Expression and Characterization Studies of a-Synuclein to Model Parkinson\u27s Disease in Yeast

Parkinson’s disease (PD) is a fatal, incurable, neurodegenerative disease that affects approximately 4 million people worldwide. In this disease, dopaminergic neurons selectively die causing symptoms of postural rigidity, slowed motor movement, and resting tremors. Recently, the α-synuclein gene has been linked to both familial and sporadic forms of PD. α-Synuclein protein misfolds, aggregates and ultimately leads to cell death in dopaminergic neurons, but molecular mechanisms that cause misfolding and cell death are not fully understood. α-Synuclein overexpression causes PD-like pathology and symptoms in fruit flies and mice (two common model organisms). To date, no yeast model for PD has been reported. Given the present ability to genetically and biochemically manipulate yeast, we believe that this model system will facilitate understanding of α-synuclein misfolding and aggregation processes. This senior thesis project has four aims: to express α-synuclein in yeast, characterize its effect on yeast growth and metabolism, describe protein solubility, and characterize protein stability in yeast