76051 20220208112845.0 doi 10.1007/s12035-017-0832-8 sideral 103787 ART-2017-103787 eng Otero García, Alicia Universidad de Zaragoza (orcid)0000-0001-9075-2764 An amino acid substitution found in animals with low susceptibility to prion diseases confers a protective dominant-negative effect in prion-infected transgenic mice 2017 Access copy available to the general public Unrestricted While prion diseases have been described in numerous species, some, including those of the Canidae family, appear to show resistance or reduced susceptibility. A better understanding of the factors underlying prion susceptibility is crucial for the development of effective treatment and control measures. We recently demonstrated resistance to prion infection in mice overexpressing a mutated prion protein (PrP) carrying a specific amino acid substitution characteristic of canids. Here, we show that coexpression of this mutated PrP and wild-type mouse PrP in transgenic mice inoculated with different mouse-adapted prion strains (22 L, ME7, RML, and 301C) significantly increases survival times (by 45 to 113%). These data indicate that this amino acid substitution confers a dominant-negative effect on PrP, attenuating the conversion of PrPC to PrPSc and delaying disease onset without altering the neuropathological properties of the prion strains. Taken together, these findings have important implications for the development of new treatment approaches for prion diseases based on dominant-negative proteins. info:eu-repo/grantAgreement/ES/DGA/C020-2014 info:eu-repo/grantAgreement/ES/MINECO/AGL2015-65046-C2-1-R info:eu-repo/grantAgreement/ES/MINECO/AGL2015-65560-R info:eu-repo/grantAgreement/ES/MINECO/PCIN-2013-065 info:eu-repo/grantAgreement/ES/MINECO/SEV-2016-0644 info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 5.076 2017 NEUROSCIENCES 44 / 261 = 0.169 2017 Q1 T1 1.614 2017 Neurology 2017 Q1 Neuroscience (miscellaneous) 2017 Q1 Cellular and Molecular Neuroscience 2017 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Bolea Bailo, Rosa Universidad de Zaragoza (orcid)0000-0002-2746-3932 Hedman Altamirano, Carlos (orcid)0000-0002-0827-110X Fernández-Borges, Natalia Marín González, María Belén Universidad de Zaragoza (orcid)0000-0002-1590-3347 López Pérez, Óscar Universidad de Zaragoza (orcid)0000-0003-2454-2114 Barrio Alegre, Tomás Universidad de Zaragoza (orcid)0000-0002-7037-6316 Eraña, Hasier Sánchez-Martín, Manuel A. Monzón Garcés, Marta Universidad de Zaragoza (orcid)0000-0002-2787-9671 Badiola Díez, Juan José Universidad de Zaragoza (orcid)0000-0002-7173-7216 Castilla, Joaquín 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 55, 7 (2017), 6182-6192 Mol. neurobiol. MOLECULAR NEUROBIOLOGY 0893-7648 1966143 http://zaguan.unizar.es/record/76051/files/texto_completo.pdf Postprint 63878 http://zaguan.unizar.es/record/76051/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:76051 articulos driver 2022-02-08-11:23:42 ARTICLE