INVESTIGATOR: Nicanor Austriaco, Providence College
THEME: Neuroscience

ABSTRACT: Parkinson’s Disease (PD) is a neurodegenerative disorder that leads to progressive deterioration of motor function due to the loss of dopamine-producing cells in the brain. The pathological hallmark of PD is the abnormal aggregation of specific proteins, including, most significantly, α-synuclein, which is an abundant, presynaptic protein of 140 residues. There is also accumulation of another protein called tau in the form of neurofibrillary tangles. Over a decade ago, humanized yeast cells overexpressing human α-synuclein were shown to recapitulate several hallmark cellular characteristics of PD. Since then, these yeast cells have been used to characterize the dynamics of α-synuclein and tau aggregation, phosphorylation, and toxicity in the eukaryote. Last summer, studies in our laboratory revealed that the isothiocyanate, sulforaphane (SFN), appears to disrupt α- synuclein aggregation in yeast. In this RI-INBRE SURF proposal, we describe experiments to determine if SFN disrupts the interaction between α-synuclein and tau in a humanized yeast model of Parkinson’s Disease. Our hypothesis is that aggregates of α-synuclein and tau will co-localize in our yeast model of PD and that SFN would disrupt this colocalization. We anticipate that confirming this hypothesis would allow us to continue to test drugs known to disrupt α-synuclein aggregation to determine if their mechanism of action also alters tau behavior. This could reveal an innovative therapeutic strategy for the treatment of PD.

RELEVANCE: Parkinson’s Disease (PD) is a progressive disorder of the nervous system that is caused by the abnormal accumulation of two human proteins called α-synuclein and tau. Using yeast cells, we would like to determine if aggregates of both these proteins colocalize in yeast and if drugs known to disrupt α-synuclein aggregation would also disrupt this colocalization. Our hope is that this could reveal an innovative therapeutic strategy for the treatment of PD.