Electronic Thesis and Dissertation Repository


Master of Science




Dr. Robert Cumming


Huntington’s disease (HD) is a fatal neurodegenerative disorder resulting from the expansion of a trinucleotide repeat within the HD gene. At the cellular level mutant HTT (mHTT) aggregates perturb cellular metabolism, intracellular trafficking and mitochondrial function, resulting in the increased production of reactive oxygen species (ROS) an event closely linked with nerve cell death. Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-sensitive transcription factor responsible for transcribing neuroprotective genes under the control of the antioxidant response element (ARE), which work to counteract high intracellular ROS levels. I have identified significant increases in cell viability, NRF2 nuclear localization, and ARE-luciferase reporter activity following treatment with the NRF2 activator dimercaptopropanol (DMP). DMP was also found to increase ARE-directed gene expression and maintain a greater proportion of functionally active peroxiredoxin 1 (PRX1) protein levels, resulting in increased neuronal survival. For this reason DMP may serve an important role in treating HD.