Graduation Date

Spring 5-9-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Pathology & Microbiology

First Advisor

Prabagaran Narayanasamy

Abstract

Alzheimer’s Disease is a neurodegenerative condition featuring neural cell death and a decline in cognitive capacity caused by elevated inflammation and production of reactive oxygen species. The glyoxalase pathway is an endogenous antioxidant system that neutralizes reactive methylglyoxal through sequential reactions. Dysfunction of the glyoxalase pathway contributes to oxidative stress and the accumulation of inflammatory metabolic byproducts. Plant-produced compounds with antioxidant activity can enhance endogenous antioxidant pathways and protect cells from elevated ROS production. We hypothesize that flavonoids and limited Cannabis Sativa-produced cannabidiol can enhance glyoxalase pathway function through regulation of antioxidant and pro-apoptotic signaling pathways to prevent methylglyoxal-mediated cellular damage. This research investigates the effects of flavonoids and cannabidiol on glyoxalase pathway function. We also investigated the influence of structural modifications in flavonoid morin to improve its inherent antioxidant activity. We evaluated the effect of flavonoids and CBD on expression of glyoxalase constituents and cell signaling pathways in vitro utilizing primary mouse cerebellar neurons, and in vivo with C. elegans. Our research provides evidence of antioxidant compounds enhancing endogenous glyoxalase pathway activity, and the specific mechanism of cellular signaling pathway modulation.

Frandsen ACS copyright permission pdf.pdf (104 kB)
ACS chemical neuroscience copyright permission

Frandsen redox biology copyright permission pdf.pdf (88 kB)
Redox Biology copyright permission

frandsen scientific reports nature copyright permissions pdf 2.pdf (145 kB)

Available for download on Tuesday, October 27, 2020

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