Date of Award

2017

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Neuroscience

Abstract

Synucleinopathies are a group of neurodegenerative diseases associated with the intracellular accumulation of aggregated α-synuclein, a neurotoxic process resulting in cell death. Research indicates that pathology results from α-synuclein misfolding and self-propagation, as well as, cell-to-cell transmission. Furthermore, pathological α-synuclein transmission may occur through unconventional secretion.

In this thesis, we investigated how autophagy influences unconventional secretion of our novel α-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 α-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 α-synuclein fibrils.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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