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Tetanus toxin entry. Nidogens are therapeutic targets for the prevention of tetanus.

Bercsenyi, K; Schmieg, N; Bryson, JB; Wallace, M; Caccin, P; Golding, M; Zanotti, G; ... Schiavo, G; + view all (2014) Tetanus toxin entry. Nidogens are therapeutic targets for the prevention of tetanus. Science , 346 (6213) 1118 - 1123. 10.1126/science.1258138. Green open access

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Abstract

Tetanus neurotoxin (TeNT) is among the most poisonous substances on Earth and a major cause of neonatal death in nonvaccinated areas. TeNT targets the neuromuscular junction (NMJ) with high affinity, yet the nature of the TeNT receptor complex remains unknown. Here, we show that the presence of nidogens (also known as entactins) at the NMJ is the main determinant for TeNT binding. Inhibition of the TeNT-nidogen interaction by using small nidogen-derived peptides or genetic ablation of nidogens prevented the binding of TeNT to neurons and protected mice from TeNT-induced spastic paralysis. Our findings demonstrate the direct involvement of an extracellular matrix protein as a receptor for TeNT at the NMJ, paving the way for the development of therapeutics for the prevention of tetanus by targeting this protein-protein interaction.

Type: Article
Title: Tetanus toxin entry. Nidogens are therapeutic targets for the prevention of tetanus.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/science.1258138
Publisher version: http://dx.doi.org/10.1126/science.1258138
Language: English
Additional information: FURTHER DISSEMINATION Authors are encouraged to further disseminate the accepted version of their manuscript, for release on the following schedule Six months following publication of the work by AAAS: To the funder’s designated repository
Keywords: Animals, Membrane Glycoproteins, Metalloendopeptidases, Mice, Mice, Inbred Strains, Motor Neurons, Neuromuscular Junction, Peptides, Protein Binding, Protein Interaction Domains and Motifs, Tetanus, Tetanus Toxin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1457200
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