The blockade of the neurotransmitter release apparatus by botulinum neurotoxins

摘要: The high toxicity of the seven serotypes botulinum neurotoxins (BoNT/A to G), together with their specificity and reversibility, includes them in list A potential bioterrorism weapons and, at same time, among therapeutics choice for a variety human syndromes. They invade nerve terminals cleave specifically three proteins which form heterotrimeric SNAP REceptors (SNARE) complex that mediates neurotransmitter release. BoNT-induced cleavage SNARE explains by itself paralysing activity BoNTs because truncated cannot complex. However, case BoNT/A, most widely used toxin therapy, additional factors come into play as it only removes few residues from synaptosomal associate protein 25 kDa C-terminus this results long duration action. To explain these facts other experimental data, we present here model assembly neuroexocytosis apparatus Synaptotagmin Complexin first assist zippering complex, then stabilize clamp an octameric radial complexes.