MOLECULAR MECHANISMS OF TETANUS AND BOTUL INUM NEUROTOXINS

Tetanus (TeNT) and botulinum (BoNTs, seven serotypes A-G) neurotoxins are the causal agents of two severe diseases, tetanos and botulism. Te NT blocks preferentially GABA or glycine release in the central nervou s system whereas BoNTs inhibit acetylcholine release in periphery. The se neurotoxins are proteins constituted of a heavy and a light chains. The heavy chain mediates specific binding of toxins to neurone and tr anslocation of light chain into the cytoplasm. The light chain alone i s responsible for the intraneuronal blockade of neurotransmitter relea se. Recently, the light chain was found to be a zinc-endopeptidase. It attacks specifically synaptic proteins of the neuro-exocytotic appara tus. TeNT and BoNT/B, D, F and /G cleave VAMP/synaptobrevin an integra l protein of the synaptic vesicle membrane. BoNT/A and BoNT/E attack s pecifically SNAP-25, a protein associated to the plasma membrane. BoNT /C cleaves HPC1/syntaxin, an integral protein of tile plasma membrane that is associated to the calcium channels implicated in neurotransmit ter release.