{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:37:39Z","timestamp":1792607859250,"version":"4.5.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Purinergic Signalling"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1007\/s11302-026-10160-8","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T12:00:51Z","timestamp":1778760051000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Purinergic modulation in Parkinson\u2019s disease: the dual role of istradefylline in motor and cognitive outcomes"],"prefix":"10.1007","volume":"22","author":[{"given":"Mokhtar","family":"Rejili","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayder M.","family":"Al-kuraishy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali I.","family":"Al-Gareeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali K.","family":"Albuhadily","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid S.","family":"Jabir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa M.","family":"Shokr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaber El-Saber","family":"Batiha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"10160_CR1","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.neuropharm.2018.09.036","volume":"143","author":"K Ishibashi","year":"2018","unstructured":"Ishibashi K, Miura Y, Wagatsuma K, Toyohara J, Ishiwata K, Ishii K (2018) Occupancy of adenosine A2A receptors by istradefylline in patients with Parkinson\u2019s disease using 11C-preladenant PET. Neuropharmacology 143:106\u2013112. https:\/\/doi.org\/10.1016\/j.neuropharm.2018.09.036","journal-title":"Neuropharmacology"},{"key":"10160_CR2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.2147\/dnnd.s245197","volume":"12","author":"SH Isaacson","year":"2022","unstructured":"Isaacson SH, Bett\u00e9 S, Pahwa R (2022) Istradefylline for OFF episodes in Parkinson\u2019s disease: a US perspective of common clinical scenarios. Degener Neurol Neuromuscul Dis 12:97. https:\/\/doi.org\/10.2147\/dnnd.s245197","journal-title":"Degener Neurol Neuromuscul Dis"},{"key":"10160_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2022.136515","volume":"774","author":"XL Wang","year":"2022","unstructured":"Wang XL, Feng ST, Chen B, Hu D, Wang ZZ, Zhang Y (2022) Efficacy and safety of istradefylline for Parkinson\u2019s disease: a systematic review and meta-analysis. Neurosci Lett 774:136515. https:\/\/doi.org\/10.1016\/j.neulet.2022.136515","journal-title":"Neurosci Lett"},{"key":"10160_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2021.120078","volume":"432","author":"M Takahashi","year":"2022","unstructured":"Takahashi M, Shimokawa T, Koh J, Takeshima T, Yamashita H, Kajimoto Y, Mori A, Ito H (2022) Efficacy and safety of istradefylline in patients with Parkinson\u2019s disease presenting with postural abnormalities: results from a multicenter, prospective, and open-label exploratory study in Japan. J Neurol Sci 432:120078. https:\/\/doi.org\/10.1016\/j.jns.2021.120078","journal-title":"J Neurol Sci"},{"key":"10160_CR5","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.nbd.2017.10.014","volume":"110","author":"AG Orr","year":"2018","unstructured":"Orr AG, Lo I, Schumacher H, Ho K, Gill M, Guo W, Kim DH, Knox A, Saito T, Saido TC, Simms J, Toddes C, Wang X, Yu GQ, Mucke L (2018) Istradefylline reduces memory deficits in aging mice with amyloid pathology. Neurobiol Dis 110:29\u201336. https:\/\/doi.org\/10.1016\/j.nbd.2017.10.014","journal-title":"Neurobiol Dis"},{"issue":"11","key":"10160_CR6","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/s41531-025-01004-0","volume":"111","author":"M Palanivel","year":"2025","unstructured":"Palanivel M, Ghosh KK, Mallam M, Bhuvanakantham R, Padmanabhan P, Lim KL, Guly\u00e1s B (2025) Imaging advances to detect non-motor prodromal markers of Parkinson\u2019s disease and explore therapeutic translation opportunities. Npj Park Dis 111(11):174. https:\/\/doi.org\/10.1038\/s41531-025-01004-0","journal-title":"Npj Park Dis"},{"key":"10160_CR7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23094508","volume":"23","author":"E Guatteo","year":"2022","unstructured":"Guatteo E, Berretta N, Monda V, Ledonne A, Mercuri NB (2022) Pathophysiological features of nigral dopaminergic neurons in animal models of Parkinson\u2019s disease. Int J Mol Sci 23:4508. https:\/\/doi.org\/10.3390\/ijms23094508","journal-title":"Int J Mol Sci"},{"key":"10160_CR8","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1021\/acsptsci.4c00564","volume":"8","author":"MM Shokr","year":"2025","unstructured":"Shokr MM, Badawi GA, Elshazly SM, Zaki HF, Mohamed AF (2025) Sigma 1 receptor and its pivotal role in neurological disorders. ACS Pharmacol Transl Sci 8:47\u201365. https:\/\/doi.org\/10.1021\/acsptsci.4c00564","journal-title":"ACS Pharmacol Transl Sci"},{"key":"10160_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2025.157010","volume":"194","author":"SM Alshahrani","year":"2025","unstructured":"Alshahrani SM, Al-kuraishy HM, Al-Gareeb AI, Shokr MM, Alexiou A, Papadakis M, Batiha GES (2025) Dysregulation of the leukotriene pathway in Parkinson\u2019s disease: the potential role of montelukast. Cytokine 194:157010. https:\/\/doi.org\/10.1016\/j.cyto.2025.157010","journal-title":"Cytokine"},{"key":"10160_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177830","author":"SM Alshahrani","year":"2025","unstructured":"Alshahrani SM, Al-kuraishy HM, Al-Gareeb AI, Albuhadily AK, Shokr MM, Kadasah SF, Alexiou A, Papadakis M, El-Saber Batiha G (2025) LRP1 at the crossroads of Parkinson\u2019s and Alzheimer\u2019s: divergent roles in \u03b1-synuclein and amyloid pathology. Eur J Pharmacol. https:\/\/doi.org\/10.1016\/j.ejphar.2025.177830","journal-title":"Eur J Pharmacol"},{"key":"10160_CR11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25073995","author":"PM Giri","year":"2024","unstructured":"Giri PM, Banerjee A, Ghosal A, Layek B (2024) Neuroinflammation in neurodegenerative disorders: current knowledge and therapeutic implications. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms25073995","journal-title":"Int J Mol Sci"},{"key":"10160_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177419","volume":"995","author":"MM Khowdiary","year":"2025","unstructured":"Khowdiary MM, Al-kuraishy HM, Al-Gareeb AI, Albuhadily AK, Elhenawy AA, Babalghith AO, Shokr MM, Alexiou A, Papadakis M, El-Saber Batiha G (2025) Dysregulation of serotonergic neurotransmission in Parkinson disease: a key duet. Eur J Pharmacol 995:177419. https:\/\/doi.org\/10.1016\/j.ejphar.2025.177419","journal-title":"Eur J Pharmacol"},{"key":"10160_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102481","volume":"101","author":"PT Kamatham","year":"2024","unstructured":"Kamatham PT, Shukla R, Khatri DK, Vora LK (2024) Pathogenesis, diagnostics, and therapeutics for Alzheimer\u2019s disease: breaking the memory barrier. Ageing Res Rev 101:102481. https:\/\/doi.org\/10.1016\/j.arr.2024.102481","journal-title":"Ageing Res Rev"},{"key":"10160_CR14","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-025-02000-9","author":"SM Alqahtani","year":"2025","unstructured":"Alqahtani SM, Al-kuraishy HM, Al-Gareeb AI, Albuhadily AK, Shokr MM, Alexiou A, Papadakis M, Batiha GES (2025) Pharmacological modulation of the PI3K\/AKT\/GSK3\u03b2 axis: a new frontier in Alzheimer\u2019s disease treatment. Inflammopharmacology. https:\/\/doi.org\/10.1007\/s10787-025-02000-9","journal-title":"Inflammopharmacology"},{"issue":"8","key":"10160_CR15","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1007\/s11011-025-01739-y","volume":"40","author":"MM Shokr","year":"2025","unstructured":"Shokr MM (2025) Rewiring brain immunity: targeting microglial metabolism for neuroprotection in neurodegenerative disorders. Metab Brain Dis 40:326. https:\/\/doi.org\/10.1007\/s11011-025-01739-y","journal-title":"Metab Brain Dis"},{"key":"10160_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002270","volume":"14","author":"HM Lanoisel\u00e9e","year":"2017","unstructured":"Lanoisel\u00e9e HM, Nicolas G, Wallon D, Rovelet-Lecrux A, Lacour M, Rousseau S, Richard AC, Pasquier F, Rollin-Sillaire A, Martinaud O, Quillard-Muraine M, de la Sayette V, Boutoleau-Bretonniere C, Etcharry-Bouyx F, Chauvir\u00e9 V, Sarazin M, le Ber I, Epelbaum S, Jonveaux T, Rouaud O, Ceccaldi M, F\u00e9lician O, Godefroy O, Formaglio M, Croisile B, Auriacombe S, Chamard L, Vincent JL, Sauv\u00e9e M, Marelli-Tosi C, Gabelle A, Ozsancak C, Pariente J, Paquet C, Hannequin D, Campion D (2017) APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: a genetic screening study of familial and sporadic cases. PLoS Med 14:e1002270. https:\/\/doi.org\/10.1371\/journal.pmed.1002270","journal-title":"PLoS Med"},{"key":"10160_CR17","doi-asserted-by":"publisher","first-page":"6635","DOI":"10.1007\/s10787-025-01940-6","volume":"33","author":"F Alshammari","year":"2025","unstructured":"Alshammari F, Al-Kuraishy HM, Shokr MM, Papadakis M, Alexiou A, Batiha GES (2025) Enterogenic dementia: defining the gut\u2013brain axis and the role of inflammatory bowel disease in cognitive impairment. Inflammopharmacology 33:6635\u20136655. https:\/\/doi.org\/10.1007\/s10787-025-01940-6","journal-title":"Inflammopharmacology"},{"key":"10160_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101503","volume":"72","author":"T Song","year":"2021","unstructured":"Song T, Song X, Zhu C, Patrick R, Skurla M, Santangelo I, Green M, Harper D, Ren B, Forester BP, \u00d6ng\u00fcr D, Du F (2021) Mitochondrial dysfunction, oxidative stress, neuroinflammation, and metabolic alterations in the progression of Alzheimer\u2019s disease: a meta-analysis of in vivo magnetic resonance spectroscopy studies. Ageing Res Rev 72:101503. https:\/\/doi.org\/10.1016\/j.arr.2021.101503","journal-title":"Ageing Res Rev"},{"key":"10160_CR19","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213954","volume":"23","author":"E Passeri","year":"2022","unstructured":"Passeri E, Elkhoury K, Morsink M, Broersen K, Linder M, Tamayol A, Malaplate C, Yen FT, Arab-Tehrany E (2022) Alzheimer\u2019s disease: treatment strategies and their limitations. Int J Mol Sci 23:13954. https:\/\/doi.org\/10.3390\/ijms232213954","journal-title":"Int J Mol Sci"},{"key":"10160_CR20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15022024","volume":"15","author":"S Sheth","year":"2014","unstructured":"Sheth S, Brito R, Mukherjea D, Rybak LP, Ramkumar V (2014) Adenosine receptors: expression, function and regulation. Int J Mol Sci 15:2024. https:\/\/doi.org\/10.3390\/ijms15022024","journal-title":"Int J Mol Sci"},{"issue":"22","key":"10160_CR21","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1007\/s11302-025-10114-6","volume":"222","author":"A Ismail","year":"2026","unstructured":"Ismail A, Al-kuraishy HM, Al-Gareeb AI, Albuhadily AK, Alkazmi LM, Albukhari AF, Shokr MM, Alexiou A, Papadakis M, Batiha GE-S (2026) The potential role of adenosinergic pathway and methylxanthines in Parkinson\u2019s disease: blowing in the wind or not. Purinergic Signal 222(22):24. https:\/\/doi.org\/10.1007\/s11302-025-10114-6","journal-title":"Purinergic Signal"},{"key":"10160_CR22","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1007\/s00415-022-11342-1","volume":"270","author":"I Waggan","year":"2023","unstructured":"Waggan I, Rissanen E, Tuisku J, Joutsa J, Helin S, Parkkola R, Rinne JO, Airas L (2023) Adenosine A2A receptor availability in patients with early- and moderate-stage Parkinson\u2019s disease. J Neurol 270:300\u2013310. https:\/\/doi.org\/10.1007\/s00415-022-11342-1","journal-title":"J Neurol"},{"key":"10160_CR23","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1093\/brain\/awh128","volume":"127","author":"F Calon","year":"2004","unstructured":"Calon F, Dridi M, Hornykiewicz O, B\u00e9dard PJ, Rajput AH, Di Paolo T (2004) Increased adenosine A2A receptors in the brain of Parkinson\u2019s disease patients with dyskinesias. Brain 127:1075\u20131084. https:\/\/doi.org\/10.1093\/brain\/awh128","journal-title":"Brain"},{"key":"10160_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041719","volume":"22","author":"K Prasad","year":"2021","unstructured":"Prasad K, de Vries EFJ, Elsinga PH, Dierckx RAJO, van Waarde A (2021) Allosteric interactions between adenosine A2A and dopamine D2 receptors in heteromeric complexes: biochemical and pharmacological characteristics, and opportunities for PET imaging. Int J Mol Sci 22:1719. https:\/\/doi.org\/10.3390\/ijms22041719","journal-title":"Int J Mol Sci"},{"key":"10160_CR25","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1093\/cercor\/bhv268","volume":"27","author":"DG Ferreira","year":"2017","unstructured":"Ferreira DG, Batalha VL, Miranda HV, Coelho JE, Gomes R, Gon\u00e7alves FQ, Real JI, Rino J, Albino-Teixeira A, Cunha RA, Outeiro TF, Lopes LV (2017) Adenosine A2A receptors modulate \u03b1-synuclein aggregation and toxicity. Cereb Cortex 27:718\u2013730. https:\/\/doi.org\/10.1093\/cercor\/bhv268","journal-title":"Cereb Cortex"},{"key":"10160_CR26","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.expneurol.2016.05.040","volume":"283","author":"Q Hu","year":"2016","unstructured":"Hu Q, Ren X, Liu Y, Li Z, Zhang L, Chen X, He C, Chen JF (2016) Aberrant adenosine A2A receptor signaling contributes to neurodegeneration and cognitive impairments in a mouse model of synucleinopathy. Exp Neurol 283:213\u2013223. https:\/\/doi.org\/10.1016\/j.expneurol.2016.05.040","journal-title":"Exp Neurol"},{"key":"10160_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2025.1695486","volume":"12","author":"G Kocak","year":"2025","unstructured":"Kocak G, Dimas MM, Silva LFSE, Silva-Amaral D, Sun C, Cruddas S, Barrett T, Martins-de-Souza D, Cunha-Neto E, Brocardo PS, Kataura T, Korolchuk VI, Sarkar S (2025) Autophagy\u2013NAD+ axis: emerging insights into neuronal homeostasis and neurodegenerative diseases. Front Mol Biosci 12:1695486. https:\/\/doi.org\/10.3389\/fmolb.2025.1695486","journal-title":"Front Mol Biosci"},{"key":"10160_CR28","doi-asserted-by":"publisher","first-page":"5799","DOI":"10.1007\/s10787-025-01955-z","volume":"33","author":"MM Shokr","year":"2025","unstructured":"Shokr MM (2025) Beyond the blood\u2013brain barrier: unraveling T cell subsets in CNS immunity and disease. Inflammopharmacology 33:5799\u20135818. https:\/\/doi.org\/10.1007\/s10787-025-01955-z","journal-title":"Inflammopharmacology"},{"key":"10160_CR29","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1347987","volume":"16","author":"A Adamu","year":"2024","unstructured":"Adamu A, Li S, Gao F, Xue G (2024) The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets. Front Aging Neurosci 16:1347987. https:\/\/doi.org\/10.3389\/fnagi.2024.1347987","journal-title":"Front Aging Neurosci"},{"key":"10160_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/cells14201585","volume":"14","author":"V Salmaso","year":"2025","unstructured":"Salmaso V, Menin S, Moro S, Spalluto G, Federico S (2025) Adenosine receptors in neuroinflammation and neurodegeneration. Cells 14:1585. https:\/\/doi.org\/10.3390\/cells14201585","journal-title":"Cells"},{"key":"10160_CR31","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1097\/01.jnen.0000235120.59935.f5","volume":"65","author":"A Rodr\u00edguez","year":"2006","unstructured":"Rodr\u00edguez A, Mart\u00edn M, Albasanz JL, Barrachina M, Espinosa JC, Torres JM, Ferrer I (2006) Adenosine A1 receptor protein levels and activity is increased in the cerebral cortex in Creutzfeldt-Jakob disease and in bovine spongiform encephalopathy-infected bovine-PrP mice. J Neuropathol Exp Neurol 65:964\u2013975. https:\/\/doi.org\/10.1097\/01.jnen.0000235120.59935.f5","journal-title":"J Neuropathol Exp Neurol"},{"key":"10160_CR32","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.3233\/jpd-212672","volume":"11","author":"RA Hauser","year":"2021","unstructured":"Hauser RA, Hattori N, Fernandez H, Isaacson SH, Mochizuki H, Rascol O, Stocchi F, Li J, Mori A, Nakajima Y, Ristuccia R, Lewitt P (2021) Efficacy of Istradefylline, an adenosine A2A receptor antagonist, as adjunctive therapy to levodopa in Parkinson\u2019s disease: a pooled analysis of 8 phase 2b\/3 trials. J Parkinsons Dis 11:1663\u20131675. https:\/\/doi.org\/10.3233\/jpd-212672","journal-title":"J Parkinsons Dis"},{"key":"10160_CR33","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23095056","volume":"23","author":"S Merighi","year":"2022","unstructured":"Merighi S, Nigro M, Travagli A, Pasquini S, Borea PA, Varani K, Vincenzi F, Gessi S (2022) A2A adenosine receptor: a possible therapeutic target for Alzheimer\u2019s disease by regulating NLRP3 inflammasome activity? Int J Mol Sci 23:5056. https:\/\/doi.org\/10.3390\/ijms23095056","journal-title":"Int J Mol Sci"},{"key":"10160_CR34","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27072366","volume":"27","author":"A Mori","year":"2022","unstructured":"Mori A, Chen JF, Uchida S, Durlach C, King SM, Jenner P (2022) The pharmacological potential of adenosine A2A receptor antagonists for treating Parkinson\u2019s disease. Molecules 27:2366. https:\/\/doi.org\/10.3390\/molecules27072366","journal-title":"Molecules"},{"key":"10160_CR35","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26125680","volume":"26","author":"MG Zaki","year":"2025","unstructured":"Zaki MG, Jakova E, Pordeli M, Setork E, Taghibiglou C, Cayabyab FS (2025) The anti-Parkinsonian A2A receptor antagonist istradefylline (KW-6002) attenuates behavioral abnormalities, neuroinflammation, and neurodegeneration in cerebral ischemia: an adenosinergic signaling link between stroke and Parkinson\u2019s disease. Int J Mol Sci 26:26. https:\/\/doi.org\/10.3390\/ijms26125680","journal-title":"Int J Mol Sci"},{"issue":"12","key":"10160_CR36","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3390\/neurolint12030017","volume":"12","author":"AA Berger","year":"2020","unstructured":"Berger AA, Winnick A, Welschmeyer A, Kaneb A, Berardino K, Cornett EM, Kaye AD, Viswanath O, Urits I (2020) Istradefylline to treat patients with Parkinson\u2019s disease experiencing \u201coff\u201d episodes: a comprehensive review. Neurol Int 12(12):109\u2013129. https:\/\/doi.org\/10.3390\/neurolint12030017","journal-title":"Neurol Int"},{"key":"10160_CR37","doi-asserted-by":"publisher","DOI":"10.1097\/WNF.0000000000000620","volume":"48","author":"Y Torres-Yaghi","year":"2025","unstructured":"Torres-Yaghi Y, Qian J, Cummings H, Shimoda H, Ito S, Batson S, Mitchell S, Pagan F (2025) Comparative safety of istradefylline among Parkinson disease adjunctive therapies: a systematic review and meta-analysis of randomized controlled studies. Clin Neuropharmacol 48:7. https:\/\/doi.org\/10.1097\/WNF.0000000000000620","journal-title":"Clin Neuropharmacol"},{"key":"10160_CR38","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4892473","volume":"2018","author":"MD Bagatini","year":"2018","unstructured":"Bagatini MD, Dos Santos AA, Cardoso AM, M\u00e2nica A, Reschke CR, Carvalho FB (2018) The impact of purinergic system enzymes on noncommunicable, neurological, and degenerative diseases. J Immunol Res 2018:4892473. https:\/\/doi.org\/10.1155\/2018\/4892473","journal-title":"J Immunol Res"},{"key":"10160_CR39","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1080\/25785826.2022.2094593","volume":"45","author":"M Tokano","year":"2022","unstructured":"Tokano M, Kawano M, Takagi R, Matsushita S (2022) Istradefylline, an adenosine A2a receptor antagonist, inhibits the CD4+ T-cell hypersecretion of IL-17A and IL-8 in humans. Immunol Med 45:244\u2013250. https:\/\/doi.org\/10.1080\/25785826.2022.2094593","journal-title":"Immunol Med"},{"key":"10160_CR40","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.nbd.2018.07.014","volume":"118","author":"Y Ogawa","year":"2018","unstructured":"Ogawa Y, Furusawa E, Saitoh T, Sugimoto H, Omori T, Shimizu S, Kondo H, Yamazaki M, Sakuraba H, Oishi K (2018) Inhibition of astrocytic adenosine receptor A2A attenuates microglial activation in a mouse model of Sandhoff disease. Neurobiol Dis 118:142\u2013154. https:\/\/doi.org\/10.1016\/j.nbd.2018.07.014","journal-title":"Neurobiol Dis"},{"key":"10160_CR41","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jns.2018.11.005","volume":"396","author":"H Nagayama","year":"2019","unstructured":"Nagayama H, Kano O, Murakami H, Ono K, Hamada M, Toda T, Sengoku R, Shimo Y, Hattori N (2019) Effect of istradefylline on mood disorders in Parkinson\u2019s disease. J Neurol Sci 396:78\u201383. https:\/\/doi.org\/10.1016\/j.jns.2018.11.005","journal-title":"J Neurol Sci"},{"key":"10160_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-025-03115-9","volume":"30","author":"A Launay","year":"2025","unstructured":"Launay A, Carvalho K, Genin A, Gauvrit T, Nobili P, Gomez-Murcia V, Augustin E, Burgard A, Gambi J, Fourmy D, Thiroux B, Vieau D, Bemelmans AP, Le Gras S, Bu\u00e9e L, Orr ME, Audinat E, Boutillier AL, Bonvento G, Cambon K, Faivre E, Blum D (2025) Upregulation of adenosine A2A receptor in astrocytes is sufficient to trigger hippocampal multicellular dysfunctions and memory deficits. Mol Psychiatry 30:5300. https:\/\/doi.org\/10.1038\/s41380-025-03115-9","journal-title":"Mol Psychiatry"},{"key":"10160_CR43","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13111551","volume":"13","author":"A Anirudhan","year":"2023","unstructured":"Anirudhan A, Mahema S, Ahmad SF, Bin Emran T, Ahmed SSSJ, Paramasivam P (2023) Screening of crucial cytosolicproteins interconnecting the endoplasmic reticulum and mitochondria in Parkinson\u2019s disease and the impact of anti-Parkinson drugs in the preservation of organelle connectivity. Brain Sci 13:1551. https:\/\/doi.org\/10.3390\/brainsci13111551","journal-title":"Brain Sci"},{"key":"10160_CR44","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.neuropharm.2014.04.006","volume":"83","author":"A Jer\u00f3nimo-Santos","year":"2014","unstructured":"Jer\u00f3nimo-Santos A, Batalha VL, M\u00fcller CE, Baqi Y, Sebasti\u00e3o AM, Lopes LV, Di\u00f3genes MJ (2014) Impact of in vivo chronic blockade of adenosine A2A receptors on the BDNF-mediated facilitation of LTP. Neuropharmacology 83:99\u2013106. https:\/\/doi.org\/10.1016\/j.neuropharm.2014.04.006","journal-title":"Neuropharmacology"},{"key":"10160_CR45","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21031170","volume":"21","author":"E Palasz","year":"2020","unstructured":"Palasz E, Wysocka A, Gasiorowska A, Chalimoniuk M, Niewiadomski W, Niewiadomska G (2020) BDNF as a promising therapeutic agent in Parkinson\u2019s disease. Int J Mol Sci 21:1170. https:\/\/doi.org\/10.3390\/ijms21031170","journal-title":"Int J Mol Sci"},{"key":"10160_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.ensci.2020.100257","volume":"20","author":"M Suzuki","year":"2020","unstructured":"Suzuki M, Arai M, Hayashi A, Ogino M (2020) Prescription pattern of anti-Parkinson\u2019s disease drugs in Japan based on a nationwide medical claims database. eNeurolSci 20:100257. https:\/\/doi.org\/10.1016\/j.ensci.2020.100257","journal-title":"eNeurolSci"},{"key":"10160_CR47","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s11302-020-09694-2","volume":"16","author":"JF Chen","year":"2020","unstructured":"Chen JF, Cunha RA (2020) The belated US FDA approval of the adenosine A2A receptor antagonist istradefylline for treatment of Parkinson\u2019s disease. Purinergic Signal 16:167. https:\/\/doi.org\/10.1007\/s11302-020-09694-2","journal-title":"Purinergic Signal"},{"key":"10160_CR48","doi-asserted-by":"publisher","first-page":"32","DOI":"10.9740\/MHC.2022.01.032","volume":"12","author":"L Cummins","year":"2022","unstructured":"Cummins L, Cates ME (2022) Istradefylline: a novel agent in the treatment of \u201coff\u201d episodes associated with levodopa\/carbidopa use in Parkinson disease. Ment Health Clin 12:32. https:\/\/doi.org\/10.9740\/MHC.2022.01.032","journal-title":"Ment Health Clin"},{"key":"10160_CR49","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1080\/14656566.2019.1614167","volume":"20","author":"M Iijima","year":"2019","unstructured":"Iijima M, Orimo S, Terashi H, Suzuki M, Hayashi A, Shimura H, Mitoma H, Kitagawa K, Okuma Y (2019) Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson\u2019s disease: a single-arm, open-label, prospective, multicenter study. Expert Opin Pharmacother 20:1405\u20131411. https:\/\/doi.org\/10.1080\/14656566.2019.1614167","journal-title":"Expert Opin Pharmacother"},{"key":"10160_CR50","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1097\/00002826-200201000-00005","volume":"25","author":"J Kulisevsky","year":"2002","unstructured":"Kulisevsky J, Barbanoj M, Gironell A, Antonijoan R, Casas M, Pascual-Sedano B (2002) A double-blind crossover, placebo-controlled study of the adenosine A2A antagonist theophylline in Parkinson\u2019s disease. Clin Neuropharmacol 25:25\u201331. https:\/\/doi.org\/10.1097\/00002826-200201000-00005","journal-title":"Clin Neuropharmacol"},{"key":"10160_CR51","doi-asserted-by":"publisher","first-page":"S45","DOI":"10.1016\/j.parkreldis.2020.10.024","volume":"80","author":"JF Chen","year":"2020","unstructured":"Chen JF, Schwarzschild MA (2020) Do caffeine and more selective adenosine A2A receptor antagonists protect against dopaminergic neurodegeneration in Parkinson\u2019s disease? Parkinsonism Relat Disord 80:S45. https:\/\/doi.org\/10.1016\/j.parkreldis.2020.10.024","journal-title":"Parkinsonism Relat Disord"},{"key":"10160_CR52","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.1212\/WNL.52.9.1916","volume":"52","author":"VS Kostic","year":"1999","unstructured":"Kostic VS, Suetel M, Sternic N, Dragaseuic N, Przedborski S (1999) Theophylline increases \u201con\u201d time in advanced parkinsonian patients. Neurology 52:1916\u20131916. https:\/\/doi.org\/10.1212\/WNL.52.9.1916","journal-title":"Neurology"},{"key":"10160_CR53","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1111\/j.2042-7158.1994.tb03840.x","volume":"46","author":"J Mally","year":"1994","unstructured":"Mally J, Stone TW (1994) The effect of theophylline on parkinsonian symptoms. J Pharm Pharmacol 46:515\u2013517. https:\/\/doi.org\/10.1111\/j.2042-7158.1994.tb03840.x","journal-title":"J Pharm Pharmacol"},{"key":"10160_CR54","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.602697","volume":"14","author":"X Ren","year":"2020","unstructured":"Ren X, Chen JF (2020) Caffeine and Parkinson\u2019s disease: multiple benefits and emerging mechanisms. Front Neurosci 14:602697. https:\/\/doi.org\/10.3389\/fnins.2020.602697","journal-title":"Front Neurosci"},{"key":"10160_CR55","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23212958","volume":"23","author":"M Ruggiero","year":"2022","unstructured":"Ruggiero M, Calvello R, Porro C, Messina G, Cianciulli A, Panaro MA (2022) Neurodegenerative diseases: can caffeine be a powerful ally to weaken neuroinflammation? Int J Mol Sci 23:12958. https:\/\/doi.org\/10.3390\/ijms23212958","journal-title":"Int J Mol Sci"},{"issue":"9","key":"10160_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/antiox9090902","volume":"9","author":"M Ikram","year":"2020","unstructured":"Ikram M, Park TJ, Ali T, Kim MO (2020) Antioxidant and neuroprotective effects of caffeine against Alzheimer\u2019s and Parkinson\u2019s disease: insight into the role of Nrf-2 and A2AR signaling. Antioxidants 9(9):1\u201321. https:\/\/doi.org\/10.3390\/antiox9090902","journal-title":"Antioxidants"},{"key":"10160_CR57","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.neulet.2007.12.034","volume":"432","author":"K Nakaso","year":"2008","unstructured":"Nakaso K, Ito S, Nakashima K (2008) Caffeine activates the PI3K\/Akt pathway and prevents apoptotic cell death in a Parkinson\u2019s disease model of SH-SY5Y cells. Neurosci Lett 432:146\u2013150. https:\/\/doi.org\/10.1016\/j.neulet.2007.12.034","journal-title":"Neurosci Lett"},{"key":"10160_CR58","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x13666141210215655","volume":"13","author":"S Cappelletti","year":"2015","unstructured":"Cappelletti S, Daria P, Sani G, Aromatario M (2015) Caffeine: cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol 13:71. https:\/\/doi.org\/10.2174\/1570159x13666141210215655","journal-title":"Curr Neuropharmacol"},{"key":"10160_CR59","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.ejphar.2014.11.038","volume":"747","author":"SI Uchida","year":"2015","unstructured":"Uchida SI, Soshiroda K, Okita E, Kawai-Uchida M, Mori A, Jenner P, Kanda T (2015) The adenosine A2A receptor antagonist, istradefylline enhances the anti-Parkinsonian activity of low doses of dopamine agonists in MPTP-treated common marmosets. Eur J Pharmacol 747:160\u2013165. https:\/\/doi.org\/10.1016\/j.ejphar.2014.11.038","journal-title":"Eur J Pharmacol"},{"key":"10160_CR60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.lfs.2014.01.083","volume":"101","author":"M Rivera-Oliver","year":"2014","unstructured":"Rivera-Oliver M, D\u00edaz-R\u00edos M (2014) Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: a review. Life Sci 101:1. https:\/\/doi.org\/10.1016\/j.lfs.2014.01.083","journal-title":"Life Sci"},{"key":"10160_CR61","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.652152","volume":"9","author":"DM Perez","year":"2021","unstructured":"Perez DM (2021) Current developments on the role of \u03b11-adrenergic receptors in cognition, cardioprotection, and metabolism. Front Cell Dev Biol 9:652152. https:\/\/doi.org\/10.3389\/fcell.2021.652152","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"10160_CR62","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1038\/s41598-025-30717-8","volume":"16","author":"H Cheng","year":"2026","unstructured":"Cheng H, Gao Y, Shang H, Han W, Zhang X, Gao R, Dang W, Ma Z, Liu X, Gao Y (2026) Selective antagonism of adenosine A2A receptor reduces hypobaric hypoxia-induced neuroinflammation by inhibiting cGAS-STING pathway. Sci Rep 16(1):1091. https:\/\/doi.org\/10.1038\/s41598-025-30717-8","journal-title":"Sci Rep"},{"key":"10160_CR63","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-008-9100-8","volume":"4","author":"M Cie\u015blak","year":"2008","unstructured":"Cie\u015blak M, Komoszy\u0144ski M, Wojtczak A (2008) Adenosine A2A receptors in Parkinson\u2019s disease treatment. Purinergic Signal 4:305. https:\/\/doi.org\/10.1007\/s11302-008-9100-8","journal-title":"Purinergic Signal"},{"key":"10160_CR64","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-021-00279-2","volume":"27","author":"T Ntetsika","year":"2021","unstructured":"Ntetsika T, Papathoma PE, Markaki I (2021) Novel targeted therapies for Parkinson\u2019s disease. Mol Med 27:17. https:\/\/doi.org\/10.1186\/s10020-021-00279-2","journal-title":"Mol Med"},{"key":"10160_CR65","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1212\/WNL.0000000000004003","volume":"88","author":"F Stocchi","year":"2017","unstructured":"Stocchi F, Rascol O, Hauser RA, Huyck S, Tzontcheva A, Capece R, Ho TW, Sklar P, Lines C, Michelson D, Hewitt DJ (2017) Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease. Neurology 88:2198\u20132206. https:\/\/doi.org\/10.1212\/WNL.0000000000004003","journal-title":"Neurology"},{"key":"10160_CR66","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/S1474-4422(14)70148-6","volume":"13","author":"RA Hauser","year":"2014","unstructured":"Hauser RA, Olanow CW, Kieburtz KD, Pourcher E, Docu-Axelerad A, Lew M, Kozyolkin O, Neale A, Resburg C, Meya U, Kenney C, Bandak S (2014) Tozadenant (SYN115) in patients with Parkinson\u2019s disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. Lancet Neurol 13:767\u2013776. https:\/\/doi.org\/10.1016\/S1474-4422(14)70148-6","journal-title":"Lancet Neurol"},{"key":"10160_CR67","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.brainresbull.2013.07.001","volume":"98","author":"N Jones","year":"2013","unstructured":"Jones N, Bleickardt C, Mullins D, Parker E, Hodgson R (2013) A2A receptor antagonists do not induce dyskinesias in drug-naive or L-dopa sensitized rats. Brain Res Bull 98:163\u2013169. https:\/\/doi.org\/10.1016\/j.brainresbull.2013.07.001","journal-title":"Brain Res Bull"},{"key":"10160_CR68","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16091127","volume":"16","author":"TY Chen","year":"2024","unstructured":"Chen TY, Chang YC, Yu CY, Sung WW (2024) Targeting the adenosine A2A receptor as a novel therapeutic approach for renal cell carcinoma: mechanisms and clinical trial review. Pharmaceutics 16:1127. https:\/\/doi.org\/10.3390\/pharmaceutics16091127","journal-title":"Pharmaceutics"},{"key":"10160_CR69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.irn.2023.08.001","volume":"170","author":"KA Jacobson","year":"2023","unstructured":"Jacobson KA, Suresh RR, Oliva P (2023) A2A adenosine receptor agonists, antagonists, inverse agonists and partial agonists. Int Rev Neurobiol 170:1\u201327. https:\/\/doi.org\/10.1016\/bs.irn.2023.08.001","journal-title":"Int Rev Neurobiol"},{"key":"10160_CR70","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2020.173035","author":"M Pardo","year":"2020","unstructured":"Pardo M, Paul NE, Collins-Praino LE, Salamone JD, Correa M (2020) The non-selective adenosine antagonist theophylline reverses the effects of dopamine antagonism on tremor, motor activity and effort-based decision-making. Pharmacol Biochem Behav. https:\/\/doi.org\/10.1016\/j.pbb.2020.173035","journal-title":"Pharmacol Biochem Behav"}],"container-title":["Purinergic Signalling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11302-026-10160-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11302-026-10160-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11302-026-10160-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:05:01Z","timestamp":1782363901000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11302-026-10160-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":70,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10160"],"URL":"https:\/\/doi.org\/10.1007\/s11302-026-10160-8","relation":{},"ISSN":["1573-9538","1573-9546"],"issn-type":[{"value":"1573-9538","type":"print"},{"value":"1573-9546","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"assertion":[{"value":"2 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"49"}}