1. Ecto-GPR37: a potential biomarker for Parkinson’s disease
- Author
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Víctor Fernández-Dueñas, Ulla E. Petäjä-Repo, Franc Llorens, Per Svenningsson, Eduard Sabidó, Wojciech Paslawski, Xavier Morató, Eva Borràs, Francisco Ciruela, Isidro Ferrer, Josep Argerich, Paula Garcia-Esparcia, and Inga Zerr
- Subjects
0301 basic medicine ,Male ,Parkinson's disease ,Neurology ,genetics [Alzheimer Disease] ,lcsh:RC346-429 ,Receptors, G-Protein-Coupled ,0302 clinical medicine ,Cerebrospinal fluid ,Malaltia de Parkinson ,Receptor ,Orphan receptor ,α-Synuclein ,Aged, 80 and over ,medicine.diagnostic_test ,Biochemical markers ,analysis [Receptors, G-Protein-Coupled] ,Parkinson Disease ,Middle Aged ,3. Good health ,Up-Regulation ,cerebrospinal fluid [Alzheimer Disease] ,Substantia Nigra ,Marcadors bioquímics ,alpha-Synuclein ,Biomarker (medicine) ,GPR37 ,Female ,diagnosis [Parkinson Disease] ,Alzheimer’s disease ,biosynthesis [Receptors, G-Protein-Coupled] ,medicine.medical_specialty ,Cognitive Neuroscience ,Substantia nigra ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Alzheimer Disease ,ddc:570 ,Internal medicine ,metabolism [Substantia Nigra] ,medicine ,Humans ,RNA, Messenger ,Parkinson, Malaltia de ,lcsh:Neurology. Diseases of the nervous system ,Aged ,Brain Chemistry ,genetics [Receptors, G-Protein-Coupled] ,biosynthesis [RNA, Messenger] ,business.industry ,Research ,Pael-R ,Reproducibility of Results ,Biomarker ,medicine.disease ,030104 developmental biology ,Endocrinology ,Immunoassay ,Parkinson’s disease ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Biomarkers ,cerebrospinal fluid [alpha-Synuclein] - Abstract
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. 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. 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
- Published
- 2021