Date of Award
Master of Science (MS)
Synucleinopathies are a group of neurodegenerative diseases associated with the intracellular accumulation of aggregated Î±-synuclein, a neurotoxic process resulting in cell death. Research indicates that pathology results from Î±-synuclein misfolding and self-propagation, as well as, cell-to-cell transmission. Furthermore, pathological Î±-synuclein transmission may occur through unconventional secretion.
In this thesis, we investigated how autophagy influences unconventional secretion of our novel Î±-synuclein dual-split protein model that we first verified by reproducing documented results from treatment of known autophagic regulators. Afterwards, we investigated how knocking out autophagic proteins ATG7 and Beclin-1 influenced Î±-synuclein secretion.
Additionally, we developed a methodology for analyzing extracellular vesicles on a single vesicle level using microscopy and immunofluorescent staining which we demonstrate by analyzing the vesicles secreted from SH-SY5Y cells treated with sonicated preformed Î±-synuclein fibrils.
Burbidge, Kevin, "The Unconventional Secretion of Alpha-Synuclein by Autophagic Mechanisms and the Novel Characterization of Pathological Alpha-Synuclein Associated Extracellular Vesicles" (2017). Master's Theses. 3664.
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Copyright © 2017 Kevin Burbidge