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Linear dichroism spectroscopy and biophysics of an amyloid protein
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Norton, Stephen R. (2015) Linear dichroism spectroscopy and biophysics of an amyloid protein. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b2870383~S1
Abstract
Though Parkinson’s Disease is known to be caused by cell death in one region of the brain, and though the protein α-synuclein is known to be associated with it, the causes are still poorly understood. It has not yet been shown how α-synuclein may cause cells to die, with research focusing on the range of structures the protein is able to adopt. The classic amyloid fibrils are currently believed to be non-toxic, but smaller, soluble oligomers appear to be the toxic species. Key to toxicity and to the normal function of α-synucein (also unknown to-date) appear to be the ability of the protein to bind to lipids, as toxicity may be due to oligomers forming pores in cells, and the normal function of the protein may be in vesicle transport.
The work presented in this thesis represents a collection of studies, across several disciplines, that test aspects of the behaviour of α-synuclein. Circular dichroism and fluorescence data presented here show that the protein interacts with the lipid POPS in a concentration-dependent manner. Linear dichroism was an important and complementary technique to these, but required some method refinement and sample preparation improvement. This work is presented in this thesis, alongside experimental and theoretical studies into the behaviour of lipid vesicles in Couette flow. It was shown that certain lipids perform better in Couette flow, particularly the mixture of POPC and POPS. This informed the linear dichroism studies, and enabled experiments suggesting that oligomers of α-synuclein may insert across the membrane of vesicles. If confirmed, this would support the amyloid pore theory of α-synuclein toxicity.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QP Physiology | ||||
Library of Congress Subject Headings (LCSH): | Alpha-synuclein | ||||
Official Date: | September 2015 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Molecular Organisation and Assembly in Cells | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Rodger, Alison ; Pinheiro, Teresa J. T. | ||||
Sponsors: | Engineering and Physical Sciences Research Council | ||||
Extent: | xvii, 178 leaves : illustrations, charts | ||||
Language: | eng |
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