Cerebrospinal fluid ecto-GPR37 in Parkinson’s disease

Improved diagnostic and prognostic biomarkers which reflect pathological progression would benefit the management of Parkinson’s disease. GPR37, also known as parkin associated endothelin-like (Pael) receptor, is an orphan G protein-coupled receptor, which has a defective parkin-mediated ubiquitination in autosomal recessive Parkinson’s disease. By means of immunoblot and mRNA determinations we detected increased GPR37 levels in postmortem substantia nigra from Parkinson’s disease subjects. We revealed the presence of the N-terminal domain of GPR37 (ecto-GPR37) in human and mouse cerebrospinal fluid (CSF). We engineered a Nanoluciferase-based ELISA to evaluate ecto-GPR37 in CSF and demonstrated the presence of ecto-GPR37 in CSF from wild-type, but not from GPR37-/-, mice. Subsequently, the relative abundance of ecto-GPR37 in CSF in healthy controls (n=48) and Parkinson’s disease (n=45) patients was assessed. Interestingly, we found that ecto-GPR37 was significantly increased (P = 0.0002) in the CSF from Parkinson’s disease patients. Importantly, mass spectrometric analysis of immunoprecipitation of GPR37 in CSF supported the analytical validity of our ELISA to measure ecto-GPR37 in human CSF. Overall, these results open exciting perspectives and encourage further systemically studies to confirm the clinical validity and utility of ecto-GPR37 as a potential Parkinson’s disease diagnostic/prognostic biomarker