title: Presynaptic enzymatic neurotoxins.
abstract: Botulinum neurotoxins produced by anaerobic bacteria of the genus Clostridium are the most toxic proteins known, with mouse LD50 values in the 1-5 ng/kg range, and are solely responsible for the pathophysiology of botulism. These metalloproteinases enter peripheral cholinergic nerve terminals and cleave proteins of the neuroexocytosis apparatus, causing a persistent, but reversible, inhibition of neurotransmitter release. They are used in the therapy of many human syndromes caused by hyperactive nerve terminals. Snake presynaptic PLA2 neurotoxins block nerve terminals by binding to the nerve membrane and catalyzing phospholipid hydrolysis with production of lysophospholipids and fatty acids. These compounds change the membrane conformation, causing enhanced fusion of synaptic vesicle via hemifusion intermediate with release of neurotransmitter and, at the same time, inhibition of vesicle fission and recycling. It is possible to envisage clinical applications of the lysophospholipid/fatty acid mixture to inhibit hyperactive superficial nerve terminals.
authors.affiliation: Dipartimento di Scienze Biomediche and Istituto CNR di Neuroscienze, Università di Padova, Padova, Italy. ornella.rossetto@unipd.it
authors.forename: Ornella
authors.initials: O
authors.lastname: Rossetto
authors.forename: Laura
authors.initials: L
authors.lastname: Morbiato
authors.forename: Paola
authors.initials: P
authors.lastname: Caccin
authors.forename: Michela
authors.initials: M
authors.lastname: Rigoni
authors.forename: Cesare
authors.initials: C
authors.lastname: Montecucco
mesh_terms: D000818:Animals; D001905:Botulinum Toxins / Q000502:physiology*; D006801:Humans; D009498:Neurotoxins / Q000633:toxicity*; D017729:Presynaptic Terminals / Q000201:enzymology*; D050600:SNARE Proteins / Q000378:metabolism* / Q000633:toxicity
chemical_list: D009498:Neurotoxins; D050600:SNARE Proteins; D001905:Botulinum Toxins