Biomedical Engineering ETDs

Publication Date

Summer 7-31-2019

Abstract

The abnormal misfolding and aggregation of intrinsically disordered proteins into ordered fibrillar amyloid aggregates is recognized as a common pathological event in neurodegenerative disorders (ND) such as Alzheimer’s and Parkinson’s diseases. The key role of fibrillar and pre-fibrillar aggregates in ND makes them ideal biomarkers to better understand disease progression but also for early disease detection and therapeutic intervention. The work described herein was conducted to gain a better understanding of amyloid interaction to lipid membrane and its role in peptide toxicity. This research was also focused on evaluating the fluorescent probe, oligomeric p-phenylene ethynylene (OPE), as an amyloid sensor detecting disease-relevant pre-fibrillar and fibrillar aggregates both in vitro and in biological samples. Finally, OPE’s capability to selectively photo-oxidize amyloid fibrils to ensure their disassembly and clearance was investigated. Taken together, this study revealed the potential of OPE as a theranostic agent for neurodegenerative disorders.

Language

English

Keywords

neurodegenerative disorders, membrane-mediated fibrillation, oligomeric p-phenylene ethynylenes, amyloid aggregate detection, fluorescent optical probe, photo-oxidation

Document Type

Dissertation

Degree Name

Biomedical Engineering

Level of Degree

Doctoral

Department Name

Biomedical Engineering

First Committee Member (Chair)

Eva Y. Chi

Second Committee Member

David G. Whitten

Third Committee Member

Kiran Bhaskar

Fourth Committee Member

Harshini Mukundan

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