[Botulinum neurotoxin].
Botulinum toxin is a multi-molecular complex comprised of a neuro-active moiety (i.e. botulinum neurotoxin) and several associated non-toxic proteins. The toxin dissociates rapidly at plasmatic pH, thereby releasing neurotoxin. Nerve terminals only take up the neurotoxin. In the peripheral nerve system, the neurotoxin mainly blocks acetylcholine release. When acting at the neuromuscular junctions, this results in paralysis of the muscle fibers. The duration of the neurotoxin action is mainly determined by the life-time of neurotoxin molecules inside the nerve terminals. Inhibition of cholinergic transmission induces rapid atrophy of the muscle fibres, and, sometimes, sprouting from poisoned nerve terminals. These effects, as well as the acetylcholine release blockade are entirely reversible. When injected in the periphery, a direct action of botulinum neurotoxin in the central nervous system remains unlikely despite its retrograde ascent demonstrated in animal models. However, indirect effects are numerous. The constituting proteins of the toxin complex can lead to immunisation against the non-toxic associated proteins and neurotoxin. Only the antibodies directed against neurotoxin are potentially neutralizing.
UPR3212, CNRS, institut des neurosciences cellulaires et intégratives, université de Strasbourg, 5, rue Blaise-Pascal, 67084 Strasbourg cedex, France. poulain@neurochem.u-strasbg.fr
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Poulain
D000818:Animals; D001905:Botulinum Toxins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity; D002490:Central Nervous System / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007114:Immunization; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity; D010447:Peptide Hydrolases / Q000737:chemistry; D017933:Peripheral Nervous System / Q000187:drug effects; D021381:Protein Transport; D009435:Synaptic Transmission / Q000187:drug effects
D009498:Neurotoxins; D010447:Peptide Hydrolases; D001905:Botulinum Toxins