Epitope scanning indicates structural differences in brain-derived monomeric and aggregated mutant prion proteins related to genetic prion diseases.
Biochem J
; 454(3): 417-25, 2013 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-23808898
ABSTRACT
Genetic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia and prion protein cerebral amyloid angiopathy are clinically and neuropathologically distinct neurodegenerative diseases linked to mutations in the PRNP gene encoding the cellular prion protein (PrPC). How sequence variants of PRNP encode the information to specify these disease phenotypes is not known. It is suggested that each mutation produces a misfolded variant of PrPC with specific neurotoxic properties. However, structural studies of recombinant PrP did not detect major differences between wild-type and mutant molecules, pointing to the importance of investigating mutant PrPs from mammalian brains. We used surface plasmon resonance and a slot-blot immunoassay to analyse the antibody-binding profiles of soluble and insoluble PrP molecules extracted from the brains of transgenic mice modelling different prion diseases. By measuring the reactivity of monoclonal antibodies against different PrP epitopes, we obtained evidence of conformational differences between wild-type and mutant PrPs, and among different mutants. We detected structural heterogeneity in both monomeric and aggregated PrP, supporting the hypothesis that the phenotype of genetic prion diseases is encoded by mutant PrP conformation and assembly state.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Priones
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Enfermedad de Gerstmann-Straussler-Scheinker
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Síndrome de Creutzfeldt-Jakob
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem J
Año:
2013
Tipo del documento:
Article
País de afiliación:
Italia