Mechanism of action of tetanus and botulinum neurotoxins

@article{Montecucco1994MechanismOA,
  title={Mechanism of action of tetanus and botulinum neurotoxins},
  author={Cesare Montecucco and Glampietro Schiavo},
  journal={Molecular Microbiology},
  year={1994},
  volume={13}
}
The clostridial neurotoxins responsible for tetanus and botulism are metallo‐proteases that enter nerve cells and block neurotransmitter release via zinc‐dependent cleavage of protein components of the neuroexocytosis apparatus. Tetanus neurotoxin (TeNT) binds to the presynaptic membrane of the neuromuscular Junction and is internalized and transported retroaxonally to the spinal cord. Whilst TeNT causes spastic paralysis by acting on the spinal inhibitory interneurons, the seven serotypes of… 

Structure and function of tetanus and botulinum neurotoxins

Tetanus and botulinum neurotoxins form a new group of zinc-endopeptidases with characteristic sequence, mode of zinc coordination, mechanism of activation and target recognition, of great value in the unravelling of the mechanisms of exocytosis and endocytotic, as they are in the clinical treatment of dystonias.

Tetanus and Botulism Neurotoxins

The target specificity of these metallo-proteinases relies on a double recognition of their substrates based on interactions with the cleavage site and with a non contiguous segment that contains a structural motif common to VAMP, SNAP-25 and syntaxin.

The entry of tetanus and botulinum neurotoxins into neurons

This study found that the neurotoxin has to be bound to the membrane via at least two anchorage sites in order for a productive low-pH induced structural change to take place, and indicates auranofin, as a possible basis for the design of novel inhibitors of these neurotoxins.

Intracellular targets and metalloprotease activity of tetanus and botulism neurotoxins.

Tetanus and botulism neurotoxins (TeNT and BoNT, respectively) produced by Clostridia are the most toxic substances known: the mouse LD50 of highly purified preparations is between 0.1 and 1 ng/kg.

Growth of clostridia and preparation of their neurotoxins.

The mechanisms of action of botulinum and tetanus toxins are very similar; both are presynaptically acting neurotoxins which inhibit the calcium-mediated secretion of various neurotransmitter substances.

Endocytosis of Clostridium botulinum type B neurotoxin into rat brain synaptosomes.

In rat brain synaptosomes, type B neurotoxin was reduced presumably with sulfhydryls in the membrane and detected in the synaptic vesicle fraction which involved the degradation of VAMP-2 and the inhibition of neurotransmitter release, and the light chain in a free form was present in the cytosol fraction.

Substrate Recognition of VAMP-2 by Botulinum Neurotoxin B and Tetanus Neurotoxin*

Alanine-scanning mutagenesis and kinetic analysis identified three regions within VAMP-2 that were recognized by BoNT/B and TeNT: residues adjacent to the site of scissile bond cleavage (cleavage region) and residues located within N- terminal and C-terminal regions relative to the cleavage region.

Protease Activity of the Botulinum Neurotoxins

Understanding the mechanisms of BoNT action provides tools towards the development of strategies to identify novel small-molecule inhibitors of Bo NT catalysis and to extend the use of BoNNs as therapeutic agents.

Botulinum toxins in neurological disease

This review focuses on the pharmacology, electrophysiology, immunology, and application of botulinum toxin in selected neurological disorders, showing its ability to target peripheral cholinergic neurons without prominent central nervous system effects.
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The results indicate that tetanus and botulinum B neurotoxins block neurotransmitter release by cleaving synaptobrevin-2, a protein that, on the basis of the results, seems to play a key part in neurotransmitterRelease.

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