The aim of the thesis project was to examine what form(s) of Amyloid beta (Aβ) (25-‐35) peptide interact with phospholipids in vitro and the implications of this for the mechanism of Alzheimer’s Diseases (AD). The mechanism of AD is thought to involve protein folding and misfolding. An increasing amount of evidence has shown that protein misfolding plays an important role in the biological and pathological processes of AD. Although seen as the biomedical markers of those diseases, the roles of amyloid aggregates themselves are still not fully understood. Whether the aggregates, or the monomer, or some other intermediates of Aβ cause AD is still unknown. In order to investigate the membrane-‐interaction of Aβ and its implications for AD, two forms of Aβ, namely levorotary and dextrorotary (L-‐ and D-‐) Aβ isomers were used. Evidence has shown that L-‐ and D-‐ peptide can each form aggregates in a humid environment. However, when mixed together, L-‐ and D-‐ peptides tend not to form any aggregates. Using the mixtures of L-‐ and D-‐ peptides at different proportions and as well as using L-‐ and D-‐ alone can help us to determine the toxic form of Aβ. Phospholipids have been used to mimic membrane bilayers. Biological membranes in vivo are a complicated system. They contain three types of lipids, namely phospholipids, glycolipids, and steroids. Different types of cells and different membranes have different proportions of those lipids. Studying the interaction between Aβ and membranes in vivo can be extremely difficult. Artificial membranes, which only contains one kind of lipids, on the other hand, are a useful tool for the study of molecular interactions. Phospholipids are the most abundant type of membrane lipid and thus that can be seen as representative of cell membranes. The interactions of Aβ and different kinds of phospholipids have been investigated in this project. This thesis discusses the secondary structure of Aβ in different environment, the interaction between Aβ and phospholipids at the air-‐water surface, and the location of Aβ in membranes during the interaction. The study provides useful information of the mechanisms and the origin of AD. At the end of the thesis, a discussion chapter analyses the difficulties of studying Aβ and AD and the potentials and inadequacies of this research.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:743586 |
| Date | January 2015 |
| Creators | Ma, Xin |
| Contributors | Bradshaw, Jeremy ; Diaz, Mary |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/29637 |
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