| Summary: | 碩士 === 國立臺灣大學 === 化學研究所 === 107 === Aggregates of β-amyloid peptide （Aβ） are an important pathological signature of Alzheimer''s disease （AD）. Currently, various Aβ aggregates such as oligomers, protofibrils, and fibrils are widely considered as the key factors controlling the progression of AD. For therapeutic treatments, we need to determine the molecular structure of Aβ aggregates. However, Aβ aggregates prepared in vitro are highly polymorphic. We hypothesize that the structure polymorphism is a direct consequence of the coexistence of various nucleation pathways, viz., the primary nucleation, fibril fragmentation, and the fibril-assisted secondary nucleation. In order to get a monomorphic structure of Aβ fibrils, we attempt to use nano-sized reverse micelle as a physically confined space to incubate Aβ peptides so that the peptides are trapped into their oligomeric state. After the backward extraction of the peptides from the reverse micelles, oligomers could be used to seed the fibrillization of Aβ monomers. In this way, Aβ monomers could aggregate mainly through the primary nucleation pathway, from which we should be able to get monomorphically structured Aβ fibrils. In our earlier studies, the surfactant, Aerosol-OT （AOT） was used to prepare reverse micelles to encapsulate Aβ peptides. Unfortunately, the residual AOT after backward extraction would interfere the aggregation kinetics of Aβ monomers. In this study, we therefore chose the phosphatidylcholine extracted from soybean, which is a bio-compatible amphiphilic molecule, to prepare our reverse micelles. We aim to verify our hypothesis on the structural polymorphism of Aβ aggregates by this newly developed reverse micelles. In the subsequent seeding experiments, the oligomers of different incubation time in PC-RM show different properities. Compared to the oligomers of shorter incubation time, oligomers with longer incubation time in PC-RM tend to have a minor seeding ability but stronger toxicity in cell vability test. We suggest that the results are cause by stronger interactions between the lipid molecules and the Aβ oligomers for longer incubation time in PC-RM.
|
|---|
