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Date of Award
Restricted Thesis: Campus only access
Bachelor of Science
Dr. John Warrick
Machado-Joseph disease, also known as Spinocerebellar Ataxia Type 3 (SCA3), is the most commonly inherited spinocerebellar ataxia neurodegenerative disease (Costa & Paulson, 2012). SCA3 is characterized by an elongated polyglutamine repeat in the coding region of the ataxin-3 (ATXN3) gene located on chromosome 14q32.1. The non-diseased population the CAG repeat consists of 13-36 residues (Yawaguci et al., 1994). This autosomal dominant neurodegenerative disorder is pathologically diagnosable around 52-86 trinucleotide repeat expansions. There is much evidence suggesting longer CAG repeats are likely indicative of earlier clinical symptoms and disease onset. SCA3 disease onset is typically between ages of 20 and 50, with mean age of onset at 37 years (Paulson, 2012).
In our research, we are investigating if constitutive activation of NF-kB and excessive inflammation impacts SCA3 pathogenesis in Drosophila melanogaster model organisms. In D. melanogaster, there are two evolutionary conserved NF-kB like pathways; the Toll and Immune deficient (Imd) pathways (Zhai et al., 2018). In this study, we focus on the Imd pathway, which is activated by gram-negative bacteria, initiating an NF-kB-like antimicrobial response (Hetru & Hoffman, 2009; Ganeson et al., 2011). The NF-kB homolog in D. melanogaster called Relish similarly becomes activated through signaling cascades leading to cleavage and nuclear translocation, resulting in expression of immune-regulator genes.
Godschall, Lizzie, "The impact of curcumin on neurodegeneration & neuroinflammation in a Drosophila melanogaster model of human Machado-Joseph Disease" (2020). Honors Theses. 1435.