{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:36:22Z","timestamp":1791689782180,"version":"4.3.4"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T00:00:00Z","timestamp":1520380800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"DOI":"10.3389\/fnins.2018.00137","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T04:42:50Z","timestamp":1520397770000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":53,"title":["Caffeine Protects Dopaminergic Neurons From Dopamine-Induced Neurodegeneration via Synergistic Adenosine-Dopamine D2-Like Receptor Interactions in Transgenic Caenorhabditis elegans"],"prefix":"10.3389","volume":"12","author":[{"given":"Rafael V. M.","family":"Manalo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M. B.","family":"Medina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,3,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.14348\/molcells.2016.2298","article-title":"Caffeine induces the stress response and up-regulates heat shock proteins in Caenorhabditis elegans","volume":"39","author":"Al-Amin","year":"2016","journal-title":"Mol. Cells"},{"key":"B2","doi-asserted-by":"publisher","first-page":"279","DOI":"10.3389\/fgene.2014.00279","article-title":"Use of Caenorhabditis elegans as a model to study Alzheimer's disease and other neurodegenerative diseases","volume":"5","author":"Alexander","year":"2014","journal-title":"Front. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.4103\/1673-5374.194716","article-title":"Pretreatment of caffeine leads to partial neuroprotection in MPTP model of Parkinson's disease","volume":"11","author":"Bagga","year":"2016","journal-title":"Neural Regen. Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/B978-0-12-394620-1.00013-8","article-title":"Analyses of C. elegans fat metabolic pathways","volume":"107","author":"Barros","year":"2012","journal-title":"Methods Cell Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/S0014-4886(03)00402-3","article-title":"Adenosine receptors and L-DOPA-induced dyskinesia in Parkinson's disease: potential targets for a new therapeutic approach","volume":"184","author":"Blandini","year":"2003","journal-title":"Exp. Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.neurobiolaging.2007.05.011","article-title":"A Caenorhabditis elegans model of tau hyperphosphorylation: induction of developmental defects by transgenic overexpression of Alzheimer's disease-like modified tau","volume":"30","author":"Brandt","year":"2009","journal-title":"Neurobiol. Aging"},{"key":"B7","doi-asserted-by":"publisher","first-page":"220","DOI":"10.3389\/fnagi.2015.00220","article-title":"Lifespan extension induced by caffeine in Caenorhabditis elegans is partially dependent on adenosine signaling","volume":"7","author":"Bridi","year":"2015","journal-title":"Front. Aging Neurosci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"71","DOI":"10.2174\/1570159X13666141210215655","article-title":"Caffeine: cognitive and physical performance enhancer or psychoactive drug?","volume":"13","author":"Cappelletti","year":"2015","journal-title":"Curr. Neuropharmacol."},{"key":"B9","doi-asserted-by":"crossref","first-page":"RC143","DOI":"10.1523\/JNEUROSCI.21-10-j0001.2001","article-title":"Neuroprotection by Caffeine and A2A adenosine receptor inactivation in a model of parkinson's disease","volume":"21","author":"Chen","year":"2001","journal-title":"J. Neurosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"216","DOI":"10.2460\/ajvr.2003.64.216","article-title":"Antagonism of adenosine receptors by caffeine and caffeine metabolites in equine forebrain tissues","volume":"64","author":"Chou","year":"2003","journal-title":"Am. J. Vet. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S1043-2760(01)00475-1","article-title":"Ion-channel regulation by G proteins","volume":"12","author":"Dascal","year":"2001","journal-title":"Trends Endocrinol. Metab."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3587","DOI":"10.1093\/hmg\/dds190","article-title":"Inhibition of tau aggregation in a novel Caenorhabditis elegans model of tauopathy mitigates proteotoxicity","volume":"21","author":"Fatouros","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"B13","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1523\/JNEUROSCI.22-03-01054.2002","article-title":"Persistent behavioral sensitization to chronic L-DOPA requires A2A adenosine receptors","volume":"22","author":"Freduzzi","year":"2002","journal-title":"J. Neurosci"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1111\/j.1471-4159.2007.05196.x","article-title":"An update on the mechanisms of the psychostimulant effects of caffeine","volume":"105","author":"Ferr\u00e9","year":"","journal-title":"J. Neurochem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.2174\/138161208784480108","article-title":"An update on adenosine A2A-dopamine D2 receptor interactions: implications for the function of G protein-coupled receptors","volume":"14","author":"Ferr\u00e9","year":"","journal-title":"Curr. Pharm. Des."},{"key":"B16","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0022-3565(24)34969-9","article-title":"Amplification of the Cyclic AMP Response to Forskolin in Pheochromocytoma PC12 Cells through Adenosine A2A Purinoceptors","volume":"290","author":"Florio","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.neuroscience.2014.01.025","article-title":"The role of D2-autoreceptors in regulating dopamine neuron activity and transmission","volume":"282","author":"Ford","year":"2014","journal-title":"Neuroscience"},{"key":"B18","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0031-6997(25)06782-1","article-title":"Nomenclature and classification of purinoceptors","volume":"46","author":"Fredholm","year":"1994","journal-title":"Pharmacol. Rev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1385\/JMN:26:2-3:209","article-title":"Adenosine A2A and dopamine D2 heteromeric receptor complexes and their function","volume":"26","author":"Fuxe","year":"2005","journal-title":"J. Mol. Neurosci."},{"key":"B20","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0022-3565(25)10554-5","article-title":"Does adenosine receptor blockade mediate caffeine-induced rotational behavior?","volume":"274","author":"Garrett","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s12640-014-9501-0","article-title":"The Role of Adenosine A1 and A2A receptors in the caffeine effect on MDMA-induced, D. A., and 5-HT Release in the Mouse Striatum","volume":"27","author":"G\u00f3rska","year":"2015","journal-title":"Neurotox. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2637","DOI":"10.1016\/0024-3205(89)90249-X","article-title":"Caffeine and regional brain monoamine utilization in mice","volume":"45","author":"Hadfield","year":"1989","journal-title":"Life Sci."},{"key":"B23","article-title":"The neuronal genome of Caenorhabditis elegans,","author":"Hobert","year":"2005","journal-title":"Wormbook: The Online Review of C. elegans Biology"},{"key":"B24","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1212\/WNL.84.14_supplement.S16.006","article-title":"EHTTM coffee extract: A neuroprotective agent and modulator of PP2A methylation with anti-inflammatory and antioxidant properties","volume":"84","author":"Huber","year":"2015","journal-title":"Neurology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1111\/cns.12684","article-title":"The neuroprotective effects of caffeine in neurodegenerative diseases","volume":"23","author":"Kolahdouzan","year":"2017","journal-title":"CNS Neurosci. Ther."},{"key":"B26","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s13311-012-0165-2","article-title":"Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson's disease","volume":"10","author":"Lee","year":"2013","journal-title":"Neurotherapeutics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1016\/j.exger.2006.06.059","article-title":"C. elegans models of age-associated neurodegenerative diseases: lessons from transgenic worm models of Alzheimer's disease","volume":"41","author":"Link","year":"2006","journal-title":"Exp. Gerontol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3390\/biomedicines5020017","article-title":"Coconut (Cocos nucifera) ethanolic leaf extract reduces Amyloid-\u03b2 (1-42) aggregation and paralysis prevalence in transgenic Caenorhabditis elegans independently of free radical scavenging and acetylcholinesterase inhibition","volume":"5","author":"Manalo","year":"2017","journal-title":"Biomedicines"},{"key":"B29","doi-asserted-by":"publisher","first-page":"20938","DOI":"10.1038\/srep20938","article-title":"Caffeine promotes wakefulness via dopamine signaling in Drosophila","volume":"6","author":"Nall","year":"2016","journal-title":"Sci. Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1159\/000315496","article-title":"Prior treatment (priming) with caffeine sensitizes D2-dopamine-mediated contralateral rotational behavior in 6-hydroxydopamine-lesioned rats","volume":"86","author":"Pollack","year":"2010","journal-title":"Pharmacology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/S0304-3940(96)13143-8","article-title":"Adenosine A1 receptor blockade selectively potentiates the motor effects induced by dopamine D1 receptor stimulation in rodents","volume":"218","author":"Popoli","year":"1996","journal-title":"Neurosci. Lett."},{"key":"B32","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1212\/WNL.0b013e318263570d","article-title":"Caffeine for treatment of Parkinson's disease: a randomized controlled trial","volume":"79","author":"Postuma","year":"2012","journal-title":"Neurology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.3233\/JAD-2010-1379","article-title":"Caffeine and adenosine","volume":"20","author":"Ribeiro","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1212\/01.wnl.0000266670.35219.0c","article-title":"The neuroprotective effects of caffeine: a prospective population study (the Three City Study)","volume":"69","author":"Ritchie","year":"2007","journal-title":"Neurology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"42","DOI":"10.2174\/1874205X01610010042","article-title":"Potential role of caffeine in the treatment of Parkinson's disease","volume":"10","author":"Roshan","year":"2016","journal-title":"Open Neurol. J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2674","DOI":"10.1001\/jama.283.20.2674","article-title":"Association of coffee and caffeine intake with the risk of parkinson disease","volume":"283","author":"Ross","year":"2000","journal-title":"JAMA"},{"key":"B37","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/S0014-2999(98)00302-1","article-title":"Involvement of adenosine A2A receptor in sleep promotion","volume":"351","author":"Satoh","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1212\/WNL.0b013e318263580e","article-title":"Caffeine in Parkinson disease: better for cruise control than snooze patrol?","volume":"79","author":"Schwarzchild","year":"2012","journal-title":"Neurology"},{"key":"B39","unstructured":"SteirnagleT. Maintenance of C. elegans1999"},{"key":"B40","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1111\/j.2042-7158.1973.tb10012.x","article-title":"Behavioural and biochemical interaction between caffeine and L-dopa","volume":"25","author":"Str\u00f6mberg","year":"1973","journal-title":"J. Pharm. Pharmacol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/2046-2395-1-9","article-title":"Caffeine extends life span, improves healthspan, and delays age-associated pathology in Caenorhabditis elegans","volume":"1","author":"Sutphin","year":"2012","journal-title":"Longev. Healthspan"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1091\/mbc.E11-11-0926","article-title":"Cell survival, DNA damage and oncogenic transformation after a transient and reversible apoptotic response","volume":"23","author":"Tang","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"B43","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1523\/JNEUROSCI.17-07-02519.1997","article-title":"Functional Roles of Dopamine D2 and D3 autoreceptors on nigostriatal neurons analyzed by antisense knockdown in vivo.","volume":"17","author":"Tepper","year":"1997","journal-title":"J. Neurosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"5525","DOI":"10.1523\/JNEUROSCI.4777-09.2010","article-title":"Decaffeinated coffee and nicotine-free tobacco provide neuroprotection in Drosophila Models of Parkinson's Disease through an NRF2-dependent mechanism","volume":"30","author":"Trinh","year":"2010","journal-title":"J. Neurosci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"942","DOI":"10.4161\/psb.4.10.9530","article-title":"Signaling through G protein coupled receptors","volume":"4","author":"Tuteja","year":"2009","journal-title":"Plant Signal. Behav."},{"key":"B46","doi-asserted-by":"publisher","first-page":"7319","DOI":"10.1038\/ncomms8319","article-title":"Neurodegeneration in C. elegans models of ALS requires TIR-1\/Sarm1 immune pathway activation in neurons","volume":"6","author":"V\u00e9ri\u00e8pe","year":"2015","journal-title":"Nat. Commun."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e549","DOI":"10.1038\/tp.2015.46","article-title":"Caffeine increases striatal dopamine D2\/D3 receptor availability in the human brain","volume":"5","author":"Volkow","year":"2015","journal-title":"Transl. Psychiatr."},{"key":"B48","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1021\/cn100010p","article-title":"Antipsychotic drugs activate the C. elegans Akt pathway via the DAF-2 insulin\/IGF-1 receptor","volume":"1","author":"Weeks","year":"2010","journal-title":"ACS Chem. Neurosci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3109\/00207459309000599","article-title":"Amphetamine-induced rotational behavior in rats: relationship to hypothalamic and striatal degeneration","volume":"71","author":"Willis","year":"1993","journal-title":"Int. J. Neurosci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1002\/mds.25319","article-title":"Caffeine consumption and risk of dyskinesia in CALM-PD","volume":"28","author":"Wills","year":"2013","journal-title":"Mov. Disord."},{"key":"B51","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/B978-0-12-384878-9.00015-7","article-title":"Watching worms wither: modeling neurodegeneration in C. elegans.","volume":"100","author":"Wolozin","year":"2011","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.brainres.2010.08.099","article-title":"Deletion of adenosine A1 or A(2A) receptors reduces L-3,4-dihydroxyphenylalanine-induced dyskinesia in a model of Parkinson's disease","volume":"1367","author":"Xiao","year":"2011","journal-title":"Brain Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.neuroscience.2016.02.035","article-title":"Neuroprotection by caffeine in the MPTP model of parkinson's disease and its dependence on adenosine A2A receptors","volume":"322","author":"Xu","year":"2016","journal-title":"Neuroscience"},{"key":"B54","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.neuroscience.2010.02.020","article-title":"Neuroprotection by caffeine: time course and role of its metabolites in the MPTP model of Parkinson Disease","volume":"167","author":"Xu","year":"2010","journal-title":"Neuroscience"},{"key":"B55","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.neulet.2005.09.036","article-title":"Cross-sensitization between caffeine- and L-dopa-induced behaviors in hemiparkinsonian mice","volume":"393","author":"Yu","year":"2006","journal-title":"Neurosci. Lett."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fnins.2018.00137\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T12:44:36Z","timestamp":1751460276000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fnins.2018.00137\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,7]]},"references-count":55,"alternative-id":["10.3389\/fnins.2018.00137"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2018.00137","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,7]]},"article-number":"137"}}