106738 20230519145440.0 doi 10.1007/s12035-021-02489-5 sideral 124702 ART-2021-124702 eng Betancor, M. Universidad de Zaragoza (orcid)0000-0002-0388-9429 Therapeutic assay with the non-toxic c-terminal fragment of tetanus toxin (TTC) in transgenic murine models of prion disease 2021 Access copy available to the general public Unrestricted 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. info:eu-repo/grantAgreement/ES/DGA/A19-20R info:eu-repo/grantAgreement/EUR/FEDER/INTERREG-V-A-POCTEFA-2014-2020 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.686 2021 NEUROSCIENCES 69 / 275 = 0.251 2021 Q2 T1 1.271 2021 Neurology 2021 Q1 Cellular and Molecular Neuroscience 2021 Q1 11.0 2021 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Moreno Martínez, L. Universidad de Zaragoza (orcid)0000-0002-7277-4318 López-Pérez, Ó. (orcid)0000-0003-2454-2114 Otero, A. Universidad de Zaragoza (orcid)0000-0001-9075-2764 Hernaiz, A. Universidad de Zaragoza (orcid)0000-0002-6806-9990 Barrio, T. Badiola, J.J. Universidad de Zaragoza (orcid)0000-0002-7173-7216 Osta, R. Universidad de Zaragoza (orcid)0000-0001-5687-6704 Bolea, R. Universidad de Zaragoza (orcid)0000-0002-2746-3932 Martín Burriel, I. Universidad de Zaragoza (orcid)0000-0001-6016-4726 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 1012 315 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Farmacología 58 (2021), 5312–5326 Mol. neurobiol. MOLECULAR NEUROBIOLOGY 0893-7648 21349733 http://zaguan.unizar.es/record/106738/files/texto_completo.pdf Versión publicada 2408577 http://zaguan.unizar.es/record/106738/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:106738 articulos driver 2023-05-18-14:29:56 ARTICLE