An amino acid substitution found in animals with low susceptibility to prion diseases confers a protective dominant-negative effect in prion-infected transgenic mice

Otero García, Alicia (Universidad de Zaragoza) ; Bolea Bailo, Rosa (Universidad de Zaragoza) ; Hedman Altamirano, Carlos ; Fernández-Borges, Natalia ; Marín González, María Belén (Universidad de Zaragoza) ; López Pérez, Óscar (Universidad de Zaragoza) ; Barrio Alegre, Tomás (Universidad de Zaragoza) ; Eraña, Hasier ; Sánchez-Martín, Manuel A. ; Monzón Garcés, Marta (Universidad de Zaragoza) ; Badiola Díez, Juan José (Universidad de Zaragoza) ; Castilla, Joaquín

Resumen: 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.

Idioma: Inglés

DOI: 10.1007/s12035-017-0832-8

Año: 2017

Publicado en: MOLECULAR NEUROBIOLOGY 55, 7 (2017), 6182-6192
ISSN: 0893-7648

Factor impacto JCR: 5.076 (2017)

Categ. JCR: NEUROSCIENCES rank: 44 / 261 = 0.169 (2017) - Q1 - T1

Factor impacto SCIMAGO: 1.614 - Neurology (Q1) - Neuroscience (miscellaneous) (Q1) - Cellular and Molecular Neuroscience (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA/C020-2014
Financiación: info:eu-repo/grantAgreement/ES/MINECO/AGL2015-65046-C2-1-R
Financiación: info:eu-repo/grantAgreement/ES/MINECO/AGL2015-65560-R
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PCIN-2013-065
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SEV-2016-0644

Tipo y forma: Article (PostPrint)

Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)