Clostridial Neurotoxins The Molecular Pathogenesis of Tetanus and Bo
Tetanus has been known from the very beginning of medical literature since it was first described by Hyppocrates of Cos in the fifth century B.C. For 24 centuries it was considered a neuro logical disease until the breakthrough of CARLE and RATIONE (1884
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Editors
A. Capron, Lille . R.W. Compans, Atlanta/Georgia M. Cooper, Birmingham/Alabama· H. Koprowski, Philadelphia· I. McConnell, Edinburgh· F. Melchers, Basel M. Oldstone, La Jolla/California· S. Olsnes, Oslo M. Potter, Bethesda/Maryland· H. Saedler, Cologne P.K. Vogt, La Jolla/California· H. Wagner, Munich I. Wilson, La Jolla/California
Springer Berlin Heidelberg New York Barcelona Budapest Hong Kong London Milan Paris Tokyo
Clostridial Neurotoxins The Molecular Pathogenesis of Tetanus and Botulism
Edited by C. Montecucco
With 28 Figures
,
Springer
CESARE MONTECUCCO
Universita degli Studi di Padova Dipartimento di Scienze Biomediche Sperimentali Via Trieste, 75 35121 Padova Italia
Cover illustration: Tetanus and botulinum neurotoxins intoxication of nerve cells. These toxins bind to the presynaptic membrane (step 1) and are internalized by endocytosis (step 2). The lumen of the synaptic vesicle becomes acidic following the operation of a vacuolar-type A TPase proton pump. This induces a structural transition of the toxin which becomes able to insert in the vesicle membrane and to translocate the L chain (red) in the cytosol (step 3). Inside the neuron cytosol, L blocks neuroexocytosis via selective zincdependent proteolysis of a protein component of the neuroexocytosis apparatus (step 4). Tetanus neurotoxin and botulinum neurotoxins B, 0, F and G cleave specifically VAMP (violet), while types A and E cleave SNAP-25 (yellow) and botulinum neurotoxin type C cleaves syntaxin (green). Cover design: Kunkel+Lopka, IIvesheim ISBN-13: 978-3-642-85175-9 001 10.1007/978-3-642-85173-5
e-ISBN-13: 978-3-642-85173-5
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Preface
Tetanus has been known from the very beginning of medi
