Type of Document Dissertation Author Lemkul, Justin Alan Author's Email Address email@example.com URN etd-03122012-104455 Title Molecular Modeling of the Amyloid β-Peptide: Understanding the Mechanism of Alzheimer's Disease and the Potential for Therapeutic Intervention Degree PhD Department Biochemistry Advisory Committee
Advisor Name Title Bevan, David R. Committee Chair Helm, Richard Frederick Committee Member O'Keefe, Sean F. Committee Member Santos, Webster L. Committee Member Sobrado, Pablo Committee Member Keywords
- Protein-lipid interactions
- Free energy calculations
Date of Defense 2012-03-07 Availability unrestricted AbstractAlzheimer's disease is the leading cause of senile dementia in the elderly, and as life expectancy increases across the globe, incidence of the disease is continually increasing. Current estimates place the number of cases at 25-30 million worldwide, with more than 5.4 million of these occurring in the United States. While the exact cause of the disease remains a mystery, it has become clear that the amyloid β-peptide (Aβ) is central to disease pathogenesis. The aggregation and deposition of this peptide in the brain is known to give rise to the hallmark lesions associated with Alzheimer's disease, but its exact mechanism of toxicity remains largely uncharacterized.
Molecular dynamics (MD) simulations have achieved great success in exploring molecular events with atomic resolution, predicting and explaining phenomena that are otherwise obscured from even the most sensitive experimental techniques. Due to the difficulty of obtaining high-quality structural data of Aβ and its toxic assemblies, MD simulations can be an especially useful tool in understanding the progression of Alzheimer's disease on a molecular level.
The work contained herein describes the interactions of Aβ monomers and oligomers with lipid bilayers to understand the mechanism by which Aβ exerts its toxicity. Also explored is the mechanism by which flavonoid antioxidants may prevent Aβ self-association and destabilize toxic aggregates, providing insight into the chemical features that give rise to this therapeutic effect.
Filename Size Approximate Download Time (Hours:Minutes:Seconds)
28.8 Modem 56K Modem ISDN (64 Kb) ISDN (128 Kb) Higher-speed Access Lemkul_JA_D_2012.pdf 24.87 Mb 01:55:07 00:59:12 00:51:48 00:25:54 00:02:12 Lemkul_JA_D_2012_Copyright.pdf 814.40 Kb 00:03:46 00:01:56 00:01:41 00:00:50 00:00:04
If you have questions or technical problems, please Contact DLA.