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

Translational Neurodegeneration

Inga Zerr¹  Paula Garcia-Esparcia²  Isidro Ferrer²  Franc Llorens³  Francisco Ciruela⁴  Josep Argerich⁴  Víctor Fernández-Dueñas⁴  Xavier Morató⁵  Eduard Sabidó⁶  Eva Borràs⁶  Ulla E. Petäjä-Repo⁷  Per Svenningsson⁸  Wojciech Paslawski⁸ 

[1] Department of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical School, Göttingen, Germany;German Center for Neurodegenerative Diseases, Göttingen, Germany;Neuroscience Program, Bellvitge Biomedical Research Institute, IDIBELL, L’Hospitalet de Llobregat, Spain;Neuropathology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L’Hospitalet de Llobregat, Spain;CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto Carlos III, Madrid, Spain;Neuroscience Program, Bellvitge Biomedical Research Institute, IDIBELL, L’Hospitalet de Llobregat, Spain;Neuropathology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L’Hospitalet de Llobregat, Spain;CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto Carlos III, Madrid, Spain;Department of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical School, Göttingen, Germany;Pharmacology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L’Hospitalet de Llobregat, Spain;Neuroscience Program, Bellvitge Biomedical Research Institute, IDIBELL, L’Hospitalet de Llobregat, Spain;Pharmacology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L’Hospitalet de Llobregat, Spain;Neuroscience Program, Bellvitge Biomedical Research Institute, IDIBELL, L’Hospitalet de Llobregat, Spain;Section of Neurology, Department of Clinical Neuroscience, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden;Proteomics Unit, Center for Genomic Regulation, Barcelona, Spain;Proteomics Unit, Universitat Pompeu Fabra, Barcelona, Spain;Research Unit of Biomedicine, Medical Research Center Oulu, University of Oulu, Oulu, Finland;Section of Neurology, Department of Clinical Neuroscience, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden;

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

DOI  :  10.1186/s40035-021-00232-7

来源: Springer

【 摘 要 】

Objectiveα-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.MethodsGPR37 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.ResultsGPR37 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.ConclusionGPR37 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】

CC BY