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Date of Award


Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science



First Advisor

Dr. John Warrick


Machado Joseph Disease (MJD) is one of the most common dominantly inherited ataxias worldwide and is caused by an expansion of the CAG repeat in the ataxin-3 (Atx3) gene. The disease is hallmarked by the presence of Atx3 protein aggregates and late-onset degeneration. Increased reactive oxygen species (ROS) have been observed in neurodegenerative diseases like MJD, so it has been suggested that increased antioxidant activity may be beneficial as it removes harmful ROS. However, previous research in our lab has shown that increased Sod2 antioxidant expression increases disease progression. Because ROS play a role in autophagy induction, we believe this may be due to disrupted autophagy. To study this, we have modeled MJD in Drosophila melanogaster. We analyzed GFP autophagic degradation and observed greater dysfunction in flies expressing the diseased form of the protein compared to controls. To gain greater insight into the pathology, we visualized several autophagic-related proteins in diseased and non-diseased flies expressing wild-type or increased levels of Sod2 antioxidant. We found several differences suggestive of greater autophagic dysfunction in diseased flies expressing increased levels of Sod2. To further analyze the role of autophagy and ROS in disease progression, we upregulated autophagy using rapamycin while also increasing SOD2 antioxidant. Preliminary results suggest the greatest rescue of diseased neurons with combined treatment of increased Sod2 and rapamycin in diseased flies. This result suggests that decreased ROS may be beneficial to the cells when autophagy is still properly induced.