Fluorescence-Based Assay Development To Screen Drugs Against Parkinson?s Disease

Parkinson?s disease (PD) involves the generation of dopaminergic (DA) neurons in the substantia nigra, causing tremor and motor impairment. Defects in PARK2 protein are the cause of Parkinson?s disease type 2 (PARK2), also known as early-onset parkinsonism with diurnal fluctuation (EPDF) or autosomal recessive juvenile Parkinson?s disease (PDJ). In mouse model, Parkin is critical for removing dysfunctional mitochondria via autophagy. The absence of Parkin does not affect turnover under normal conditions. However, during stress conditions, Parkin helps to remove damaged mitochondria by autophagy. Innoprot has developed a novel fluorescence cell-based assay for High Content Screening to screen compounds that can promote Parkin2 mithocondrial localization without mitochondrial stress induction. In this work, we used this model to screen a library of 1200 compounds. After the screening campaign, the positive compounds were chosen for further testing, based on the strength of the initial response and the lack of cytotoxicity. Our results indicate that Parkin2 cell-based assay is a valid strategy for drug screening.