{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T09:23:41Z","timestamp":1772789021322,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T00:00:00Z","timestamp":1714694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology\/MCTES","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology\/MCTES","award":["UIDP\/00709\/2020"],"award-info":[{"award-number":["UIDP\/00709\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology\/MCTES","award":["UI\/BD\/151025\/2021"],"award-info":[{"award-number":["UI\/BD\/151025\/2021"]}]},{"name":"Portuguese Foundation for Science and Technology\/MCTES","award":["2021.07746.BD"],"award-info":[{"award-number":["2021.07746.BD"]}]},{"name":"Portuguese Foundation for Science and Technology\/MCTES","award":["BID\/ICI-FCS\/Santander Universidades-UBI\/2019"],"award-info":[{"award-number":["BID\/ICI-FCS\/Santander Universidades-UBI\/2019"]}]},{"name":"FCT","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"FCT","award":["UIDP\/00709\/2020"],"award-info":[{"award-number":["UIDP\/00709\/2020"]}]},{"name":"FCT","award":["UI\/BD\/151025\/2021"],"award-info":[{"award-number":["UI\/BD\/151025\/2021"]}]},{"name":"FCT","award":["2021.07746.BD"],"award-info":[{"award-number":["2021.07746.BD"]}]},{"name":"FCT","award":["BID\/ICI-FCS\/Santander Universidades-UBI\/2019"],"award-info":[{"award-number":["BID\/ICI-FCS\/Santander Universidades-UBI\/2019"]}]},{"name":"UBI-Santander Totta","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"UBI-Santander Totta","award":["UIDP\/00709\/2020"],"award-info":[{"award-number":["UIDP\/00709\/2020"]}]},{"name":"UBI-Santander Totta","award":["UI\/BD\/151025\/2021"],"award-info":[{"award-number":["UI\/BD\/151025\/2021"]}]},{"name":"UBI-Santander Totta","award":["2021.07746.BD"],"award-info":[{"award-number":["2021.07746.BD"]}]},{"name":"UBI-Santander Totta","award":["BID\/ICI-FCS\/Santander Universidades-UBI\/2019"],"award-info":[{"award-number":["BID\/ICI-FCS\/Santander Universidades-UBI\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Donepezil (DNPZ) is a cholinesterase inhibitor used for the management of Alzheimer\u2019s disease (AD) and is dependent on membrane transporters such as ABCG2 to actively cross brain barriers and reach its target site of action in the brain. Located in the brain ventricles, the choroid plexus (CP) forms an interface between the cerebrospinal fluid (CSF) and the bloodstream, known as the blood\u2013CSF barrier (BCSFB). Historically, the BCSFB has received little attention as a potential pathway for drug delivery to the central nervous system (CNS). Nonetheless, this barrier is presently viewed as a dynamic transport interface that limits the traffic of molecules into and out of the CNS through the presence of membrane transporters, with parallel activity with the BBB. The localization and expression of drug transporters in brain barriers represent a huge obstacle for drug delivery to the brain and a major challenge for the development of therapeutic approaches to CNS disorders. The widespread interest in understanding how circadian clocks modulate many processes that define drug delivery in order to predict the variability in drug safety and efficacy is the next bridge to improve effective treatment. In this context, this study aims at characterizing the circadian expression of ABCG2 and DNPZ circadian transport profile using an in vitro model of the BCSFB. We found that ABCG2 displays a circadian pattern and DNPZ is transported in a circadian way across this barrier. This study will strongly impact on the capacity to modulate the BCSFB in order to control the penetration of DNPZ into the brain and improve therapeutic strategies for the treatment of AD according to the time of the day.<\/jats:p>","DOI":"10.3390\/ijms25095014","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T09:39:47Z","timestamp":1714729187000},"page":"5014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Circadian ABCG2 Expression Influences the Brain Uptake of Donepezil across the Blood\u2013Cerebrospinal Fluid Barrier"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2037-2082","authenticated-orcid":false,"given":"Andr\u00e9","family":"Furtado","sequence":"first","affiliation":[{"name":"CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, Universityof Beira Interior, Avenida Infante Dom Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5911-6521","authenticated-orcid":false,"given":"Ana Catarina","family":"Duarte","sequence":"additional","affiliation":[{"name":"CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, Universityof Beira Interior, Avenida Infante Dom Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9673-4337","authenticated-orcid":false,"given":"Ana R.","family":"Costa","sequence":"additional","affiliation":[{"name":"CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, Universityof Beira Interior, Avenida Infante Dom Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4384-8197","authenticated-orcid":false,"given":"Isabel","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, Universityof Beira Interior, Avenida Infante Dom Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6074-7825","authenticated-orcid":false,"given":"Cec\u00edlia R. A.","family":"Santos","sequence":"additional","affiliation":[{"name":"CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, Universityof Beira Interior, Avenida Infante Dom Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-8998","authenticated-orcid":false,"given":"Eugenia","family":"Gallardo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de F\u00e1rmaco-Toxicologia-UBIMedical, Universidade da Beira Interior, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5202-9858","authenticated-orcid":false,"given":"Telma","family":"Quintela","sequence":"additional","affiliation":[{"name":"CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, Universityof Beira Interior, Avenida Infante Dom Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, Instituto Polit\u00e9cnico da Guarda, 6300-559 Guarda, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,3]]},"reference":[{"key":"ref_1","first-page":"CD001190","article-title":"Donepezil for dementia due to Alzheimer\u2019s disease","volume":"6","author":"Birks","year":"2018","journal-title":"Cochrane Database Syst. 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