[Molecular mechanism of action of tetanus toxin and botulinum neurotoxins].

Tetanus toxin and botulinum neurotoxins are di-chain proteins of 150 kD molecular weight. They are produced by bacteria of the Clostridium genus. These toxins act on the nervous system by inhibiting neurotransmitter release (glycine and GABA in the case of tetanus toxin; acetylcholine in the case of botulinum neurotoxins) thus inducing the spastic or flaccid paralysis that characterizes tetanus and botulism, respectively. Their cellular mechanism of action involves three main steps, namely binding to the neurone membrane, internalization and intracellular blockade of the release mechanism for neurotransmitters. Membrane acceptors for these toxins are not yet fully identified; they would consist of membrane gangliosides and proteins. The internalization step would be achieved by endocytosis. Recent findings show that both binding and internalization are mediated only by the heavy chain of the toxins whereas the intracellular blockade of neurotransmitter release involves their light chain alone. The light chain has been identified as a zinc metalloprotease and its substrates would be proteins involved in the neurotransmitter release mechanism. The target of tetanus toxin and of botulinum neurotoxin type B is VAMP/synaptobrevin, a membrane protein of the synaptic vesicles of nerve cell terminals.