Class Year




Document Type


Distinguished Thesis


Degree Name

Bachelor of Arts (BA)

Department or Program


Second Department or Program


First Advisor

Shubhik K. DebBurman

Second Advisor

Alexander W. Shingleton

Third Advisor

Naomi Wentworth

Fourth Advisor

Hongkyun Kim, Rosalind Franklin University


Parkinson’s disease (PD) is a neurodegenerative disorder associated with the misfolding and aggregation of α-synuclein in midbrain dopaminergic neurons. Familial PD is one of two forms of PD that accounts for 10% of all cases and is the result of genetic mutations. The best-studied gene, a-synuclein, has six known mutations. While the first identified mutants (A30P, E46K and A53T) are well studied, little is known about how recently discovered mutants (H50Q, G51D and A53E) create cellular toxicity. For my thesis, I utilized two yeast models to examine the hypothesis that H50Q, G51D, and A53E, each generate toxicity by affecting membrane-association and aggregation properties of a-synuclein. My research has revealed that: 1) All mutants alter a-synuclein’s cellular localization. 2) H50Q and A53E increase toxicity, but G51D does not. 3) None of the mutants affect a-synuclein concentration. This thesis provides new insight into familial PD pathogenesis potentially useful for novel therapeutic solutions.

Available for download on Monday, April 23, 2035