Bachelor of Arts (BA)
Department or Program
Second Department or Program
Biochemistry and Molecular Biology
Shubhik K. DebBurman
Michael M. Kash
Erica E. Schultz
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.
Ganev, Yoan Petrov, "Combinatorial Impact of α-Synuclein Post-Translational Modifications in Yeast" (2019). Senior Theses.
Available for download on Monday, May 06, 2024