Therapeutic Assay with the Non-toxic C-Terminal Fragment of Tetanus Toxin (TTC) in Transgenic Murine Models of Prion Disease

Autor: Inmaculada Martín-Burriel, Óscar López-Pérez, Juan José Badiola, Marina Betancor, Alicia Otero, Laura Moreno-Martínez, Rosa Bolea, Rosario Osta, Adelaida Hernaiz, Tomás Barrio
Přispěvatelé: University of Zaragoza - Universidad de Zaragoza [Zaragoza], Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Instituto de Investigación Sanitaria de Aragón [Zaragoza] (IIS Aragón), Instituto Agroalimentario de Aragón (IA2), University of Zaragoza - Universidad de Zaragoza [Zaragoza]-Centro de Investigación y Tecnología Agroalimentaria de Aragón (CITA), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Open Access funding provided thanks to the CRUE‐CSIC agreement with Springer Nature. The project has been 65% cofinanced by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra programme (POCTEFA 2014–2020). POCTEFA aims to reinforce the economic and social integration of the French–Spanish–Andorran border. Its support is focused on developing economic, social and environmental cross-border activities through joint strategies favouring sustainable territorial development., European Project: ERDF, European Project: EFA282/13, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Molecular Neurobiology
Zaguán. Repositorio Digital de la Universidad de Zaragoza
instname
Molecular Neurobiology, 2021, 58 (10), pp.5312-5326. ⟨10.1007/s12035-021-02489-5⟩
Molecular Neurobiology, Humana Press, 2021, 58 (10), pp.5312-5326. ⟨10.1007/s12035-021-02489-5⟩
Dipòsit Digital de la UB
Universidad de Barcelona
ISSN: 1559-1182
0893-7648
DOI: 10.1007/s12035-021-02489-5⟩
Popis: The non-toxic C-terminal fragment of the tetanus toxin (TTC) has been described as a neuroprotective molecule since it binds to Trk receptors and activates Trk-dependent signaling, activating neuronal survival pathways and inhibiting apoptosis. Previous in vivo studies have demonstrated the ability of this molecule to increase mice survival, inhibit apoptosis and regulate autophagy in murine models of neurodegenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Prion diseases are fatal neurodegenerative disorders in which the main pathogenic event is the conversion of the cellular prion protein (PrPC) into an abnormal and misfolded isoform known as PrPSc. These diseases share different pathological features with other neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson’s disease or Alzheimer’s disease. Hitherto, there are no effective therapies to treat prion diseases. Here, we present a pilot study to test the therapeutic potential of TTC to treat prion diseases. C57BL6 wild-type mice and the transgenic mice Tg338, which overexpress PrPC, were intracerebrally inoculated with scrapie prions and then subjected to a treatment consisting of repeated intramuscular injections of TTC. Our results indicate that TTC displays neuroprotective effects in the murine models of prion disease reducing apoptosis, regulating autophagy and therefore increasing neuronal survival, although TTC did not increase survival time in these models.
Databáze: OpenAIRE
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