Date of Award

2019

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Interdisciplinary Neuroscience

Department

Interdisciplinary Neuroscience

First Advisor

Navindra Seeram

Abstract

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder that has no cure, no therapies to stop the disease progression, and limited palliative care options. As the 6th leading cause of death in the United States, it is necessary to discover therapeutics which can alter disease progression to alleviate the burden on patients, caregivers, and healthcare systems. In the search of therapeutics for AD, dietary polyphenols have become the topic of research as epidemiological evidence suggests that exposure to dietary polyphenols, such as a Mediterranean diet, over one’s life, reduces the risk of dying from AD. Additionally, evidence from rodent models of AD suggests that dietary polyphenols can reduce the severity of cognitive decline and attenuate neuroinflammation, which is thought to be a contributing factor to disease progression. Because of these findings, several dietary polyphenols have entered the clinic in an attempt to elucidate their potential beneficial effects. For example, curcumin, from the curry spice turmeric (Curcuma longa), and resveratrol, a phytoalexin stilbene found in a variety of plants, have been investigated in AD disease populations in phase I and II clinical studies. However, these agents have only had moderate to little success which increases the demand for novel dietary polyphenols leads that may have potentially beneficial effects in the treatment of AD. Due to this demand, this dissertation investigates novel polyphenols and gut metabolites of dietary polyphenols from a variety of dietary sources for potential efficacy in a Caenorhabditis elegans (C. elegans) model of AD. This dissertation also employs molecular biology and mass spectrometry techniques to elucidate the potential mechanisms of action of select compounds found to be efficacious in a C. elegans model of AD. Finally, a polyphenol-enriched extract was evaluated in a murine model of AD for the potential to reduce neuroinflammation when administered orally.

Available for download on Monday, April 19, 2021

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