Ecto-GPR37: a potential biomarker for Parkinson’s disease

Translational Neurodegeneration

Inga Zerr¹  Paula Garcia-Esparcia²  Franc Llorens²  Isidro Ferrer²  Xavier Morató³  Víctor Fernández-Dueñas³  Josep Argerich³  Francisco Ciruela³  Eduard Sabidó⁴  Eva Borràs⁴  Ulla E. Petäjä-Repo⁵  Wojciech Paslawski⁶  Per Svenningsson⁶ 

[1] Department of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical School;Neuroscience Program, Bellvitge Biomedical Research Institute, IDIBELL;Pharmacology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona;Proteomics Unit, Center for Genomic Regulation;Research Unit of Biomedicine, Medical Research Center Oulu, University of Oulu;Section of Neurology, Department of Clinical Neuroscience, Department of Neuroscience, Karolinska Institute;

关键词: GPR37;    Pael-R;    Parkinson’s disease;    Cerebrospinal fluid;    Biomarker;    Alzheimer’s disease;   

DOI  :  10.1186/s40035-021-00232-7

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown