Neurotrophic properties of C-terminal domain of the heavy chain of tetanus toxin on motor neuron diseases

The carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) exerts a neuroprotective effect in neurodegenerative diseases via the activation of signaling pathways related to neurotrophins, and also through inhibiting apoptotic cell death. Here, we demonstrate that Hc-TeTx preserves mo...

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Detalles Bibliográficos
Autores: Herrando-Grabulosa, Mireia|||0000-0002-6685-3220, Aguilera, José|||0000-0002-9906-8034, Casas Louzao, Caty|||0000-0002-2273-6321, Talbot, Kevin|||0000-0001-5490-1697
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:233807
Acceso en línea:https://ddd.uab.cat/record/233807
https://dx.doi.org/urn:doi:10.3390/toxins12100666
Access Level:acceso abierto
Palabra clave:Carboxyl-terminal domain of the heavy chain of tetanus toxin
Neuroprotection
Excitotoxicity
Spinal muscular atrophy
Amyotrophic lateral sclerosis
Descripción
Sumario:The carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) exerts a neuroprotective effect in neurodegenerative diseases via the activation of signaling pathways related to neurotrophins, and also through inhibiting apoptotic cell death. Here, we demonstrate that Hc-TeTx preserves motoneurons from chronic excitotoxicity in an in vitro model of amyotrophic lateral sclerosis. Furthermore, we found that PI3-K/Akt pathway, but not p21ras/MAPK pathway, is involved in their beneficial effects under chronic excitotoxicity. Moreover, we corroborate the capacity of the Hc-TeTx to be transported retrogradely into the spinal motor neurons and also its capacity to bind to the motoneuron-like cell line NSC-34. These findings suggest a possible therapeutic tool to improve motoneuron preservation in neurodegenerative diseases such as amyotrophic lateral sclerosis.