Study Rationale: Mutations in the genes encoding PRKN and PINK1 are associated with Parkinson’s disease (PD). PINK1 and PPKN proteins work together to mediate the degradation of damaged mitochondria via a process called mitophagy; how changes in the amount of PRKN might affect the process is less clear. Currently, there are no sensitive methods to reliably quantify PRKN protein levels. Developing such a tool will be essential for understanding how mitophagy contributes to PD and for assessing the efficacy of future therapeutics.
Hypothesis: We hypothesize that developing a method for reliably measuring PRKN protein levels will be useful for studying the role of mitophagy in PD.
Study Design: We will assess different PRKN antibody pairs for their ability to sensitively measure PRKN protein levels in samples using a method called a sandwich ELISA. We will use samples from human and mouse origin that contain different amounts of PRKN, including some samples that have none. Once we have established the most effective antibody pairs, we will further optimize the assay and then start measuring PPKN in preclinical and postmortem samples.
Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, this method would facilitate assessment of PPKN levels in preclinical models and people with PD, a measurement that will help to determine the role of mitophagy in PD. PRKN levels will also be an important surrogate for treatments that might become available in the future.
Next Steps for Development: A sensitive and reliable assay for PRKN can be shared with the research community to answer important biological questions that ultimately contribute to the development of treatments for PD.