Eterogeneità delle proprietà fisico – chimiche della proteina prionica patologica e variabilità fenotipica ceppo specifica nella malattia di Creutzfeldt – Jakob

Cescatti, Maura (2011) Eterogeneità delle proprietà fisico – chimiche della proteina prionica patologica e variabilità fenotipica ceppo specifica nella malattia di Creutzfeldt – Jakob, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biochimica, 22 Ciclo. DOI 10.6092/unibo/amsdottorato/3717.
Documenti full-text disponibili:
[img] Documento PDF (Italiano) - Accesso riservato - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Download (4MB)

Abstract

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are neurodegenerative disorders that affect humans and mammals. Creutzfeldt-Jakob disease (CJD), the most common TSE in humans, can be sporadic (sCJD), genetic (gCJD), or acquired by infection. All TSEs are characterised by the accumulation of PrPSc, a misfolded form of the cellular protein PrPC. PrPSc is insoluble in detergents, partially resistant to proteolysis and shows a highly enriched β-sheet secondary structure. Six clinico-pathological phenotypes of sCJD have been characterized which correlate at the molecular level with two types (1 or 2) of PrPSc with distinctive physicochemical properties and the genotype at the polymorphic (methionine or valine) codon 129 of the prion protein gene. According to the protein-only hypothesis, which postulates that prions are composed exclusively of PrPSc, the strains of prions that are largely responsible for the wide spectrum of TSE phenotypes are enciphered in PrPSc conformation. In support to this view, studies mainly conducted in experimental scrapie, have shown that several prion strains can be identified based on distinguishing PrPSc biochemical properties. To further contribute to the understanding of the molecular basis of strains and to develop more sensitive strain typing assays in humans we have analyzed PrPSc biochemical properties in two experimental setting. In the first we compared the size of the core after protease digestion and the glycoform pattern of PrPSc before and after transmission of human prions to non human primates or bank voles, whereas in the second we analyzed the conformational stability of PrPSc associated with sCJD, vCJD or fCJD using guanidine hydrochloride (GdnHCl) as denaturant. Combining the results of the two studies, we were able to distinguish five human strains for at least one biochemical property. The present data extend our knowledge about the extent of strain variation and its relationship with PrPSc properties in human TSEs.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Cescatti, Maura
Supervisore
Dottorato di ricerca
Scuola di dottorato
Scienze biologiche, biomediche e biotecnologiche
Ciclo
22
Coordinatore
Settore disciplinare
Settore concorsuale
URN:NBN
DOI
10.6092/unibo/amsdottorato/3717
Data di discussione
7 Giugno 2011
URI

Altri metadati

Gestione del documento: Visualizza la tesi

^