{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:11:44Z","timestamp":1791288704787,"version":"4.3.0"},"reference-count":66,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007802","name":"Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica","doi-asserted-by":"publisher","award":["GPR17ALS"],"award-info":[{"award-number":["GPR17ALS"]}],"id":[{"id":"10.13039\/501100007802","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"publisher","award":["PSR2017"],"award-info":[{"award-number":["PSR2017"]}],"id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["Department of Excellence 2018-2022"],"award-info":[{"award-number":["Department of Excellence 2018-2022"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons (MN). Importantly, MN degeneration is intimately linked to oligodendrocyte dysfunction and impaired capacity of oligodendrocyte precursor cells (OPCs) to regenerate the myelin sheath enwrapping and protecting neuronal axons. Thus, improving OPC reparative abilities represents an innovative approach to counteract MN loss. A pivotal regulator of OPC maturation is the P2Y-like G protein-coupled receptor 17 (GPR17), whose role in ALS has never been investigated. In other models of neurodegeneration, an abnormal increase of GPR17 has been invariably associated to myelin defects and its pharmacological manipulation succeeded in restoring endogenous remyelination. Here, we analyzed GPR17 alterations in the SOD1G93A ALS mouse model and assessed in vitro whether this receptor could be targeted to correct oligodendrocyte alterations. Western-blot and immunohistochemical analyses showed that GPR17 protein levels are significantly increased in spinal cord of ALS mice at pre-symptomatic stage; this alteration is exacerbated at late symptomatic phases. Concomitantly, mature oligodendrocytes degenerate and are not successfully replaced. Moreover, OPCs isolated from spinal cord of SOD1G93A mice display defective differentiation compared to control cells, which is rescued by treatment with the GPR17 antagonist montelukast. These data open novel therapeutic perspectives for ALS management.<\/jats:p>","DOI":"10.3390\/ijms21072395","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T03:44:13Z","timestamp":1585712653000},"page":"2395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Abnormal Upregulation of GPR17 Receptor Contributes to Oligodendrocyte Dysfunction in SOD1 G93A Mice"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-9109","authenticated-orcid":false,"given":"Elisabetta","family":"Bonfanti","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Bonifacino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Center of Excellence for Biomedical Research (CEBR), University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2734-5418","authenticated-orcid":false,"given":"Stefano","family":"Raffaele","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3384-0666","authenticated-orcid":false,"given":"Marco","family":"Milanese","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Center of Excellence for Biomedical Research (CEBR), University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Morgante","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3744-5786","authenticated-orcid":false,"given":"Giambattista","family":"Bonanno","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Center of Excellence for Biomedical Research (CEBR), University of Genoa, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria P.","family":"Abbracchio","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-842X","authenticated-orcid":false,"given":"Marta","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/mus.21404","article-title":"Amyotrophic lateral sclerosis-evolutionary and other perspectives","volume":"40","author":"Eisen","year":"2009","journal-title":"Muscle Nerve"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jbior.2015.10.006","article-title":"SOD1 in neurotoxicity and its controversial roles in SOD1 mutation-negative ALS","volume":"60","author":"Hayashi","year":"2016","journal-title":"Adv. Biol. Regul."},{"key":"ref_3","first-page":"87","article-title":"White matter injury in amyotrophic lateral sclerosis (ALS)","volume":"34","author":"Dziewulska","year":"1996","journal-title":"Folia Neuropathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/nan.12555","article-title":"White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis","volume":"45","author":"Mollink","year":"2019","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/stem.2758","article-title":"Concise Review: The Cellular Conspiracy of Amyotrophic Lateral Sclerosis","volume":"36","author":"Serio","year":"2018","journal-title":"Stem Cells"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1126\/science.1123511","article-title":"Onset and progression in inherited ALS determined by motor neurons and microglia","volume":"312","author":"Yamanaka","year":"2006","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.stem.2008.09.017","article-title":"Human Embryonic Stem Cell-Derived Motor Neurons Are Sensitive to the Toxic Effect of Glial Cells Carrying an ALS-Causing Mutation","volume":"3","author":"Boulting","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nn2047","article-title":"Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis","volume":"11","author":"Yamanaka","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.neuron.2014.01.013","article-title":"Microglia induce motor neuron death via the classical NF-\u03baB pathway in amyotrophic lateral sclerosis","volume":"81","author":"Frakes","year":"2014","journal-title":"Neuron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/nature09614","article-title":"Myelination and support of axonal integrity by glia","volume":"468","author":"Nave","year":"2010","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature11314","article-title":"Oligodendroglia metabolically support axons and contribute to neurodegeneration","volume":"487","author":"Lee","year":"2012","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/nn.3357","article-title":"Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis","volume":"16","author":"Kang","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1093\/brain\/aws339","article-title":"Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis","volume":"136","author":"Philips","year":"2013","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E6496","DOI":"10.1073\/pnas.1607496113","article-title":"Oligodendrocytes contribute to motor neuron death in ALS via SOD1-dependent mechanism","volume":"113","author":"Ferraiuolo","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1002\/glia.23669","article-title":"Myelin degeneration induced by mutant superoxide dismutase 1 accumulation promotes amyotrophic lateral sclerosis","volume":"67","author":"Kim","year":"2019","journal-title":"Glia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e3579","DOI":"10.1371\/journal.pone.0003579","article-title":"The recently identified P2Y-like receptor GPR17 is a sensor of brain damage and a new target for brain repair","volume":"3","author":"Lecca","year":"2008","journal-title":"PLoS ONE"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1002\/glia.21237","article-title":"The GPR17 receptor in NG2 expressing cells: Focus on in vivocell maturation and participation in acute trauma and chronic damage","volume":"59","author":"Boda","year":"2011","journal-title":"Glia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10593","DOI":"10.1074\/jbc.M110.162867","article-title":"Phenotypic changes, signaling pathway, and functional correlates of GPR17-expressing neural precursor cells during oligodendrocyte differentiation","volume":"286","author":"Fumagalli","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1074\/jbc.M112.404996","article-title":"The regulated expression, intracellular trafficking, and membrane recycling of the P2Y-like receptor GPR17 in Oli-neu oligodendroglial cells","volume":"288","author":"Fratangeli","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1093\/brain\/awp147","article-title":"The P2Y-like receptor GPR17 as a sensor of damage and a new potential target in spinal cord injury","volume":"132","author":"Ceruti","year":"2009","journal-title":"Brain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s11302-013-9366-3","article-title":"Changes of the GPR17 receptor, a new target for neurorepair, in neurons and glial cells in patients with traumatic brain injury","volume":"9","author":"Franke","year":"2013","journal-title":"Purinergic Signal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.neuroscience.2011.11.066","article-title":"The new P2Y-like receptor G protein-coupled receptor 17 mediates acute neuronal injury and late microgliosis after focal cerebral ischemia in rats","volume":"202","author":"Zhao","year":"2012","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/glia.22929","article-title":"GPR17 expressing NG2-Glia: Oligodendrocyte progenitors serving as a reserve pool after injury","volume":"64","author":"Schneider","year":"2016","journal-title":"Glia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e2871","DOI":"10.1038\/cddis.2017.256","article-title":"The role of oligodendrocyte precursor cells expressing the GPR17 receptor in brain remodeling after stroke","volume":"8","author":"Bonfanti","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1002\/glia.23305","article-title":"Differential local tissue permissiveness influences the final fate of GPR17-expressing oligodendrocyte precursors in two distinct models of demyelination","volume":"66","author":"Coppolino","year":"2018","journal-title":"Glia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1002\/glia.22896","article-title":"The ubiquitin ligase Mdm2 controls oligodendrocyte maturation by intertwining mTOR with G protein-coupled receptor kinase 2 in the regulation of GPR17 receptor desensitization","volume":"63","author":"Fumagalli","year":"2015","journal-title":"Glia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1038\/nn.2410","article-title":"The oligodendrocyte-specific G protein-coupled receptor GPR17 is a cell-intrinsic timer of myelination","volume":"12","author":"Chen","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/5584_2017_92","article-title":"Pharmacological properties and biological functions of the GPR17 receptor, a potential target for neuro-regenerative medicine","volume":"Volume 1051","author":"Fumagalli","year":"2017","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1038\/sj.emboj.7601341","article-title":"The orphan receptor GPR17 identified as a new dual uracil nucleotides\/cysteinyl-leukotrienes receptor","volume":"25","author":"Ciana","year":"2006","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.phrs.2019.02.025","article-title":"Improvement of fiber connectivity and functional recovery after stroke by montelukast, an available and safe anti-asthmatic drug","volume":"142","author":"Gelosa","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10560","DOI":"10.1523\/JNEUROSCI.0898-16.2016","article-title":"Olig2-targeted G-protein-coupled receptor Gpr17 regulates oligodendrocyte survival in response to lysolecithin-induced demyelination","volume":"36","author":"Ou","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.neuropharm.2015.10.005","article-title":"CNS remyelination as a novel reparative approach to neurodegenerative diseases: The roles of purinergic signaling and the P2Y-like receptor GPR17","volume":"104","author":"Fumagalli","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1074\/jbc.M109.031674","article-title":"Adaptive modifications in the calpain\/calpastatin system in brain cells after persistent alteration in Ca2+ homeostasis","volume":"285","author":"Stifanese","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1111\/j.1471-4159.2010.07155.x","article-title":"Abnormal exocytotic release of glutamate in a mouse model of amyotrophic lateral sclerosis","volume":"116","author":"Milanese","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2014.08.006","article-title":"Role of calpain-1 in the early phase of experimental ALS","volume":"562","author":"Stifanese","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.celrep.2016.03.069","article-title":"Developmental Origin of Oligodendrocyte Lineage Cells Determines Response to Demyelination and Susceptibility to Age-Associated Functional Decline","volume":"15","author":"Crawford","year":"2016","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"a020453","DOI":"10.1101\/cshperspect.a020453","article-title":"Oligodendrocyte development and plasticity","volume":"8","author":"Bergles","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1083\/jcb.200501085","article-title":"A mutation in dynein rescues axonal transport defects and extends the life span of ALS mice","volume":"169","author":"Kieran","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"C1028","DOI":"10.1152\/ajpcell.00658.2008","article-title":"Functional characterization of two isoforms of the P2Y-like receptor GPR17: [35S]GTP\u03b3S binding and electrophysiological studies in 1321N1 cells","volume":"297","author":"Pugliese","year":"2009","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1021\/ml400399f","article-title":"Development of [3H]2-carboxy-4,6-dichloro-1 H -indole-3-propionic acid ([3H]PSB-12150): A useful tool for studying GPR17","volume":"5","author":"Ritter","year":"2014","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-11119-7","article-title":"Cyfip1 haploinsufficient rats show white matter changes, myelin thinning, abnormal oligodendrocytes and behavioural inflexibility","volume":"10","author":"Silva","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.neuropharm.2015.10.026","article-title":"Purinergic contribution to amyotrophic lateral sclerosis","volume":"104","author":"Apolloni","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11302-018-9633-4","article-title":"Purinergic implication in amyotrophic lateral sclerosis\u2014From pathological mechanisms to therapeutic perspectives","volume":"15","author":"Roszek","year":"2019","journal-title":"Purinergic Signal."},{"key":"ref_44","first-page":"1","article-title":"Regulation and signaling of the GPR17 receptor in oligodendroglial cells","volume":"2","author":"Lecca","year":"2020","journal-title":"Glia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/nn.3390","article-title":"Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain","volume":"16","author":"Hughes","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.neuropharm.2017.06.020","article-title":"In-vivo effects of knocking-down metabotropic glutamate receptor 5 in the SOD1G93A mouse model of amyotrophic lateral sclerosis","volume":"123","author":"Bonifacino","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.brainres.2011.06.033","article-title":"Evolution of gait abnormalities in SOD1 G93A transgenic mice","volume":"1406","author":"Mancuso","year":"2011","journal-title":"Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/brb3.143","article-title":"Characterization of early pathogenesis in the SOD1G93A mouse model of ALS: Part I, background and methods","volume":"3","author":"Vinsant","year":"2013","journal-title":"Brain Behav."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1152\/jn.00665.2003","article-title":"Hyperexcitability of Cultured Spinal Motoneurons from Presymptomatic ALS Mice","volume":"91","author":"Kuo","year":"2004","journal-title":"J. Neurophysiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/4553","article-title":"Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons","volume":"2","author":"Williamson","year":"1999","journal-title":"Nat. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1111\/j.1460-9568.2004.03745.x","article-title":"Altered sensorimotor development in a transgenic mouse model of amyotrophic lateral sclerosis","volume":"20","author":"Amendola","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10864","DOI":"10.1523\/JNEUROSCI.1340-08.2008","article-title":"Neonatal neuronal circuitry shows hyperexcitable disturbance in a mouse model of the adult-onset neurodegenerative disease amyotrophic lateral sclerosis","volume":"28","author":"Peuscher","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/brb3.142","article-title":"Characterization of early pathogenesis in the SOD1G93A mouse model of ALS: Part II, results and discussion","volume":"3","author":"Vinsant","year":"2013","journal-title":"Brain Behav."},{"key":"ref_54","first-page":"155","article-title":"Neurite Orientation Dispersion and Density Imaging Can Detect Presymptomatic Axonal Degeneration in The Spinal Cord of ALS Mice","volume":"33","author":"Gatto","year":"2018","journal-title":"Funct. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1016\/j.cub.2015.07.056","article-title":"CNS Myelin Sheath Lengths Are an Intrinsic Property of Oligodendrocytes","volume":"25","author":"Bechler","year":"2015","journal-title":"Curr. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1111\/j.1476-5381.2009.00633.x","article-title":"Distinct expression and ligand-binding profiles of two constitutively active GPR17 splice variants","volume":"159","author":"Rosenkilde","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s11302-011-9245-8","article-title":"Innovative functional cAMP assay for studying G protein-coupled receptors: Application to the pharmacological characterization of GPR17","volume":"7","author":"Buccioni","year":"2011","journal-title":"Purinergic Signal."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1002\/glia.22506","article-title":"UDP-glucose enhances outward K + currents necessary for cell differentiation and stimulates cell migration by activating the GPR17 receptor in oligodendrocyte precursors","volume":"61","author":"Coppi","year":"2013","journal-title":"Glia"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1124\/jpet.110.178715","article-title":"Agonist-induced desensitization\/resensitization of human G protein-coupled receptor 17: A functional cross-talk between purinergic and cysteinyl-leukotriene ligands","volume":"338","author":"Daniele","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"ra93","DOI":"10.1126\/scisignal.2004350","article-title":"Decoding signaling and function of the orphan g protein-coupled receptor GPR17 with a small-molecule agonist","volume":"6","author":"Hennen","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11685","DOI":"10.1073\/pnas.0905364106","article-title":"GPR17 is a negative regulator of the cysteinyl leukotriene 1 receptor response to leukotriene D4","volume":"106","author":"Maekawa","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.chembiol.2018.03.012","article-title":"Repurposing HAMI3379 to Block GPR17 and Promote Rodent and Human Oligodendrocyte Differentiation","volume":"25","author":"Merten","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Parravicini, C., Abbracchio, M.P., Fantucci, P., and Ranghino, G. (2010). Forced unbinding of GPR17 ligands from wild type and R255I mutant receptor models through a computational approach. BMC Struct. Biol., 10.","DOI":"10.1186\/1472-6807-10-8"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1124\/jpet.113.207647","article-title":"Is GPR17 a P2Y\/leukotriene receptor? examination of uracil nucleotides, nucleotide sugars, and cysteinyl leukotrienes as agonists of GPR17","volume":"347","author":"Qi","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms9466","article-title":"Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug","volume":"6","author":"Marschallinger","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1126\/science.8209258","article-title":"Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation","volume":"264","author":"Gurney","year":"1994","journal-title":"Science"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/7\/2395\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:13:39Z","timestamp":1760174019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/7\/2395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,31]]},"references-count":66,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["ijms21072395"],"URL":"https:\/\/doi.org\/10.3390\/ijms21072395","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,31]]}}}