Thioredoxin and Its Reductase Are Present on Synaptic Vesicles, and Their Inhibition Prevents the Paralysis Induced by Botulinum Neurotoxins (Articolo in rivista)

Type
Label
  • Thioredoxin and Its Reductase Are Present on Synaptic Vesicles, and Their Inhibition Prevents the Paralysis Induced by Botulinum Neurotoxins (Articolo in rivista) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.celrep.2014.08.017 (literal)
Alternative label
  • Pirazzini, Marco; Tehran, Domenico Azarnia; Zanetti, Giulia; Megighian, Aram; Scorzeto, Michele; Fillo, Silvia; Shone, Clifford C.; Binz, Thomas; Rossetto, Ornella; Lista, Florigio; Montecucco, Cesare (2014)
    Thioredoxin and Its Reductase Are Present on Synaptic Vesicles, and Their Inhibition Prevents the Paralysis Induced by Botulinum Neurotoxins
    in Cell reports
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Pirazzini, Marco; Tehran, Domenico Azarnia; Zanetti, Giulia; Megighian, Aram; Scorzeto, Michele; Fillo, Silvia; Shone, Clifford C.; Binz, Thomas; Rossetto, Ornella; Lista, Florigio; Montecucco, Cesare (literal)
Pagina inizio
  • 1870 (literal)
Pagina fine
  • 1878 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://www.ncbi.nlm.nih.gov/pubmed/25220457 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 8 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 9 (literal)
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  • 6 (literal)
Note
  • Scopu (literal)
  • ISI Web of Science (WoS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1, 5, 9, 11: Department of Biomedical Sciences and National Research Council Institute of Neuroscience, University of Padova, Via Ugo Bassi 58/B, 35121 Padova, Italy; 6, 10: Histology and Molecular Biology Section, Army Medical and Veterinary Research Center, Via Santo Stefano Rotondo 4, 00184 Rome, Italy; 7: Public Health England, Porton Down, Salisbury, Wiltshire SP4 OJG, UK; 8: Institut fur Biochemie, Medizinische Hochschule Hannover, 30623 Hannover, Germany (literal)
Titolo
  • Thioredoxin and Its Reductase Are Present on Synaptic Vesicles, and Their Inhibition Prevents the Paralysis Induced by Botulinum Neurotoxins (literal)
Abstract
  • Botulinum neurotoxins consist of a metalloprotease linked via a conserved interchain disulfide bond to a heavy chain responsible for neurospecific binding and translocation of the enzymatic domain in the nerve terminal cytosol. The metalloprotease activity is enabled upon disulfide reduction and causes neuroparalysis by cleaving the SNARE proteins. Here, we show that the thioredoxin reductase-thioredoxin protein disulfide-reducing system is present on synaptic vesicles and that it is functional and responsible for the reduction of the interchain disulfide of botulinum neurotoxin serotypes A, C, and E. Specific inhibitors of thioredoxin reductase or thioredoxin prevent intoxication of cultured neurons in a dose-dependent manner and are also very effective inhibitors of the paralysis of the neuromuscular junction. We found that this group of inhibitors of botulinum neurotoxins is very effective in vivo. Most of them are nontoxic and are good candidates as preventive and therapeutic drugs for human botulism. (literal)
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