the membrane in response to an elevation of intraneuronal calcium concentration and undergo release of their transmitter by exocytosis. Intracellular proteins that contribute to the fusion of the vesicles with the plasma membrane during exocytosis include synaptosomal protein with a molecular weight of 25 kDa (SNAP-25); vesicle-associated membrane protein (VAMP), also known as synaptobrevin; and syntaxin. Through their proteolytic action on these proteins, botulinum toxins prevent exocytosis, thereby inhibiting the release of acetylcholine. There are 7 serotypes of this toxin-A, B, C1, D, E, F, and G-and each cleaves a different intracellular protein or the same target at distinct bonds. The separate cleavage sites in SNAP-25 for botulinum toxin types A and E contribute to their dissimilar durations of muscle relaxation. This report describes the molecular basis for the inhibition by botulinum toxins of neuroexocytosis and subsequent functional recovery at the neuromuscular junction.
authors.affiliation: Centre for Neurobiochemistry, Department of Biological Sciences, Imperial College, London, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Dolly
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
chemical_list: D001905:Botulinum Toxins; D000109:Acetylcholine