Investigation on the mechanism of amyloid beta peptides oligomerization and the process for its inhibition

• Main Author: Zhao, Li Na
• Other Authors: Mu Yuguang
• Format: Theses and Dissertations
• Language: English
• Published: 2013
• Subjects: DRNTU::Science::Biological sciences::Biophysics
• Online Access: https://hdl.handle.net/10356/55043
• Institution: Nanyang Technological University

Amyloid beta (Abeta) plaque, which is a characteristic hallmark of Alzheimer’s disease (AD), results from the deposition of Abeta peptides. Amyloid beta peptides are prone to self assembly into high-order oligomers, which is the major pathological pathway of AD. It is generally believed that the Abeta oligomers are the main source of toxicity and the leading contributor to neuronal cell death. Amyloid beta oligomers are transient structures with no regular secondary structure. They are easily attached to membrane and other molecules. Thus, it is difficult to study them purely based on conventional experimental approaches. Hence, it is the goal of my research to use computational methodologies to reveal the mechanisms of Abeta aggregation in aqueous and membrane environment and the influence of small molecules like curcumin and heme, and the inflammatory proteins like S100A9, on Abeta oligomerization. We have chosen the full-length Abeta peptides as well as the most representative short segments of Abeta and employed the classical molecular dynamics and the sampling-enhanced replica exchange molecular dynamics simulations, to investigate the aggregation and atomic detailed interaction among Abeta, lipids, small molecules and macromolecules.