Ecto-GPR37 : a potential biomarker for Parkinson’s disease
|Author:||Morató, Xavier1,2,3; Garcia-Esparcia, Paula2,4,5; Argerich, Josep1,2;|
1Pharmacology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L’Hospitalet de Llobregat, Spain
2Neuroscience Program, Bellvitge Biomedical Research Institute, IDIBELL, L’Hospitalet de Llobregat, Spain
3Section of Neurology, Department of Clinical Neuroscience, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden
4Neuropathology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L’Hospitalet de Llobregat, Spain
5CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto Carlos III, Madrid, Spain
6Department of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical School, Göttingen, Germany
7German Center for Neurodegenerative Diseases, Göttingen, Germany
8Proteomics Unit, Center for Genomic Regulation, Barcelona, Spain
9Proteomics Unit, Universitat Pompeu Fabra, Barcelona, Spain
10Research Unit of Biomedicine, Medical Research Center Oulu, University of Oulu, Oulu, Finland
|Online Access:||PDF Full Text (PDF, 1.7 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe202103319158
|Publish Date:|| 2021-03-31
Objective: α-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 ecto-GPR37 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 α-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.
Conclusions: 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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
318 Medical biotechnology
This work was supported by Ministerio de Ciencia, Innovación y Universidades–Agencia Estatal de Investigación/FEDER (SAF2017–87349-R and MDM-2017-0729) and ISCIII/FEDER (PIE14/00034 and PI19/00144), Generalitat de Catalunya (2017SGR1604, 2017SGR595), Fundació la Marató de TV3 (Grant 20152031) and FWO (SBO-140028). ERC consolidator grant (Progsy 649116), Stiftelsen för Strategisk Forskning and a Wallenberg Clinical Scholarship to PS. The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I + D + i 2013–2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF.
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