{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:54:54Z","timestamp":1778741694832,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:00:00Z","timestamp":1592265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada","award":["498383"],"award-info":[{"award-number":["498383"]}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Folates are important for neurodevelopment and cognitive function. Folate transport across biological membranes is mediated by three major pathways: folate receptor alpha (FR\u03b1), proton\u2010coupled folate transporter (PCFT), and reduced folate carrier (RFC). Brain folate transport primarily occurs at the choroid plexus through FR\u03b1 and PCFT; inactivation of these transport systems results in suboptimal folate levels in the cerebrospinal fluid (CSF) causing childhood neurological disorders. Our group has reported that upregulation of RFC at the blood\u2010brain barrier (BBB) through interactions with specific transcription factors, that is, vitamin D receptor (VDR) could increase brain folate delivery. This study investigates the role of nuclear respiratory factor 1 (NRF\u20101) in the regulation of RFC at the BBB. Activation of NRF\u20101\/PGC\u20101\u03b1 signaling through treatment with its specific ligand, pyrroloquinoline quinone (PQQ), significantly induced RFC expression and transport activity in hCMEC\/D3 cells. In contrast, transfection with NRF\u20101 or PGC\u20101\u03b1 targeting siRNA downregulated RFC functional expression in the same cell system. Applying chromatin immunoprecipitation (ChIP) assay, we further demonstrated that PQQ treatment increased NRF\u20101 binding to putative NRF\u20101 binding sites within the\n                    <jats:italic>SLC19A1<\/jats:italic>\n                    promoter, which encodes for RFC. Additionally, in vivo treatment of wild type mice with PQQ\u2010induced RFC expression in isolated mouse brain capillaries. Together, these findings demonstrate that NRF\u20101\/PGC\u20101\u03b1 activation by PQQ upregulates RFC functional expression at the BBB and could potentially enhance brain folate uptake.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000239rr","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T14:17:34Z","timestamp":1596032254000},"page":"10516-10530","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Nuclear respiratory factor 1 (NRF\u20101) upregulates the expression and function of reduced folate carrier (RFC) at the blood\u2010brain barrier"],"prefix":"10.1096","volume":"34","author":[{"given":"Camille","family":"Alam","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Leslie Dan Faculty of Pharmacy University of Toronto Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Md. 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