{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T01:31:00Z","timestamp":1777771860238,"version":"3.51.4"},"reference-count":102,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N42A660301 (SCC) and the Research Chair Grant(NC)"],"award-info":[{"award-number":["N42A660301 (SCC) and the Research Chair Grant(NC)"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["CMU Excellent Center award(NC)"],"award-info":[{"award-number":["CMU Excellent Center award(NC)"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>With a focus on the discrepancy between preclinical and clinical findings, this review will gather comprehensive information about the effects of calcineurin inhibitors (CNI) on cognitive function and related brain pathology from <jats:italic>in vitro<\/jats:italic>, <jats:italic>in vivo<\/jats:italic>, and clinical studies. We also summarize the potential mechanisms that underlie the pathways related to CNI\u2010induced cognitive impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We systematically searched articles in PubMed using keywords \u2018calcineurin inhibitor*\u2019 and \u2018cognition\u2019 to identify related articles, which the final list pertaining to underlying mechanisms of CNI on cognition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Several studies have reported an association between calcineurin and the neuropathology of Alzheimer\u2019s disease (AD). AD is the most common neurocognitive disorder associated with amyloid plaques and neurofibrillary tangles in the brain, leading to cognitive impairment. CNI, including tacrolimus and cyclosporin A, are commonly prescribed for patients with transplantation of solid organs such as kidney, liver, or heart, those drugs are currently being used as long\u2010term immunosuppressive therapy. Although preclinical models emphasize the favorable effects of CNI on the restoration of brain pathology due to the impacts of calcineurin on the alleviation of amyloid\u2010beta deposition and tau hyperphosphorylation, or rescuing synaptic and mitochondrial functions, treatment\u2010related neurotoxicity, resulting in cognitive dysfunctions has been observed in clinical settings of patients who received CNI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Inconsistent results of CNI on cognition from clinical studies have been observed due to impairment of the blood\u2010brain barrier, neuroinflammation mediated by reactive oxygen species, and alteration in mitochondrial fission, and extended research is required to confirm its promising use in cognitive impairment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.14161","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T12:50:53Z","timestamp":1715777453000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["How calcineurin inhibitors affect cognition"],"prefix":"10.1111","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0556-541X","authenticated-orcid":false,"given":"Kitti","family":"Thiankhaw","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, Faculty of Medicine Chiang Mai University  Chiang Mai Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-718X","authenticated-orcid":false,"given":"Nipon","family":"Chattipakorn","sequence":"additional","affiliation":[{"name":"Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine Chiang Mai University  Chiang Mai Thailand"},{"name":"Center of Excellence in Cardiac Electrophysiology Research Chiang Mai University  Chiang Mai Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1677-7052","authenticated-orcid":false,"given":"Siripron C.","family":"Chattipakorn","sequence":"additional","affiliation":[{"name":"Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine Chiang Mai University  Chiang Mai Thailand"},{"name":"Center of Excellence in Cardiac Electrophysiology Research Chiang Mai University  Chiang Mai Thailand"},{"name":"Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry Chiang Mai University  Chiang Mai Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2017.01.005"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00195"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-014-0158-7"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.4.1483"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-020-00636-4"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8086-2"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2010.00645.x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02717-y"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22445"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2709"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.12.037"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-019-00712-z"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002274"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12599"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.24984"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2019.101248"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra040223"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16074-2"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S350939"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2010.09.011"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00042.2018"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18010144"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.01.018"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.12.004"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007427200"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2008.00434.x"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07402.x"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2011.2043"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12507"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-015-0166-2"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-014-0327-5"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07447.x"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv024"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27061816"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13416"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b16-00350"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0877-17.2017"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-100261"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174310"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12959"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-013-8241-2"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109786"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-022-00334-w"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00157"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2020.566615"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2021.118320"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000000811"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.11.014"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1992.tb10036.x"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2018.05.010"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0227-12.2012"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.10.004"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2016.12.018"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-021-08675-x"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0b013e32836546db"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180903"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(03)00502-7"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205013666160404120542"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10082125"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00428"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2019.107032"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20031107"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-020-05751-1"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2018.12.006"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/1-4020-7949-4_10"},{"issue":"2","key":"e_1_2_12_69_1","first-page":"130","article-title":"Intra\u2010CA1 administration of FK\u2010506 (tacrolimus) in rat impairs learning and memory in an inhibitory avoidance paradigm","volume":"18","author":"Hadjiasgary A","year":"2015","journal-title":"Iran J Basic Med Sci"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-023-01068-6"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00298-8"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00361-6"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1128521"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0361-21.2021"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20133210"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4557-4096-3.00017-9"},{"issue":"1","key":"e_1_2_12_77_1","first-page":"7","article-title":"NFATs and Alzheimer's disease","volume":"2","author":"Abdul HM","year":"2010","journal-title":"Mol Cell Pharmacol"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150065"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-021-05398-w"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-051116-052358"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00199"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1097\/TXD.0000000000000658"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15256"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2006.03.009"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.949763"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2006.02.005"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.34067\/KID.0002052020"},{"issue":"11","key":"e_1_2_12_88_1","first-page":"1946","article-title":"Pharmacokinetic animal PET study of FK506 as a potent neuroprotective agent","volume":"45","author":"Murakami Y","year":"2004","journal-title":"J Nucl Med"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1124\/mi.4.2.7"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.12927"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0000000000000281"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-230780"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2323-12.2012"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6439-11.2012"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.069099"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23011"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1080\/13803395.2011.595396"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfad239"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12553"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229759"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.12.034"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.3906\/sag-2008-291"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2008.02480.x"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.14161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T09:16:45Z","timestamp":1717838205000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.14161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":102,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/apha.14161"],"URL":"https:\/\/doi.org\/10.1111\/apha.14161","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,15]]},"assertion":[{"value":"2023-11-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14161"}}