Characterization of the structure and aggregative property of Arctic-type Aβ40 in lipid environments
| Autor: | Yu Chang, 張愉 |
|---|---|
| Rok vydání: | 2017 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 106 Alzheimer’s disease (AD) is a chronic neurodegenerative disorder. Its pathogenesis has been thought to be associated with β-amyloid peptide (Aβ) aggregation. Aβ contains about 39~42 amino acid residues and it is derived from the sequential cleavage of β-amyloid precursor protein (AβPP). Mutations within the Aβ sequence that cause early onset familial Alzheimer’s disease (FAD) have been shown to promote Aβ aggregation. Arctic mutation (E22G) is one of the FAD mutation, and it reduced the α-helical propensity and conformation stability of Aβ on residues 15-25. According to previous studies, Aβ could interact with lipids. The interaction between Aβ and lipids might alter the structural property and stability of Aβ. However, the molecular mechanism for how Aβ interacts with lipids is still unclear. To understand the interaction mechanism, we used lyso-myristoylphosphatidylglycerol (LMPG) micelles and lyso-myristoylphosphatidylcholine (LMPC) micelles to mimic the membrane environment and applied nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD) spectroscopy, thioflavin-T fluorescence assay, transmission electron microscopy (TEM) to characterize the structure and the aggregative property of Arctic-type Aβ40 (Aβ40(E22G)) in the presence and absence of lipid micelles. Our data suggested that Arctic-type Aβ40 could bind to both types of lipid micelles, and the binding could induce α-helix formation of Arctic-type Aβ40. From a structural perspective, the increase of α-helical propensity of Arctic-type Aβ40 would inhibit its structural transition from α-helix to β-strand, leading to an inhibition of its aggregation. The result of aggregation kinetics showed that the aggregation rate of Arctic-type Aβ40 was inhibited in the presence of both types of lipid micelles. Besides, the effect of lipid charge on the structural and aggregative properties will be discussed as well. These results may help us gain insight into the role of lipid membranes in Aβ aggregation. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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