Journal
TRANSLATIONAL NEURODEGENERATION
Volume 10, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s40035-021-00232-7
Keywords
GPR37; Pael-R; Parkinson's disease; Cerebrospinal fluid; Biomarker; Alzheimer's disease; alpha-Synuclein; Orphan receptor
Categories
Funding
- Ministerio de Ciencia, Innovacion y Universidades-Agencia Estatal de Investigacion/FEDER [SAF2017-87349-R, MDM-2017-0729]
- ISCIII/FEDER [PIE14/00034, PI19/00144]
- Generalitat de Catalunya [2017SGR1604, 2017SGR595]
- Fundacio la Marato de TV3 [20152031]
- FWO [SBO-140028]
- ERC [Progsy 649116]
- Stiftelsen for Strategisk Forskning
- Wallenberg Clinical Scholarship
- PE I + D + i 2013-2016 from the Instituto de Salud Carlos III (ISCIII) [PT17/0019]
- ERDF
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The study shows that the expression of GPR37 is increased in the substantia nigra of sporadic PD patients, and elevated levels of ecto-GPR37 peptides were detected in the cerebrospinal fluid of PD patients.
Objective: alpha-Synuclein has been studied as a potential biomarker for Parkinson's disease (PD) with no concluding results. Accordingly, there is an urgent need to find out reliable specific biomarkers for PD. GPR37 is an orphan G protein-coupled receptor that toxically accumulates in autosomal recessive juvenile parkinsonism. Here, we investigated whether GPR37 is upregulated in sporadic PD, and thus a suitable potential biomarker for PD. Methods: GPR37 protein density and mRNA expression in postmortem substantia nigra (SN) from PD patients were analysed by immunoblot and RT-qPCR, respectively. The presence of peptides from the N-terminus-cleaved domain of GPR37 (i.e. ecto-GPR37) in human cerebrospinal fluid (CSF) was determined by liquid chromatography-mass spectrometric analysis. An engineered in-house nanoluciferase-based immunoassay was used to quantify ectoGPR37 in CSF samples from neurological control (NC) subjects, PD patients and Alzheimer's disease (AD) patients. Results: GPR37 protein density and mRNA expression were significantly augmented in sporadic PD. Increased amounts of ecto-GPR37 peptides in the CSF samples from PD patients were identified by mass spectrometry and quantified by the in-house ELISA method. However, the CSF total alpha-synuclein level in PD patients did not differ from that in NC subjects. Similarly, the cortical GPR37 mRNA expression and CSF ecto-GPR37 levels in AD patients were also unaltered. Conclusion: GPR37 expression is increased in SN of sporadic PD patients. The ecto-GPR37 peptides are significantly increased in the CSF of PD patients, but not in AD patients. These results open perspectives and encourage further clinical studies to confirm the validity and utility of ecto-GPR37 as a potential PD biomarker.
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