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Clues from a missense mutation of the adenosine A1 receptor gene associated with early-onset Parkinson’s disease

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Neural Regeneration Research 2023年第10期18卷 2204-2205页

作者： Sergi Ferré Leonardo Pardo francisco ciruela Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Laboratory of Computational Medicine Biostatistics UnitFaculty of MedicineUniversitat Autònoma BarcelonaBellaterraBarcelonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of Barcelona.Neuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Parkinson’s disease (P D) is a com plex neu rodegenerative disorder for which ra re and common genetic variants contribute to disease risk,onset,and *** genetic contribution to PD can be classified mainly in,first,rare DNA variants that are highly penetrant and therefore causal,which are typically associated with monogenic PD;and second,more common risk polymorphic variants,which individually exert a small increase in the risk of the disease,which are usually identified in the most prevalent and apparently sporadic PD (Blauwendraat et al.,2020).

关键词： typically degenerative

G protein-coupled receptor 37(GPR37) emerges as an important modulator of adenosinergic transmission in the striatum

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Neural Regeneration Research 2019年第11期14卷 1912-1914页

作者： Xavier Morato Rodrigo A. Cunha francisco ciruela Unitat de Farmacologia Departament Patologia i Terapeutica ExperimentalFacultat de MedicinaInstituto de Investigacion Biomedica de Bellvitge (IDIBELL)Universitat de BarcelonaL’Hospitalet de LlobregatBarcelonaSpainInstitut de NeurocienciesUniversitat de BarcelonaBarcelonaSpain (Morato X Ciruela F) Center for Neuroscience and Cell Biology (CNC)-Center for Neurosciences and Cell BiologyUniversity of CoimbraCoimbraPortugalFaculty of MedicineUniversity of CoimbraCoimbraPortugal

G protein-coupled receptor 37 (GPR37), also known as parkin associated endothelin-like (Pael) receptor, is an orphan G protein- coupled receptor, which suffers a defective parking ubiquitination in autosomal recessive Parkinson’s disease promoting its endoplasmic reticulum aggregation and stress, neurotoxicity and neuronal death (Takahashi and Imai, 2003). Interestingly, we have demonstrated previously that GPR37 heteromerizes with adenosine A2A receptor (A2AR) in the striatum (Morato et al., 2017;Sokolina et al., 2017).

关键词： G protein-coupled receptor 37(GPR37) important modulator adenosinergic transmission

Dopaminergic-cholinergic imbalance in movement disorders: a role for the novel striatal dopamine D2-muscarinic acetylcholine M1 receptor heteromer

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Neural Regeneration Research 2021年第7期16卷 1406-1408页

作者： RenéA.J.Crans francisco ciruela Laboratory of Toxicology Department of BioanalysisGhent UniversityGhentBelgium Unitat de Farmacologia Departament Patologia i Terapèutica ExperimentalFacultat de Medicina i Ciències de la SalutIDIBELLUniversitat de BarcelonaL’Hospitalet de LlobregatBarcelonaSpain Institut de Neurociències Universitat de BarcelonaBarcelonaSpain

The striatum is the primary input structure of the basal ganglia, which participates in motivational and goaldirected behaviors(Pisani et al., 2007).In physiological conditions, local cholinergic interneurons(ChIs) an... 详细信息

关键词： al. Dopamine dopamine

Adenosine A2A-dopamine D2 receptor heteromers operate striatal function:impact on Parkinson's disease pharmacotherapeutics

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Neural Regeneration Research 2018年第2期13卷 241-243页

作者： víctor fernández-duenas sergi ferré francisco ciruela unitat de farmacologia departament patologia i terapèutica experimentalfacultat de medicinaidibelluniversitat de barcelonal’hospitalet de llobregatBarcelonaSpain institut de neurociències universitat de barcelonaBarcelonaSpain integrative neurobiology section national institute on drug abuseintramural research programnational institutes of healthBaltimoreMDUSA

The basal ganglia （BG） assemble a series of deep gray matter structures forming recurrent loops that include the cortex and thalamus, and that participate in the regulation of a plethora of brain functions, including elicitation and learning of reward-and aversive stimuli-associated behaviors, motor activity control and sensorimotor gating （Brom- berg-Martin et al., 2010）.

关键词： A(2A) RECEPTORS BASAL GANGLIA DOPAMINE-D-2

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

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Translational Neurodegeneration 2021年第1期10卷 77-90页

作者： Xavier Morato Paula Garcia-Esparcia Josep Argerich Franc Llorens Inga Zerr Wojciech Paslawski Eva Borras Eduard Sabido Ulla EPetaja-Repo Victor Fernandez-Duenas Isidro Ferrer Per Svenningsson francisco ciruela Pharm acology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaUHospitalet de LlobregatSpain Neuroscience Program Bellvitge Biomedical Research InstituteIDIBELLL'Hospitalet de LlobregatSpain Section of Neurology Department of Clinical NeuroscienceDepartm ent of NeuroscienceKarolinska InstituteStockholmSweden Neuropathology Unit Departm ent of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaL'Hospitalet de LlobregatSpain CIBERNED Centro de Investigacion Biomedica en Red de Enfermedades NeurodegenerativasInstituto CarlosⅢMadridSpain Department of Neurology Clinical Dementia Center and National Reference Center for CID SurveillanceUniversity Medical SchoolGottingenGermany German Center for Neurodegenerative Diseases GottingenGermany Proteomics Unit Center for Genomic RegulationBarcelonaSpain Proteomics Unit Universitat Pompeu FabraBarcelonaSpain Research Unit of Biomedicine Medical Research Center OuluUniversity of OuluOuluFinland

Objective:a-Synuclein has been studied as a potential biomarker for Parkinson's disease(PD)with no concluding ***,there is an urgent need to find out reliable specific biomarkers for ***37 is an orphan G protein-coupled receptor that toxically accumulates in autosomal recessive juvenile ***,we investigated whether GPR37 is upregulated in sporadic PD,and thus a suitable potential biomarker for ***:GPR37 protein density and mRNA expression in postmortem substantia nigra(SN)from PD patients were analysed by immunoblot and RT-qPCR,*** presence of peptides from the N-terminus-cleaved domain of GPR37(***-GPR37)in human cerebrospinal fluid(CSF)was determined by liquid chromatography-mass spectrometric *** 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)***:GPR37 protein density and mRNA expression were significantly augmented in sporadic *** amounts of ecto-GPR37 peptides in the CSF samples from PD patients were identified by mass spectrometry and quantified by the in-house ELISA ***,the CSF total a-synuclein level in PD patients did not differ from that in NC ***,the cortical GPR37 mRNA expression and CSF ecto-GPR37 levels in AD patients were also ***:GPR37 expression is increased in SN of sporadic PD *** ecto-GPR37 peptides are significantly increased in the CSF of PD patients,but not in AD *** results open perspectives and encourage further clinical studies to confirm the validity and utility of ecto-GPR37 as a potential PD biomarker.

关键词： GPR37 Pael-R Parkinson's disease Cerebrospinal fluid Biomarker Alzheimer's disease a-5ynuclein Orphan receptor