{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T20:39:00Z","timestamp":1771533540010,"version":"3.50.1"},"reference-count":108,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["420695\/2018-4"],"award-info":[{"award-number":["420695\/2018-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["304450\/2019-7"],"award-info":[{"award-number":["304450\/2019-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004263","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul","doi-asserted-by":"publisher","award":["17\/2551-0000977-0"],"award-info":[{"award-number":["17\/2551-0000977-0"]}],"id":[{"id":"10.13039\/501100004263","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Huntington\u2019s disease (HD) is a devastating, progressive, and fatal neurodegenerative disorder inherited in an autosomal dominant manner. This condition is characterized by motor dysfunction (chorea in the early stage, followed by bradykinesia, dystonia, and motor incoordination in the late stage), psychiatric disturbance, and cognitive decline. The neuropathological hallmark of HD is the pronounced neuronal loss in the striatum (caudate nucleus and putamen). The striatum is related to the movement control, flexibility, motivation, and learning and the purinergic signaling has an important role in the control of these events. Purinergic signaling involves the actions of purine nucleotides and nucleosides through the activation of P2 and P1 receptors, respectively. Extracellular nucleotide and nucleoside-metabolizing enzymes control the levels of these messengers, modulating the purinergic signaling. The striatum has a high expression of adenosine A<jats:sub>2A<\/jats:sub> receptors, which are involved in the neurodegeneration observed in HD. The P2X7 and P2Y2 receptors may also play a role in the pathophysiology of HD. Interestingly, nucleotide and nucleoside levels may be altered in HD animal models and humans with HD. This review presents several studies describing the relationship between purinergic signaling and HD, as well as the use of purinoceptors as pharmacological targets and biomarkers for this neurodegenerative disorder.<\/jats:p>","DOI":"10.3389\/fnins.2021.657338","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T13:39:32Z","timestamp":1625146772000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Purinergic Signaling in the Pathophysiology and Treatment of Huntington\u2019s Disease"],"prefix":"10.3389","volume":"15","author":[{"given":"Melissa Talita","family":"Wiprich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla Denise","family":"Bonan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/0163-7258(94)00048-4","article-title":"Purinoceptors: are there families of P2X and P2Y purinoceptors?","volume":"64","author":"Abbracchio","year":"1994","journal-title":"Pharmacol. Ther."},{"key":"B2","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/0166-2236(89)90074-X","article-title":"The functional anatomy of basal ganglia disorders.","volume":"12","author":"Albin","year":"1989","journal-title":"Trends. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"10982","DOI":"10.1523\/JNEUROSCI.23-34-10982-2003","article-title":"Adenosinergic protection of dopaminergic and GABAergic neurons against mitochondrial inhibition through receptors located in the substantia nigra and striatum, respectively.","volume":"23","author":"Alfinito","year":"2003","journal-title":"J. Neurosci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"331","DOI":"10.2217\/nmt-2016-0008","article-title":"The global prevalence of Huntington\u2019s disease: a systematic review and discussion.","volume":"6","author":"Baig","year":"2016","journal-title":"Neurodegener. Dis. Manag."},{"key":"B5","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/978-3-319-60192-2_9","article-title":"Using genome engineering to understand huntington\u2019s disease","author":"Bailus","year":"2017","journal-title":"Genome Editing in Neurosciences"},{"key":"B6","doi-asserted-by":"publisher","first-page":"15005","DOI":"10.1038\/nrdp.2015.5","article-title":"Huntington disease.","volume":"1","author":"Bates","year":"2015","journal-title":"Nat. Rev. Dis. Primers."},{"key":"B7","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1111\/j.1447.4159.2005.03169.x","article-title":"Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington\u2019s disease mutation.","volume":"94","author":"Bauer","year":"2005","journal-title":"J. Neurochem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.neuroscience.2007.03.010","article-title":"Glutamate receptor abnormalities in the YAC128 transgenic mouse model of huntington\u2019s disease.","volume":"147","author":"Benn","year":"2007","journal-title":"Neuroscience"},{"key":"B9","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1089\/caff.2018.0006","article-title":"The role of adenosine tone and adenosine receptors in huntington\u2019s disease.","volume":"8","author":"Blum","year":"2018","journal-title":"J. Caffeine. Adenosine. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"9122","DOI":"10.1523\/JNEUROSCI.22.20.09122.2002","article-title":"The adenosine A1 receptor agonist adenosine amine congener exerts a neuroprotective effect against the development of striatal lesions and motor impairments in the 3-nitropropionic acid model of neurotoxicity.","volume":"22","author":"Blum","year":"2002","journal-title":"J. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3389\/fnins.2020.00082","article-title":"Cortical and striatal circuits in huntington\u2019s disease.","volume":"14","author":"Blumenstock","year":"2020","journal-title":"Front. Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"739","DOI":"10.2174\/187152712803581092","article-title":"Ectonucleotidases and nucleotide\/nucleoside transporters as pharmacological targets for neurological disorders.","volume":"11","author":"Bonan","year":"2012","journal-title":"CNS. Neurol. Disord. Drug. Targets."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1152\/physrev.00049.2017","article-title":"Pharmacology of adenosine receptors: the state of the art.","volume":"98","author":"Borea","year":"2018","journal-title":"Physiol. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1007\/s11011-017-0086-1","article-title":"Selective A2A receptor antagonist SCH 58261 modulates striatal oxidative stress and alleviates toxicity induced by 3-Nitropropionic acid in male Wistar rats.","volume":"32","author":"Bortolatto","year":"2017","journal-title":"Metab. Brain. Dis."},{"key":"B15","first-page":"509","article-title":"Purinergic nerves.","volume":"24","author":"Burnstock","year":"1972","journal-title":"Pharmacol. Rev."},{"key":"B16","first-page":"141","article-title":"Purinergic nerves and receptors.","volume":"16","author":"Burnstock","year":"1980","journal-title":"Prog. Biochem. Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/nrd2605","article-title":"Purinergic signalling and disorders of the central nervous system.","volume":"7","author":"Burnstock","year":"2008","journal-title":"Nat. Rev. Drug. Discov."},{"key":"B18","doi-asserted-by":"publisher","first-page":"973","DOI":"10.2174\/156802611795347627","article-title":"Adenosine and ATP receptors in the brain.","volume":"11","author":"Burnstock","year":"2011","journal-title":"Curr. Top. Med. Chem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.4103\/1673-5374.165300","article-title":"Purinergic signalling in neuroregeneration.","volume":"10","author":"Burnstock","year":"2015","journal-title":"Neural. Regn. Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2398212818817494","DOI":"10.1177\/2398212818817494","article-title":"Purine and purinergic receptors.","volume":"2","author":"Burnstock","year":"2018","journal-title":"Brain. Neurosci. Adv."},{"key":"B21","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1007\/s10072-019-04177-8","article-title":"Late-onset huntington\u2019s disease with 40\u201342 CAG expansion.","volume":"41","author":"Capiluppi","year":"2020","journal-title":"Neurol. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/978-3-319-71779-1_3","article-title":"Mitochondrial dysfunction in huntington\u2019s disease.","volume":"1049","author":"Carmo","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1098\/rstb.1999.0449","article-title":"Altered neurotransmitter receptor expression in transgenic mouse models of Huntington\u2019s disease.","volume":"354","author":"Cha","year":"1999","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1093\/hmg\/11.17.1939","article-title":"Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington\u2019s disease.","volume":"11","author":"Chan","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/mp.2017.188","article-title":"Purinergic system in psychiatric diseases.","volume":"23","author":"Cheffer","year":"2018","journal-title":"Mol. Psychiatry."},{"key":"B26","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/978-3-642-13443-2_10","article-title":"Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies.","volume":"200","author":"Chen","year":"2011","journal-title":"Handb. Exp. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2929","DOI":"10.1093\/hmg\/ddp230","article-title":"The A2A adenosine receptor rescues the urea cycle deficiency of Huntington\u2019s disease by enhancing the activity of the ubiquitin-proteasome system.","volume":"18","author":"Chiang","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"B28","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1111\/j.1471.4159.2005.03029.x","article-title":"CGS21680 attenuates symptoms of huntington\u2019s disease in a transgenic mouse model.","volume":"93","author":"Chou","year":"2005","journal-title":"J. Neurochem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11302-018-9633-4","article-title":"Purinergic implication in amyotrophic lateral sclerosis- from pathological mechanisms to therapeutic perspectives.","volume":"15","author":"Cieslak","year":"2019","journal-title":"Purinergic. Signal"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.3390\/ijms21061997","article-title":"Special issue: G protein-coupled adenosine receptors: molecular aspects and beyond.","volume":"21","author":"Ciruela","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.neuropharm.2015.04.001","article-title":"Lighting up G protein-coupled purinergic receptors with engineered fluorescent ligands.","volume":"98","author":"Ciruela","year":"2015","journal-title":"Neuropharmacology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s40265-016-0670-4","article-title":"Current pharmacological approaches to reduce chorea in huntington\u2019s disease.","volume":"77","author":"Coppen","year":"2017","journal-title":"Drugs."},{"key":"B33","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3389\/fnins.2020.00073","article-title":"Uric acid as a potential peripheral biomarker for disease features in huntington\u2019s patients.","volume":"14","author":"Corey-Bloom","year":"2020","journal-title":"Front. Neurosci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.nbd.2018.08.010","article-title":"A role for autophagy in huntington\u2019s disease.","volume":"122","author":"Croce","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s11302-005-0649-1","article-title":"Neuroprotection by adenosine in the brain: From A(1) receptor activation to A(2A) receptor blockade.","volume":"1","author":"Cunha","year":"2005","journal-title":"Purinergic. Signal"},{"key":"B36","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3390\/molecules25030482","article-title":"Huntington\u2019s disease: a review of the known pet imaging biomarkers and targeting radiotracers.","volume":"25","author":"Cybulska","year":"2020","journal-title":"Molecules"},{"key":"B37","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.nbd.2009.06.009","article-title":"A genetic variation in the ADORA2A gene modifies age at onset in huntington\u2019s disease.","volume":"35","author":"Dhaenens","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1096\/fj.08.122275","article-title":"Altered P2X7-receptor level and function in mouse models of huntington\u2019s disease and therapeutic efficacy of antagonist administration.","volume":"23","author":"D\u00edaz-Hern\u00e1ndez","year":"2009","journal-title":"FASEB. J."},{"key":"B39","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s11302.018-0609-4","article-title":"Neuronal adenosine A2Areceptor overexpression is neuroprotective towards 3-nitropropionic acid-induced striatal toxicity: a rat model of huntington\u2019s disease.","volume":"14","author":"Domenici","year":"2018","journal-title":"Purinergic. Signal"},{"key":"B40","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.nbd.2007.07.009","article-title":"Behavioral and electrophysiological effects of the adenosine A2A receptor antagonist SCH 58261 in R6\/2 Huntington\u2019s disease mice.","volume":"28","author":"Domenici","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.nbd.2018.09.025","article-title":"Normalizing glucocorticoid levels attenuates metabolic and neuropathological symptoms in the R6\/2 mouse model of Huntington\u2019s disease.","volume":"121","author":"Dufour","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/jbrainres.2010.01.080","article-title":"Influence of CGS 21680, a selective adenosine A2A receptor agonist, on NMDA receptor function and expression in the brain of Huntington\u2019s disease mice.","volume":"1323","author":"Ferrante","year":"2010","journal-title":"Brain. Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.nbd.2014.08.013","article-title":"Expression, pharmacology and functional activity of adenosine A1 receptors in genetic models of Huntington\u2019s disease.","volume":"71","author":"Ferrante","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"B44","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1100\/tsw.2007.211","article-title":"Adenosine receptor heteromers and their integrative role in striatal function.","volume":"7","author":"Ferr\u00e9","year":"2007","journal-title":"Scientific. World. J."},{"key":"B45","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1046\/j.1471.4159.2003.02145.x","article-title":"Genetic and pharmacological inactivation of the adenosine A2A receptor attenuates 3-nitropropionic acid-induced striatal damage.","volume":"88","author":"Fink","year":"2004","journal-title":"J. Neurochem."},{"key":"B46","first-page":"527","article-title":"International Union of Pharmacology. XXV. nomenclature and classification of adenosine receptors.","volume":"53","author":"Fredholm","year":"2001","journal-title":"Pharmacol. Rev."},{"key":"B47","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.physbeh.2007.05.034","article-title":"Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function.","volume":"92","author":"Fuxe","year":"2007","journal-title":"Physiol. Behav."},{"key":"B48","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/s0006-8993(03)02942-1","article-title":"Adenosine A2A antagonism increases striatal glutamate outflow in the quinolinic acid rat model of Huntington\u2019s disease.","volume":"979","author":"Gianfriddo","year":"2003","journal-title":"Brain. Res."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0717-5","article-title":"ATP and spontaneous calcium oscillations control neural stem cell fate determination in Huntington\u2019s disease: a novel approach for cell clock research.","author":"Glaser","year":"2020","journal-title":"Mol. Psychiatry."},{"key":"B50","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/s0306-4522(00)00008-7","article-title":"The pattern of neurodegeneration in Huntington\u2019s disease: a comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington\u2019s disease.","volume":"97","author":"Glass","year":"2000","journal-title":"Neuroscience"},{"key":"B51","doi-asserted-by":"publisher","first-page":"R509","DOI":"10.1016\/s0960-9822(00)00593-5","article-title":"The basal ganglia.","volume":"10","author":"Graybiel","year":"2000","journal-title":"Curr. Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.nbd.2016.08.013","article-title":"Equilibrative nucleoside transporter ENT1 as a biomarker of Huntington disease.","volume":"96","author":"Guitart","year":"2016","journal-title":"Neurobiol Dis."},{"key":"B53","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1113\/jphysiol.2007.132618","article-title":"Adenosine modulates transmission at the hippocampal mossy fiber synapse via direct inhibition of presynaptic calcium channels.","volume":"582","author":"Gundlfinger","year":"2007","journal-title":"J. Physiol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1134\/S0006297918090043","article-title":"Molecular pathogenesis in Huntington\u2019s Disease.","volume":"83","author":"Illarioshkin","year":"2018","journal-title":"Biochemistry (Mosc.)"},{"key":"B55","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.physbeh.2015.12.015","article-title":"Spermidine ameliorates 3-nitropropionic acid (3-NP)- induced striatal toxicity: possible role of oxidative stress, neuroinflammation, and neurotransmitters.","volume":"155","author":"Jamwal","year":"2016","journal-title":"Physiol. Behav."},{"key":"B56","doi-asserted-by":"publisher","first-page":"165","DOI":"10.2174\/1570159X6666180302115032","article-title":"Insight into the emerging role of striatal neurotransmitters in the pathophysiology of Parkinson\u2019s disease and Huntington\u2019s disease: a review.","volume":"17","author":"Jamwal","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s12640-015-9535-y","article-title":"Protective effect of spermidine against excitotoxic neuronal death induced by quinolinic acid in rats: possible neurotransmitters and neuroinflammatory mechanisms.","volume":"28","author":"Jamwal","year":"2015","journal-title":"Neurotox. Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.mito.2017.12.002","article-title":"Succinate dehydrogenase: prospect for neurodegenerative diseases.","volume":"42","author":"Jodeiri Farshbaf","year":"2018","journal-title":"Mitochondrion"},{"key":"B59","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.freeradbiomed.2013.04.016","article-title":"PGC-1\u03b1, mitochondrial dysfunction, and Huntington\u2019s disease.","volume":"62","author":"Johri","year":"2013","journal-title":"Free. Radic. Biol. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1093\/hmg\/ddw402","article-title":"Targeting ENT1 and adenosine tone for the treatment of Huntington\u2019s disease.","volume":"26","author":"Kao","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"B61","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1002\/ana.410220318","article-title":"Elevated serotonin and reduced dopamine in subregionally divided Huntington\u2019s disease striatum.","volume":"22","author":"Kish","year":"1987","journal-title":"Ann. Neurol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1002\/jnr.24495","article-title":"Dysfunctional striatal dopamine signaling in Huntington\u2019s disease.","volume":"97","author":"Koch","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"B63","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1046\/j.1471-4159.2001.00607.x","article-title":"Adenosine in the central nervous system: release mechanisms and extracellular concentrations.","volume":"79","author":"Latini","year":"2001","journal-title":"J. Neurochem."},{"key":"B64","doi-asserted-by":"publisher","first-page":"422","DOI":"10.2174\/1570159X16666180416093717","article-title":"Functional cross-talk between adenosine and metabotropic glutamate receptors.","volume":"17","author":"Le\u00f3n-Navarro","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.nbd.2015.03.030","article-title":"Inactivation of adenosine A2A receptors reverses working memory deficits at early stages of Huntington\u2019s disease models.","volume":"79","author":"Li","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1016\/j.bbrc.2016.09.065","article-title":"Energy defects in Huntington\u2019s disease: Why \u201cin vivo\u201d evidence matters.","volume":"483","author":"Liot","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B67","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.neulet.2005.09.037","article-title":"The platelet maximum number of A2A-receptor binding sites (Bmax) linearly correlates with age at onset and CAG repeat expansion in Huntington\u2019s disease patients with predominant chorea.","volume":"393","author":"Maglione","year":"2006","journal-title":"Neurosci. Lett."},{"key":"B68","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1002\/ajmg.b.30223","article-title":"Adenosine A2A receptor dysfunction correlates with age at onset anticipation in blood platelets of subjects with Huntington\u2019s disease.","author":"Maglione","year":"2005","journal-title":"Am. J. Med. Genet. Neuropsychiatr. Genet."},{"key":"B69","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/0306-4522(91)90038-p","article-title":"Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease.","volume":"42","author":"Martinez-Mir","year":"1991","journal-title":"Neuroscience"},{"key":"B70","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.neulet.2007.02.034","article-title":"Opposite effects of the A2A receptor agonist CGS21680 in the striatum of Huntington\u2019s disease versus wild-type mice.","volume":"417","author":"Martire","year":"2007","journal-title":"Neurosci. Lett."},{"key":"B71","doi-asserted-by":"publisher","first-page":"633861","DOI":"10.3389\/fphar.2020.633861","article-title":"P2X7 receptor agonist 2\u2019(3\u2019)-O-(4-Benzoylbenzoyl)ATP differently modulates cell viability and coricostriatal synaptic transmission in experimental models of Huntington\u2019s disease.","volume":"19","author":"Martire","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1007\/s00259-014-2724-8","article-title":"Cross-sectional PET study of cerebral adenosine A1 receptors in premanifest and manifest Huntington\u2019s disease.","volume":"41","author":"Matusch","year":"2014","journal-title":"Eur. J. Nucl. Med. Mol. Imaging."},{"key":"B73","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3389\/fphys.2017.00127","article-title":"Transcriptional signature of an altered purine metabolism in the skeletal muscle of a Huntington\u2019s disease mouse model.","volume":"8","author":"Mielcarek","year":"2017","journal-title":"Front. Physio."},{"key":"B74","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.nbd.2010.09.021","article-title":"A2A receptor knockout worsens survival and motor behavior in a transgenic mouse model of Huntington\u2019s disease.","volume":"41","author":"Mievis","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"B75","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1097\/nen.0b013e3180517477","article-title":"Effects of the adenosine A2A receptor antagonist SCH 58621 on cyclooxygenase-2 expression, glial activation, and brain-derived neurotrophic factor availability in a rat model of striatal neurodegeneration.","volume":"66","author":"Minghetti","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1016\/j.pharep.2014.07.006","article-title":"Improvement of mitochondrial NAD+\/FAD+-linked state-3 respiration by caffeine attenuates quinolinic acid-induced motor impairment in rats: implications in Huntington\u2019s disease.","volume":"66","author":"Mishra","year":"2014","journal-title":"Pharmacol. Rep."},{"key":"B77","doi-asserted-by":"publisher","first-page":"567430","DOI":"10.3389\/fnmol.2020.567430","article-title":"P2X7 receptor upregulation in Huntington\u2019s disease brains.","volume":"6","author":"Oll\u00e0","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"B78","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/B978-0-444-64012-3.00010-1","article-title":"The psychopharmacology of Huntington disease.","volume":"165","author":"Peters\u00e9n","year":"2019","journal-title":"Handb. Clin. Neurol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1523\/JNEUROOSCI.22-05-01967.2002","article-title":"Blockade of striatal adenosine A2A receptor reduces, through a presynaptic mechanism, quinolinic acid-induced excitotoxicity: possible relevance to neuroprotective interventions in neurodegenerative diseases of the striatum.","volume":"22","author":"Popoli","year":"2002","journal-title":"J. Neurosci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/s11302-007-9066-y","article-title":"Adenosine A2A receptors modulate BDNF both in normal conditions and in experimental models of Huntington\u2019s disease.","volume":"3","author":"Potenza","year":"2007","journal-title":"Purinergic. Signal."},{"key":"B81","doi-asserted-by":"publisher","first-page":"23672","DOI":"10.3390\/ijms151223672","article-title":"P2X and P2Y receptors\u2014role in the pathophysiology of the nervous system.","volume":"15","author":"Pucha\u0142owicz","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"B82","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1007\/s12640-019-00087-x","article-title":"Quality control in Huntington\u2019s disease: a therapeutic target.","volume":"36","author":"Rai","year":"2019","journal-title":"Neurotox. Res."},{"key":"B83","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1093\/ilar.48.4.356","article-title":"Animal models of Huntington\u2019s Disease.","volume":"48","author":"Ramaswamy","year":"2007","journal-title":"ILAR. J."},{"key":"B84","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/neuropharm.2015.11.006","article-title":"Purine nucleosides in neuroregeneration and neuroprotection.","volume":"104","author":"Ribeiro","year":"2016","journal-title":"Neuropharmacology"},{"key":"B85","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1097\/00001756-199410270-00035","article-title":"Increase of ATP levels by glutamate antagonists is unrelated to neuroprotection.","volume":"5","author":"Riepe","year":"1994","journal-title":"Neuroreport"},{"key":"B86","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/s0168-9525(01)02625-7","article-title":"Lessons from animal models of Huntington\u2019s disease.","volume":"18","author":"Rubinsztein","year":"2002","journal-title":"Trends. Genet."},{"key":"B87","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.bbr.2006.10.004","article-title":"Adenosine A2A receptor blockade before striatal excitotoxic lesions prevents long term behavioral disturbances in the quinolinic rat model of Huntington\u2019s disease.","volume":"176","author":"Scattoni","year":"2007","journal-title":"Behav. Brain. Res."},{"key":"B88","doi-asserted-by":"publisher","first-page":"2871","DOI":"10.1093\/hmg\/ddi319","article-title":"HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism.","volume":"14","author":"Seong","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"B89","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.3390\/ijms15022024","article-title":"Adenosine receptors: expression, function and regulation.","volume":"15","author":"Sheth","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1002\/mds.23685","article-title":"Milestones in huntington disease.","volume":"26","author":"Shoulson","year":"2011","journal-title":"Mov. Disord."},{"key":"B91","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.nbd.2013.05.013","article-title":"Association between caffeine intake and age at onset in Huntington\u2019s disease.","volume":"58","author":"Simonin","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"B92","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1111\/jnc.14723","article-title":"Alterations in synaptic functions and plasticity in Huntington disease.","volume":"150","author":"Smith-Dijak","year":"2019","journal-title":"J. Neurochem."},{"key":"B93","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1093\/brain\/103.1.179","article-title":"Neurochemical alterations in Huntington\u2019s chorea: a study of post-mortem brain tissue.","volume":"103","author":"Spokes","year":"1980","journal-title":"Brain"},{"key":"B94","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.ncl.2020.01.010","article-title":"Medical, surgical, and genetic treatment of Huntington disease.","volume":"38","author":"Stahl","year":"2020","journal-title":"Neurol. Clin."},{"key":"B95","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/molecules22040676","article-title":"Adenosine A1 and A2A receptors in the brain: current research and their role in neurodegeneration.","volume":"22","author":"Stockwell","year":"2017","journal-title":"Molecules"},{"key":"B96","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/s10048-010-0248-3","article-title":"Age at onset in Huntington\u2019s disease: replication study on the associations of ADORA2A, HAP1 and OGG1.","volume":"11","author":"Taherzadeh-Fard","year":"2010","journal-title":"Neurogenetics"},{"key":"B97","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.nbd.2006.01.014","article-title":"Early and transient alteration of adenosine A2A receptor signaling in a mouse model of Huntington disease.","volume":"23","author":"Tarditi","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"B98","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-e","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes.","volume":"72","year":"1993","journal-title":"Cell"},{"key":"B99","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1080\/1527770.2016.1154969","article-title":"Changes in cardiac nucleotide metabolism in Huntington\u2019s disease.","volume":"35","author":"Toczek","year":"","journal-title":"Nucleosides. Nucleotides. Nucleic. Acids."},{"key":"B100","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1080\/15257770.2018.1481508","article-title":"Characterization of adenine nucleotide metabolism in the cellular model of Huntington\u2019s disease.","volume":"37","author":"Toczek","year":"2018","journal-title":"Nucleosides. Nucleotides. Nucleic. Acids."},{"key":"B101","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1016\/j.bbadis.2016.08.019","article-title":"An impaired metabolism of nucleotides underpins a novel mechanism of cardiac remodeling leading to Huntington\u2019s disease related cardiomyopathy.","volume":"1862","author":"Toczek","year":"","journal-title":"Biochim. Biophys. Acta"},{"key":"B102","doi-asserted-by":"publisher","first-page":"2148","DOI":"10.1002\/ajmg.b.30223","article-title":"Aberrant A2A receptor function in peripheral blood cells in Huntington\u2019s disease.","volume":"17","author":"Varani","year":"2003","journal-title":"FASEB. J."},{"key":"B103","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s12017-013-8219-0","article-title":"Increased 5-methylcytosine and decreased 5-hydroxymethylcytosine levels are associated with reduced striatal A2AR levels in Huntington\u2019s disease.","volume":"15","author":"Villar-Men\u00e9ndez","year":"2013","journal-title":"NeuroMolecular. Med."},{"key":"B104","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/0014-2999(94)90762-5","article-title":"Chronic adenosine A1 receptor agonist and antagonist: effect on receptor density and N-methyl-D-aspartate induced seizures in mice.","volume":"253","author":"Von Lubitz","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1002\/ana.410180207","article-title":"Neurotransmitter receptor alterations in Huntington\u2019s disease: Autoradiographic and homogenate studies with special reference to benzodiazepine receptor complexes.","volume":"18","author":"Whitehouse","year":"1985","journal-title":"Ann. Neurol."},{"key":"B106","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.bbamcr.2008.01.024","article-title":"Nucleotide- and nucleoside- converting ectoenzymes: Important modulators of purinergic signalling cascade.","volume":"1783","author":"Yegutkin","year":"2008","journal-title":"Biochem. Biophys. Acta."},{"key":"B107","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1523\/JNEUROSCI.11-05-01375-1991","article-title":"Adenosine inhibits excitatory but not inhibitory synaptic transmission in the hippocampus.","volume":"11","author":"Yoon","year":"1991","journal-title":"J. Neurosci."},{"key":"B108","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s11302-020-09755-6","article-title":"Ectonucleoside triphosphate diphosphohydrolases and ecto-5\u2032-nucleotidase in purinergic signaling: how the field developed and where we are now.","volume":"17","author":"Zimmermann","year":"2021","journal-title":"Purinergic Signal."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2021.657338\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T13:39:42Z","timestamp":1625146782000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2021.657338\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,1]]},"references-count":108,"alternative-id":["10.3389\/fnins.2021.657338"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2021.657338","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,1]]},"article-number":"657338"}}