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Effects of Curcumin and Dredd in a Drosophila model of Machado-Joseph Disease
Date of Award
Restricted Thesis: Campus only access
Bachelor of Science
Dr. John Warrick
Machado-Joseph Disease (Spinocerebellar Ataxia Type 3, SCA3) is a member of the polyglutamine family of human neurodegenerative diseases. Mechanisms of pathogenesis are poorly understood but it has been suggested that overstimulation of the Innate Immune Response (IIR) may impact neurodegeneration. It has been shown that upregulating the expression of Relish, the Drosophila homolog and for human NF-κB, increases neurodegeneration as shown through the loss of Drosophila retinal photoreceptors. Therefore, I chose to regulate expression of the IIR upstream of Relish to determine the impact on neurodegeneration through two different studies. The first focused on curcumin, a known antioxidant and anti-inflammatory agent, as it has been proven to prevent NF-κB from translocating into the nucleus in humans. However, curcumin did not decreased neurodegeneration in our model but instead increased tissue quality and overall organization of ommatidia, suggesting that curcumin did not inhibit Relish. In the second study, I modulated the regulation of Dredd, a caspase which activates Relish through cleaving Relish’s inhibitory region. Based on preliminary data, both upregulation and downregulation of Dredd led to a loss of photoreceptors and increase in neurodegeneration. Surprisingly this data also suggests that downregulating Dredd may have an impact on retinal development in our control, non-disease expressing flies.
Warde, Grace, "Effects of Curcumin and Dredd in a Drosophila model of Machado-Joseph Disease" (2020). Honors Theses. 1531.