Xavier Morató1,2,3, Paula Garcia-Esparcia2,4,5, Josep Argerich1,2, Franc Llorens2,4,5,6, Inga Zerr6,7, Wojciech Paslawski3, Eva Borràs8,9, Eduard Sabidó8,9, Ulla E Petäjä-Repo10, Víctor Fernández-Dueñas1,2, Isidro Ferrer2,4,5, Per Svenningsson3, Francisco Ciruela11,12. 1. 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. 2. Neuroscience Program, Bellvitge Biomedical Research Institute, IDIBELL, L'Hospitalet de Llobregat, Spain. 3. Section of Neurology, Department of Clinical Neuroscience, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden. 4. 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. 5. CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto Carlos III, Madrid, Spain. 6. Department of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical School, Göttingen, Germany. 7. German Center for Neurodegenerative Diseases, Göttingen, Germany. 8. Proteomics Unit, Center for Genomic Regulation, Barcelona, Spain. 9. Proteomics Unit, Universitat Pompeu Fabra, Barcelona, Spain. 10. Research Unit of Biomedicine, Medical Research Center Oulu, University of Oulu, Oulu, Finland. 11. 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. fciruela@ub.edu. 12. Neuroscience Program, Bellvitge Biomedical Research Institute, IDIBELL, L'Hospitalet de Llobregat, Spain. fciruela@ub.edu.
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.
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.
Authors: Ziad S Nasreddine; Natalie A Phillips; Valérie Bédirian; Simon Charbonneau; Victor Whitehead; Isabelle Collin; Jeffrey L Cummings; Howard Chertkow Journal: J Am Geriatr Soc Date: 2005-04 Impact factor: 5.562
Authors: H Shimura; N Hattori; S i Kubo; Y Mizuno; S Asakawa; S Minoshima; N Shimizu; K Iwai; T Chiba; K Tanaka; T Suzuki Journal: Nat Genet Date: 2000-07 Impact factor: 38.330
Authors: Lucilla Parnetti; Davide Chiasserini; Gianni Bellomo; David Giannandrea; Claudia De Carlo; Mohamed M Qureshi; Mustafa T Ardah; Shiji Varghese; Laura Bonanni; Barbara Borroni; Nicola Tambasco; Paolo Eusebi; Aroldo Rossi; Marco Onofrj; Alessandro Padovani; Paolo Calabresi; Omar El-Agnaf Journal: Mov Disord Date: 2011-04-05 Impact factor: 10.338