Molecular mechanism of action of botulinal neurotoxins and the synaptic remodeling they induce in vivo at the skeletal neuromuscular junction - Archive ouverte HAL Accéder directement au contenu
Chapitre D'ouvrage Année : 2001

Molecular mechanism of action of botulinal neurotoxins and the synaptic remodeling they induce in vivo at the skeletal neuromuscular junction

Résumé

Botulinal neurotoxins (BoNTs) have long been known to have potent and specific paralytic effects at the vertebrate neuromuscular junction (NMJ). Although they are the most toxic substances known, the serotype A is now being used for therapeutic purposes, mainly to treat involuntary muscle contractions, but also for a number of other medical applications. During the last decade, the most significant milestone discoveries have paved the way in this field starting with the discovery of their metalloprotease activity targeting key components of the exocytotic machinery, and they culminated with the elucidation of the crystal structure of BoNT/A and /B (3-5). BoNTs, when injected in the vicinity of a muscle, reach the motor-nerve terminal cytosol by a sequence of several steps. The toxins' metalloproteolytic activity blocks acetylcholine (ACh) release and produces a profound but transient skeletalmuscle paralysis in vivo. In addition, BoNTs trigger a pronounced outgrowth along intramuscular axons and nerve terminals and a remodeling of the NMJ, which contributes to the eventual functional recovery of neuromuscular transmission. These phenomena provide an excellent model for analyzing the cellular and molecular interactions involved in the plasticity of synaptic contacts.
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Dates et versions

hal-00194091 , version 1 (05-12-2007)

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Frédéric A. Meunier, Judit Herreros, Giampietro Schiavo, Bernard Poulain, Jordi Molgó. Molecular mechanism of action of botulinal neurotoxins and the synaptic remodeling they induce in vivo at the skeletal neuromuscular junction. Edward J. Massaro. Handbook of Neurotoxicology, Humana Press Totowa, NJ, USA, pp.305-347, 2001, ISBN: 0-89603-795-9, ⟨10.1226/0896037959⟩. ⟨hal-00194091⟩

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