The PINK1 and parkin proteins jointly ensure quality control of mitochondria, the cell's powerhouse. Together they modify damaged mitochondria with phosphorylated ubiquitin (pS65-Ub), which appears to label the mitochondria for degradation. In some genetic forms of Parkinson's, PINK1 and parkin activity is lost, and mitochondrial dysfunction is seen in the broader Parkinson's population.
Given that pS65-Ub is a quantitative marker of mitochondrial damage, we hypothesize that pS65-Ub might be useful as a novel biomarker for Parkinson's disease.
In this proof-of-concept study, we aim to develop and optimize antibody-based assays to reliably quantify pS65-Ub from cells and different patient samples. We will determine the best assay conditions and antibody combinations, and assess their suitability as biomarkers for Parkinson's disease.
Impact on Diagnosis/Treatment of Parkinson's Disease:
Currently there are no biomarkers available for Parkinson's disease. However, these would be extremely valuable to diagnose and stratify patients as well as to the future development of therapies.
Next Steps for Development:
Upon successful development and optimization of the pS65-Ub assays and exploration of diverse patient specimens (cells, blood, cerebrospinal fluid) with limited sample numbers, next steps will include expansion to larger sample sizes of the respective specimens to establish pS65-Ub as a biomarker for Parkinson's.