Date of Award

Summer 2022

Project Type

Thesis

Program or Major

Biochemistry

Degree Name

Master of Science

First Advisor

Krisztina Varga

Second Advisor

Feixia Chu

Third Advisor

Sarah R Walker

Abstract

Ursolic acid (UA) is a naturally occurring triterpenoid found in a variety of plants and berries. This molecule has potent antioxidant and anti-inflammatory properties with the potential to treat a wide variety of conditions, including neuro-inflammatory disorders. However, the exact mechanism of action for UA is unknown. In this thesis, the fundamental biochemistry of UA was investigated by studying two potential targets: lipid rafts and protein phosphatases. Lipid rafts are an important platform for a wide variety of signal transduction pathways and are a docking point for the assembly of the pro-inflammatory NADPH oxidase 2. The impact of UA on lipid raft formation in neuronal cells was investigated using confocal microscopy. Protein phosphatases are also implicated in many neurological diseases; in particular, the human protein phosphatase 2C (PP2C) is known to cause apoptotic and neurodegenerative effects. The effects of UA on folding on RsbX, a representative protein serine phosphatase from Bacillus subtilis which highly resembles PP2C, were investigated using circular dichroism spectroscopy. It was found that UA does not significantly impact the folding of the protein phosphatase, but it does alter the dynamics of lipid raft microdomains in neuronal cells. Taken together, these results indicate an anti-inflammatory mechanism of UA involving lipid raft perturbation and provide support for the future development of UA as an anti-neuro-inflammatory or anti-lipid raft treatment.

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