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Prion infections and tauopathy in animal models: disease progression and proteolysis

  • Author / Creator
    Eskandari-Sedighi, Ghazaleh
  • Neurodegenerative diseases are a rising concern worldwide. Currently 10% of people aged 65 or more are diagnosed with a neurodegenerative disease and this number is predicted to triplicate by 2050. In developed societies approximately one percent of the global gross domestic product is allocated to the cost of care of affected patients. Aggregation and deposition of misfolded protein species is the common feature in almost all these diseases, hence the name protein misfolding diseases. With lack of any mechanism-based therapeutics, understanding the detailed molecular events contributing to disease pathogenesis is extremely important towards finding an efficient cure for these diseases. Herein, I have applied biochemical techniques to study different aspects of protein misfolding diseases caused by two well-known proteins, tau and the cellular prion protein, in cell and animal models:1) Using a transgenic animal model of tauopathy, I have analyzed the role of different conformations of misfolded protein species in disease pathogenesis and phenotypic heterogeneities observed amongst different patients. 2) I have investigated the molecular transition of scrapie prion protein in a prion disease mouse model. And I have assessed disease-associated symptoms at different timepoints to identify the misfolded protein species in charge of triggering pathogenesis.3) I have investigated the cell and biochemical details of a proteolytic processing event that targets a mutant allele of the prion protein with higher tendency than the wildtype form, with the aim to validate this model as a reliable platform to study the enzymology of this processing event.In summary, the projects discussed in this thesis entail biochemical analysis of disease pathogenesis in tauopathies and prion diseases, with a focus on the impact of proteolytic processing in health and disease conditions.

  • Subjects / Keywords
  • Graduation date
    Fall 2020
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/r3-ngvh-s023
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.