Over a million Americans have Parkinson’s disease (PD) or related disorders such as progressive supranuclear palsy (PSP). These diseases are characterized by relentlessly worsening motor and cognitive function, caused by degeneration of nerve cells in the brain. No currently available medication slows or arrests disease progression. Even symptomatic treatments show declining usefulness in advanced PD and are often ineffective in PSP. There is an urgent and unmet need for effective treatments for these diseases.
Our work is focused on understanding the mechanisms underlying neurodegeneration in PD and PSP, as an essential step towards developing effective treatments. Our current projects focus on the roles of the proteins alpha-synuclein and tau in the populations of brain neurons that selectively degenerate in these diseases. To understand how accumulation of alpha-synuclein and tau causes neurodegeneration, we use a variety of different experimental models and approaches, including engineered viral vectors that alter gene expression in the rodent brain, and transgenic zebrafish that can be analyzed by intravital microscopy, electrophysiology, genetics and biochemistry. We are also exploring unbiased phenotype-based chemical modifier screens in zebrafish models for drug discovery. The ultimate goal of this work is to develop treatments that prevent the progression of PD and PSP.