Parkin removes damaged mitochondria, which protects neurons from cell death. However, in a form of familial PD, parkin haploinsufficiency cannot fully support neuronal survival. With funding in part from the Michael J. Fox Foundation and using a genome-edited neuronal cell line to monitor the endogenous levels of Parkin, we conducted a qHTS to identify transcriptional enhancers of the parkin locus. In a second strategy, we are employing a Caenorhabditis elegans (C. elegans) PD phenolog based on human PD-linked gene mutations in alpha-synuclein and the leucine-rich repeat kinase 2 (LRRK2). Using laser scanning cytometry methods, we are developing a 384-well qHTS-compatible C. elegans PD model system for evaluating libraries of investigational agents and approved drugs for their ability to inhibit nematode neurodegeneration.