Date of Graduation

Fall 2025

Degree

Master of Science in Chemistry

Department

Chemistry & Biochemistry

Committee Chair

Tuhina Banerjee

Abstract

Tau protein aggregation is a hallmark of Alzheimer’s disease and related tauopathies, where the formation of toxic oligomeric intermediates leads to neuronal dysfunction and cell death. In this study, the interaction between Tau protein and PEGylated gold nanoparticles (AuNPs-PEG) was investigated to explore their potential role in modulating the fibrillation. The gold nanoparticles were made via a two-step process incorporating thiol-terminated polyethylene glycol (PEG-SH) and characterized using dynamic light scattering (DLS) and localized surface plasmon resonance (LSPR). The effect of AuNP-PEG on the kinetics of Tau aggregation was examined using thioflavin T(ThT), Congo red, and Nile red assays, which investigate β-sheet formation, amyloid binding, and hydrophobicity measurement, respectively. The outcome of the above assays clearly demonstrated that the AuNP-PEG inhibited Tau fibril formation, being able to increase the lag-time period length and decreasing the change into mature fibrils, which inhibited the generation of the more toxic oligomeric intermediate stage. LC-MS analysis confirms that PEGylation alters the proteomic landscape, influencing protein abundance, binding behavior and the biological response. Overall, these findings demonstrate that AuNPs-PEG can act as effective inhibitors of Tau aggregation through modulation of early nucleation events. This study provides mechanistic insight into the design of PEG-based nanoparticle systems as potential nanotherapeutic platforms for mitigating Tau-mediated neurodegeneration in Alzheimer’s disease.

Keywords

Tau protein, PEGylated gold nanoparticles, Alzheimer’s disease, protein aggregation, surface plasmon resonance, nanotherapeutics, neurodegeneration

Subject Categories

Analytical, Diagnostic and Therapeutic Techniques and Equipment | Biochemistry, Biophysics, and Structural Biology | Chemicals and Drugs | Chemistry | Cognitive Behavioral Therapy | Diseases | Medical Sciences | Nanotechnology | Neurology | Neuroscience and Neurobiology | Pharmacy and Pharmaceutical Sciences

Copyright

© Rahab Wanjiru Kanogo

Available for download on Friday, December 01, 2028

Open Access

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