Mechanism of action of tetanus and botulinum neurotoxins

Mol Microbiol. 1994 Jul;13(1):1-8. doi: 10.1111/j.1365-2958.1994.tb00396.x.

Abstract

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 botulinum neurotoxins (BoNT) induce a flaccid paralysis because they intoxicate the neuromuscular junction. TeNT and BoNT serotypes B, D, F and G specifically cleave VAMP/synaptobrevin, a membrane protein of small synaptic vesicles, at different single peptide bonds. Proteins of the presynaptic membrane are specifically attacked by the other BoNTs: serotypes A and E cleave SNAP-25 at two different sites located within the carboxyl terminus, whereas the specific target of serotype C is syntaxin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Botulinum Toxins / chemistry
  • Botulinum Toxins / pharmacology*
  • Catalysis
  • Endocytosis
  • Exocytosis / drug effects
  • Ion Channels / metabolism
  • Metalloendopeptidases / pharmacology
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / drug effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurotoxins / chemistry
  • Neurotoxins / pharmacology*
  • Protein Binding
  • Protein Conformation
  • Structure-Activity Relationship
  • Tetanus Toxin / chemistry
  • Tetanus Toxin / pharmacology
  • Zinc / physiology

Substances

  • Ion Channels
  • Nerve Tissue Proteins
  • Neurotoxins
  • Tetanus Toxin
  • Metalloendopeptidases
  • zinc-endopeptidase, tetanus neurotoxin
  • Botulinum Toxins
  • Zinc

Grant support