Characterization of the effects of lipid micelles on the aggregation behavior of β-amyloid peptide

• Main Authors: Chu-Ting Liang, 梁筑婷
• Other Authors: Ta-Hsien Lin
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/gt577m

博士 === 國立陽明大學 === 生命科學系暨基因體科學研究所 === 107 === Alzheimer's disease (AD) is the most common form of dementia. It is thought to be associated with aggregation of β-amyloid peptide (Aβ). The aggregation of Aβ is a complex process which involves conformational transitions and self-assembly, suggesting that the structural stability of Aβ play a determinant role in Aβ aggregation. It has been reported that Aβ can interact with cellular membranes and form Aβ aggregates. Studies have also shown that lipids may induce conformational transitions of Aβ and promote the aggregation process. These results suggested that the interactions of Aβ with lipids may lead to alternations of the structural property and conformational stability of Aβ. The molecular mechanism for how Aβ interacts with lipids remains unclear. To understand the Aβ-lipid interaction mechanism, the role of lipids in the aggregation behavior of Aβ were characterized by circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy, thioflavin-T (Th-T) fluorescence assay and transmission electron microscopy (TEM). We used LMPG (lyso-myristoyl phosphatidylglycerol) micelles (anionic micelles), LMPC (lyso-myristoyl phosphatidylcholine) micelles (zwitterionic micelles) as a model system to investigate the interaction mechanism of Aβ with lipids. Comparisons of the structures and aggregation behavior of Aβ40 in the presence and absence of lipids may provide useful information for elucidating the interaction mechanism from the structural point of view. Structural studies suggested that Aβ40 could interact with LMPG and LMPC micelles and the interaction could induce conformational changes of Aβ40。Aggregation kinetics indicated that lipids inhibited the aggregation of Aβ40. We also investigated the effects of L17A/F19A replacements on the interaction and aggregation of Aβ40 in lipid environments. We obtained that L17A/F19A substitutions increase α-helicity but did not enhance the strength of Aβ-lipid interaction. These results suggested that L17A/F19A replacements may increase intrinsic α-helical propensity and reduce the aggregation rates of Aβ40 in lipid micelles. These findings may help us gain more insight into the role of lipids in Aβ aggregation process from the structural point of view.