Dissertation Defense Announcement:
To: The George Mason University Community

Wenling Eileen Chang
PhD Bioinformatics & Computational Biology Candidate

Date:   Thursday April 28, 2011
Time:   11:00 a.m. 
Place:  George Mason University
 	     Occoquan Bldg. Room 203
	     Prince William campus
  
Dissertation Chair: Dr. Dmitri Klimov
Committee members: Dr. Saleet Jafri, Dr. Iosif Vaisman, Dr. Estele Blaisten-Barojas

Title: "Computational Modeling of Anti-Aggregation Effect of Non-Steroidal
           Anti-Inflammatory Drugs in Alzheimer's Amyloidogenesis"

The dissertation is on reserve in the Johnson Center Library, Fairfax campus.
The doctoral project will not be read at the meeting, but should be read in advance. 

All members of the George Mason University community are invited to attend.


ABSTRACT:

Alzheimer’s disease (AD) represents a growing biomedical, social, and economical problem. Studies have shown that aggregated forms of amyloid β peptide adversely affect neuronal function and may represent the causative agent in AD. It has been demonstrated that chronic treatment with ibuprofen and naproxen reduces the risk of AD and improves the behavioral impairment for patients with AD. This dissertation utilizes high performance parallel computing, all-atom molecular dynamics simulation, and protein-ligand docking to understand the mechanism of the anti-aggregation effect of ibuprofen and naproxen in Alzheimer’s amyloidogenesis. The results reveal different mechanisms of ligand binding to the monomers and fibrils formed by Aβ peptides implicated in AD. Binding to Aβ monomers is mostly governed by ligand-amino acid interactions, whereas binding to the fibril is determined by the fibril surface geometry and interligand interactions. The anti-aggregation effect of ibuprofen and naproxen is explained by direct competition between these ligands and incoming Aβ peptides for binding to the fibril.

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