Treatment with the alpha-Synuclein Oligomer Prone Mutants E35K and E57K Leads to Significant Intracellular Aggregation and Inclusion Formation
Year: 2015
Type: dissertation
Abstract: Alpha-synuclein (α–syn) is a key neuronal protein that undergoes pathogenic conformational changes and accumulates in Parkinson’s disease. Currently α–syn oligomers have gained a lot of attention as being a particularly toxic version of the protein. This work aims to characterize the aggregation seeding properties of these oligomers. Cells were treated with either oligomeric (E35K or E57K) or fibrillar versions of α–syn. Intracellular changes were assessed using cellular fractionation, fluorescent imaging, and in vitro protein fragment complementation assays. The results from this study highlight the ability of the E35K and E57K treatments to induce changes in α–syn solubility to a greater extent than fibrillar forms of the protein. Exposure to either E35K or E57K also caused the formation of α–syn inclusions that appeared to be transmissible to naïve neighbouring cells. This study highlights interesting properties potentially attributable to α–syn oligomers that merit further investigation.
Source: TSpace (University of Toronto)
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2599066163