Abstract
Tetanus and botulinum neurotoxins are clostridial toxins that cause tetanus and botulism, respectively. Tetanus neurotoxin binds specifically to peripheral motoneuron nerve terminals at the neuromuscular junction and is endocytosed within vesicles, which transport the toxin retroaxonally to the spinal cord. Here, it enters the inhibitory interneurons that ensure the balanced contraction of opposing skeletal muscle, and the metalloprotease domain of the toxin inactivates VAMP/synaptobrevin, a protein essential for neurotransmitter release. The synapse of the inhibitory circuit at the spinal cord is blocked resulting in a characteristic spastic paralysis. The botulinum neurotoxins are produced in dozens of different isoforms that can be grouped into seven distinct serotypes. They bind to neurospecific receptors enriched in the presynaptic membrane of cholinergic nerve terminals and are then mainly internalized inside the synaptic vesicles wherefrom their metalloprotease domain translocates in the cytosol and cleaves one of the three SNARE proteins that form the core of the nanomachine which mediates the neuroexocytosis with ensuing flaccid paralysis. In spite of the opposing clinical symptoms, botulinum and tetanus neurotoxins intoxicate neuronal cells in the same way and have similar functional and structural organizations. Common features and molecular diversities between tetanus and botulinum neurotoxin mechanism of action will be discussed in this present chapter.
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Work in the authors’ laboratory is supported by the University of Padova, Fondazione Cariparo, and the Italian Ministry of Defence.
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Rossetto, O., Montecucco, C. (2016). Tetanus and Botulinum Neurotoxins. In: Gopalakrishnakone, P., Stiles, B., Alape-Girón, A., Dubreuil, J., Mandal, M. (eds) Microbial Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6725-6_19-1
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