CLOSTRIDIAL NEUROTOXINS

Abstract

Tetanus (TeNT) and botulinum (BoNTs) neurotoxins are powerful toxins endowed with a specific zinc-endopeptidase activity. Targets of these neurotoxins have been identified as synaptic members of the SNARE proteins, which are involved in the exocytosis of neurotransmitters at the synapse. Despite this identical intracellular mechanism of action, TeNT and BoNTs target different neurons in vivo. After binding at the neuromuscular junction, BoNTs block neurotransmitter release at this site, whereas TeNT is retrogradely transported through motor neurons and inhibits exocytosis in inhibitory interneurons. Recently, several studies have reported the structure of these neurotoxins and clarified important aspects of the intoxication process. However, important questions on the mechanism responsible for the binding specificity and for the targeting of TeNT and BoNTs remain to be addressed. Once elucidated, this novel information would enables us to use CNTs more efficiently as therapeutic tools in neuronal disorders.