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Botulinum Neurotoxins: Mechanism of Action

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Botulinum Toxin Therapy

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 263))

Abstract

Botulinum neurotoxins (BoNTs) are a growing family of bacterial protein toxins that cause botulism, a rare but often fatal animal and human disease. They are the most potent toxins known owing to their molecular architecture, which underlies their mechanism of action. BoNTs target peripheral nerve terminals by a unique mode of binding and enter into their cytosol where they cleave SNARE proteins, thus inhibiting the neurotransmitter release. The specificity and rapidity of binding, which limits the anatomical area of its neuroparalytic action, and its reversible action make BoNT a valuable pharmaceutical to treat neurological and non-neurological diseases determined by hyperactivity of cholinergic nerve terminals. This review reports the progress on our understanding of how BoNTs cause nerve paralysis highlighting the different steps of their molecular mechanism of action as key aspects to explain their extreme toxicity but also their unique pharmacological properties.

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Acknowledgements

Work in the author’s laboratory is supported by University of Padova, CNR and the Ministry of Defence research project RI.PA.NE.

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Padova, Padova, Italy

    O. Rossetto, M. Pirazzini, F. Fabris & C. Montecucco

  2. Institute of Neuroscience, National Research Council, Padova, Italy

    C. Montecucco

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  1. O. Rossetto
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  2. M. Pirazzini
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  3. F. Fabris
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  4. C. Montecucco
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Editors and Affiliations

  1. Akrivista and Whitecap Biosciences, Irvine, CA, USA

    Scott M. Whitcup

  2. Bethesda, MD, USA

    Mark Hallett

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Rossetto, O., Pirazzini, M., Fabris, F., Montecucco, C. (2020). Botulinum Neurotoxins: Mechanism of Action. In: Whitcup, S.M., Hallett, M. (eds) Botulinum Toxin Therapy. Handbook of Experimental Pharmacology, vol 263. Springer, Cham. https://doi.org/10.1007/164_2020_355

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