title: Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction.
abstract: Botulinum neurotoxins (BoNTs) and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ) blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body.
authors.affiliation: Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy. elisa.duregotti@gmail.com.
authors.forename: Elisa
authors.initials: E
authors.lastname: Duregotti
authors.affiliation: Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy. gzanetti89@gmail.com.
authors.forename: Giulia
authors.initials: G
authors.lastname: Zanetti
authors.affiliation: Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy. scorzeto.michele@gmail.com.
authors.forename: Michele
authors.initials: M
authors.lastname: Scorzeto
authors.affiliation: Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy. aram.megighian@unipd.it.
authors.forename: Aram
authors.initials: A
authors.lastname: Megighian
authors.affiliation: Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy. cesare.montecucco@gmail.com.|Institute for Neuroscience, National Research Council, Via U. Bassi 58/B, 35131 Padova, Italy. cesare.montecucco@gmail.com.
authors.forename: Cesare
authors.initials: C
authors.lastname: Montecucco
authors.affiliation: Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy. marcopiraz@gmail.com.
authors.forename: Marco
authors.initials: M
authors.lastname: Pirazzini
authors.affiliation: Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy. rigonimic@gmail.com.
authors.forename: Michela
authors.initials: M
authors.lastname: Rigoni
mesh_terms: D000818:Animals; D001905:Botulinum Toxins / Q000633:toxicity*; D002038:Bungarotoxins / Q000633:toxicity*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D012911:Snakes; D013111:Spider Venoms / Q000633:toxicity*; D013112:Spiders; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D050987:Vesicle-Associated Membrane Protein 1 / Q000378:metabolism
chemical_list: D002038:Bungarotoxins; D009498:Neurotoxins; C494209:Snap25 protein, mouse; D013111:Spider Venoms; D050825:Synaptosomal-Associated Protein 25; D050987:Vesicle-Associated Membrane Protein 1; C494771:vesicle-associated membrane protein 1, mouse; C020763:alpha-latrotoxin; D001905:Botulinum Toxins
keywords: DAS assay; animal neurotoxins; botulinum neurotoxins; mouse; nerve terminals degeneration; neuroexocytosis; paralysis