Funded Studies
Genetic research has provided new insight into the underlying causes of Parkinson's disease, but this has not yet resulted in any direct benefit to the patients. In particular, this has not lead to the discovery of any drugs which could slow down the disease process. One of the more recently discovered PD genes is DJ-1. We do not know how the abnormalities in this DJ-1 gene cause PD. We want to establish a DJ-1 deficient zebrafish model of PD. Zebrafish are a new animal model and are already frequently used for the study of other diseases. They are easy to keep, have a short generation span and breed well. The brain anatomy of zebrafish is easy to study since zebrafish embryos are transparent and zebrafish also have much fewer dopamine-producing nerve cells than humans. The maintenance costs for zebrafish is about 1/1000th of the maintenance costs for mice. We want to investigate three specific aims: 1) How similar is the distribution of cell death in DJ-1 deficient zebrafish and "classic" Lewy body PD? 2) Does DJ-1 deficiency lead to increased vulnerability to cell stressors such as oxidative stress and environmental toxins? 3) Does DJ-1 deficiency make other proteins such as alpha-synuclein or tau more toxic? Once we have answered all these questions, we will hopefully be able to use DJ-1-mutant zebrafish as a screening tool for new disease-modifying drugs in PD. In other areas, this has led to the identification of substances which correct a congenital heart abnormality.