Hyperphosphorylation of the Parkinson’s Disease protein α-Synuclein increases the rate of neurotoxic fibril formation in vitro
Hyperphosphorylation of the Parkinson’s Disease protein α-Synuclein increases the rate of neurotoxic fibril formation in vitro
| dc.contributor.advisor | James, Nicholas | |
| dc.contributor.author | Minami, Remy | |
| dc.contributor.department | Department of Cell and Molecular Biology and Chemistry | |
| dc.date.accessioned | 2019-01-16T23:12:52Z | |
| dc.date.available | 2019-01-16T23:12:52Z | |
| dc.date.issued | 2014 | |
| dc.description.abstract | Parkinson’s disease is a neurological disease that affects approximately 3% of the population over the age of 60 and is the second most common neurodegenerative disorder. PD is characterized by reduced levels of dopamine in the brain due to neuronal death in the substantia nigra. The surviving neurons contain spherical inclusions called Lewy Bodies (LBs) that are composed of a dense aggregation of proteins and lipids. α-Synuclein (aSyn) is the primary protein component of LB’s. Alterations in the expression of aSyn have been shown to affect neurotransmitter (such as dopamine) release. Also, when incubated at 37° C aSyn spontaneously forms fibril structures demonstrating the importance of this protein in LB formation. Hyperphosphorylated aSyn is the major fraction of protein found in LBs. This research project investigated the role of phosphorylation in aSyn aggregation in order to gain insight into the molecular basis of PD. S129E aSyn is a mutation that mimics phosphorylation at serine 129. In this project, wild-type aSyn and S129E aSyn were expressed and purified, and the rate of fibril formation was compared using a Thioflavin T fluorescence assay. The Thioflavin T assay showed a threefold increase in the rate of fibril formation in the S129E aSyn, consistent with a disease model in which hyper-phosphorylated aSyn increases the likelihood of formation of neurotoxic fibrils. The confirmation of the importance of phosphorylation in LB formation provides a molecular basis into the pathogenesis of PD and suggests further research on protein kinases that phosphorylate aSyn as a promising area of future research. | |
| dc.format.extent | 21 pages | |
| dc.identifier.uri | http://hdl.handle.net/10125/61645 | |
| dc.publisher | University of Hawaii at Manoa | |
| dc.rights | All UHM Honors Projects are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner. | |
| dc.title | Hyperphosphorylation of the Parkinson’s Disease protein α-Synuclein increases the rate of neurotoxic fibril formation in vitro | |
| dc.type.dcmi | Text |
Files
Original bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- Minami_Remy_Honors_Project_uh.pdf
- Size:
- 1.64 MB
- Format:
- Adobe Portable Document Format
- Description:
- Must be a UH user to access.