Information Services banner Edinburgh Research Archive The University of Edinburgh crest

Edinburgh Research Archive >
Molecular, Genetic and Population Health Sciences, School of >
Molecular, Genetic and Population Health Sciences thesis and dissertation collection >

Please use this identifier to cite or link to this item:

This item has been viewed 64 times in the last year. View Statistics

Files in This Item:

File Description SizeFormat
Choi2010.docFile not available for download84.8 MBMicrosoft Word
Choi2010.pdfPhD thesis3.8 MBAdobe PDFView/Open
Title: PrPSc complexity in different forms of Creutzfeldt-Jakob disease identified using biochemical approaches
Authors: Choi, Young Pyo
Supervisor(s): Head, Mark
Ironside, James
Issue Date: 2010
Publisher: The University of Edinburgh
Abstract: Transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative diseases affecting humans and animal species. Prion diseases are characterized by the conversion of the host encoded prion protein (PrPC) into a disease-associated isoform (PrPSc), which (according to the prion hypothesis) is thought to be the main component of the infectious agent. PrPSc has been traditionally distinguished from PrPC by its biochemical properties, such as partial resistance to proteolysis and detergent-insolubility. In the absence of a foreign nucleic acid genome associated with prion diseases, efforts to provide a molecular basis for the biological diversity of prions have focused on biochemical characterization of PrPSc. In Creutzfeldt-Jakob disease (CJD) and other forms of human prion disease, the biochemical characterization of PrPSc has been largely restricted to the analysis of PK-resistant fragments of PrPSc (PrPres) by Western blot. However, given recent findings on the complexity of PrPSc identified in laboratory prion strains, PrPres analysis alone may not provide a complete description of PrPSc present in CJD brains. For a more complete characterization of PrPSc in human prion diseases, this study investigated biochemical properties of PrPSc in different forms of CJD by employing approaches that differ in principle from conventional Western blot analysis of PrPres. The novel biochemical approaches used in this study have identified further complexity of PrPSc accumulated in CJD brains, not only between different forms of CJD but also within single cases of individual disease entities. In this study, the two biochemical criteria most frequently used to define PrPSc (3F4 epitope accessibility versus resistance to limited proteolysis) did not always correlate, indicating probable non-uniform distribution of PK-sensitive isoform of PrPSc within the same CJD brains. In variant CJD (vCJD) brains, the thalamic region, which is characterized by distinct neuropathological features, could also be distinguished from frontal cortex and cerebellum by the sedimentation profiles of PrPC and PrPSc on sucrose step gradients. Moreover, the conformational stability of PrPSc was found not to be uniform among human prion diseases and did not correlate with PrPres type or prion protein genotype. Taken together, the results from this study provide a more complete description of PrPSc species occurring in CJD brains and contribute to a fuller understanding of the agents and the disease processes involved in humans.
Keywords: prion
Creutzfeldt-Jakob disease
Appears in Collections:Molecular, Genetic and Population Health Sciences thesis and dissertation collection

Items in ERA are protected by copyright, with all rights reserved, unless otherwise indicated.


Valid XHTML 1.0! Unless explicitly stated otherwise, all material is copyright © The University of Edinburgh 2013, and/or the original authors. Privacy and Cookies Policy