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Tetanus, botulinum and snake presynaptic neurotoxins

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Abstract

Tetanus and botulinum neurotoxins, produced by anaerobic bacteria of the genus Clostridium, are the most toxic proteins known and are solely responsible for the pathogenesis of tetanus and botulism. They are metallo-proteases that enter nerve terminals and cleave proteins of the neuroexocytosis apparatus causing a persistent, but reversible, inhibition of neurotransmitter release. Botulinum neurotoxins are used in the therapy of many human syndromes caused by hyperactive nerve terminals. Snake presynaptic PLA2 neurotoxins block nerve terminals by binding to the nerve membrane and catalyzing phospholipid hydrolysis with production of lysophospholipids and fatty acids. These compounds change the membrane conformation causing enhanced fusion of synaptic vesicle via hemifusion intermediate with release of neurotransmitter and, at the same time, inhibition of vesicle fission and recycling. It is possible to envisage clinical applications of the lysophospholipid/fatty acid mixture to inhibit hyperactive superficial nerve terminals.

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Abbreviations

ACh:

acetylcholine

BoNT:

botulinum neurotoxin

FA:

fatty acid

LPL:

lysophospholipid

NMJ:

neuromuscular junction

SNAP-25:

25-kDa synaptosomal-associated protein

SNARE:

soluble N-ethylmaleimide-sensitive factor attachment protein receptor

VAMP:

vesicle-associated membrane protein

SPAN:

snake presynaptic PLA2 neurotoxin

SV:

synaptic vesicles

TeNT:

tetanus neurotoxin

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Authors and Affiliations

  1. Dipartimento di Scienze Biomediche and Istituto CNR di Neuroscienze, Università di Padova, Via G. Colombo 3, 35121, Padova, Italy

    Ornella Rossetto, Laura Morbiato, Paola Caccin, Michela Rigoni, Luca Carli, Marco Paoli, Mariana Cintra-Francischelli & Cesare Montecucco

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  1. Ornella Rossetto
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  2. Laura Morbiato
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  3. Paola Caccin
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  4. Michela Rigoni
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  8. Cesare Montecucco
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Correspondence to Cesare Montecucco.

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Rossetto, O., Morbiato, L., Caccin, P. et al. Tetanus, botulinum and snake presynaptic neurotoxins. Rend. Fis. Acc. Lincei 19, 173–188 (2008). https://doi.org/10.1007/s12210-008-0010-z

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