Nanoscience and Microsystems ETDs

Publication Date

Spring 5-13-2023

Abstract

Although the exact cause of Alzheimer’s disease (AD) is still unknown, it is widely considered that the accumulation of amyloid plaques composed of the amyloid-β (Aβ) peptide in the brain is linked to neurodegeneration. Co-localization of viral DNA with Aβ plaques, the association of brain infection and AD, and research indicating the protective effect of Aβ against bacteria and fungi in mice and human cells have led to the hypothesis that Aβ expression and deposition may be central to its function as an antimicrobial peptide (AMP). In my thesis research, we seek to elucidate how Aβ functions as an AMP by investigating its toxicity toward bacteria, particularly the role aggregation plays in its antimicrobial activity. A computational study was also undertaken to acquire a better understanding of Aβ aggregates' interactions with neuronal and bacterial-mimicking lipid membranes. Later, a molecular dynamics (MD) simulation was performed to examine the effect of methionine (Met35) oxidation on the destabilization of Aβ aggregates, which can potentially lead to its clearance. This research also focused on evaluating and modulating conjugated polyelectrolytes' antibacterial efficacy in solution, as a disinfectant spray, and in hydrogel platforms. In summary, this study revealed the antimicrobial effect of conjugated polyelectrolytes and Aβ aggregates.

Keywords

Alzheimer's Disease, amyloid-β, Antimicrobial Peptides, Conjugated Polyelectrolytes, Molecular Dynamics Simulation, Light-induced antimicrobial activity

Document Type

Dissertation

Language

English

Degree Name

Nanoscience and Microsystems

Level of Degree

Doctoral

Department Name

Nanoscience and Microsystems

First Committee Member (Chair)

Eva Y. Chi

Second Committee Member

David G. Whitten

Third Committee Member

Kiran Bhaskar

Fourth Committee Member

Yi He

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