Class Year

2019

Date

4-18-2019

Document Type

Thesis

Distinguished Thesis

Yes

Degree Name

Bachelor of Arts (BA)

Department or Program

Neuroscience

Second Department or Program

Biochemistry and Molecular Biology

First Advisor

Shubhik K. DebBurman

Second Advisor

Michael M. Kash

Third Advisor

Jean-Marie Maddux

Fourth Advisor

Erica E. Schultz

Abstract

Parkinson’s Disease is a devastating neurodegenerative disorder in which loss of voluntary movement occurs due to accumulation of misfolded α-synuclein in the midbrain. In diseased individuals, α-synuclein is covalently modified by multiple chemical groups. The pathological contributions of some modifications are well-studied (phosphorylation and nitration), but those of more recently identified ones (sumoylation, acetylation, and glycation) remain scant. Furthermore, how these modifications in combination influence α-synuclein’s properties is unknown. We used a budding yeast model of Parkinson’s Disease to investigate the effects of these modifications on α-synuclein’s localization, expression, and toxicity. We found that: 1) SUMOylation and acetylation are protective, while phosphorylation and glycation are detrimental; 2) SUMOylation and phosphorylation, as well as acetylation and glycation, counteract each other; 3) and glycation alters the toxicity of several α-synuclein mutants that cause familial Parkinson’s Disease. This study suggests that post-translational modifications are a viable target for manipulating α-synuclein’s pathological properties.

Language

English

Comments

Phi Beta Kappa thesis award, co-winner

Available for download on Monday, May 06, 2024


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