Year: 2018
Type: dissertation
Abstract: The synucleinopathies are progressive, neurodegenerative diseases of aging characterized by the accumulation of α-synuclein aggregates. α-Synuclein aggregates are prion-like and amplify in a prion-like manner. A key feature of prions is the existence of different strains, where depending on the conformation, a different prion disease is manifested. The existence of α-synuclein aggregate strains is an area of active research and provides a potential explanation for the clinical heterogeneity of the synucleinopathies. The overarching aim of this project was to investigate α-synuclein’s ability to form strains and understand their biological consequences. Using recombinant protein, we created and characterized two unique strains of α-synuclein fibrils, which induced different clinicopathological disease phenotypes in a mouse model (TgM83 mice). This approach provides evidence that conformational differences alone are sufficient for causing different disease phenotypes, demonstrating α-synuclein’s ability to form strains and that strains may be biologically relevant to disease pathogenesis.
Source: TSpace (University of Toronto)
Author: Angus Lau
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3151085095