The main goal of this research is to provide a novel bioanalytical approach to better understand α-synuclein (AS) aggregation linked to Parkinson’s disease (PD) and characterize the implications of contributing factors such as the presence of metal ions and potential therapeutics that would inhibit or reverse AS fibrillation. Current bioanalytical techniques have reported the fibrillation process of AS however, the detection of prefibrillar formation or the nucleation phase of AS has yet to be characterized. This research aimed to address this issue and monitor the primary stages of AS fibrillation from natively soluble monomer to fibrillar aggregates. The electrochemical measurement of these processes utilized the intrinsic electroactivity of 4 tyrosine (Tyr) residues in AS observed at ~0.6 V (vs. Ag/AgCl) to monitor its early fibrillation kinetics. The research presented here provided valuable evidence of the conformational changes attributed to prefibrillar forms of AS.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/29507 |
| Date | 23 August 2011 |
| Creators | Chan, Tiffiny |
| Contributors | Kerman, Kagan |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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