Nidogens are therapeutic targets for the prevention of tetanus

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 nido...

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Published in:Science (American Association for the Advancement of Science) 2014-11, Vol.346 (6213), p.1118-1123
Main Authors: Bercsenyi, Kinga, Schmieg, Nathalie, Bryson, J. Barney, Wallace, Martin, Caccin, Paola, Golding, Matthew, Zanotti, Giuseppe, Greensmith, Linda, Nischt, Roswitha, Schiavo, Giampietro
Format: Article
Language:English
Subjects:
Anatomy
Antibodies
Bacteria
Binding
Clostridium botulinum
Mice
Motor neurons
Muscles
Neurons
Neurotoxicity
Peptides
Proteins
Receptors
Research facilities
T lymphocytes
Tetanus
Toxins
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1258138