Theses and Dissertations

ORCID

https://orcid.org/0009-0009-0394-5038

Advisor

Krishnan, Natraj

Committee Member

Rai, Aswathy

Committee Member

Collins, Galen

Date of Degree

5-16-2025

Original embargo terms

Visible MSU Only 1 year

Document Type

Graduate Thesis - Campus Access Only

Major

Agricultural Life Sciences (Biochemistry)

Degree Name

Master of Science (M.S.)

College

College of Agriculture and Life Sciences

Department

Department of Biochemistry, Nutrition and Health Promotion

Abstract

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by a CAG repeat expansion in the ataxin-1 gene, which results in an abnormally long polyglutamine tract. Similarly, overexpression of wildtype Ataxin-1 (wt-Atx-1) in Drosophila melanogaster leads to neurodegeneration, reduced lifespan, and impaired negative geotaxis. Observations include disruptions in sleep-wake cycles, increased oxidative stress biomarkers (like protein carbonyls), and dysregulation of developmental genes such as armadillo (arm) and nemo kinase (nmo). Additionally, elevated expression of SUMOylation-related genes (Aos-1, Uba2, and dSmt3 or dSumo) and increased SUMO protein levels indicate enhanced SUMOylation in the brain. Quantitative analysis of neuronal degeneration in SCA1 flies reveals significantly greater neurodegeneration compared to controls. These results highlight the disruptions in sleep-wake cycles and roles of oxidative stress, gene dysregulation, and SUMOylation in SCA1 pathogenesis.

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