{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:50:24Z","timestamp":1788544224970,"version":"build-2803163510"},"reference-count":63,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,5,9]],"date-time":"2016-05-09T00:00:00Z","timestamp":1462752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004239","name":"Politechnika Pozna\u0144ska","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004239","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>\n                    The efficacy of drugs targeting the CNS is influenced by their limited brain access, which can lead to complete pharmacoresistance. Recently a tissue\u2010specific and selective upregulation of the multidrug efflux transporter ABCB1 or P\u2010glycoprotein (P\u2010gp) in the spinal cord of both patients and the mutant SOD1\u2010G93A mouse model of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease that prevalently kills motor neurons has been reported. Here, we extended the analysis of P\u2010gp expression in the SOD1\u2010G93A ALS mouse model and found that P\u2010gp upregulation was restricted to endothelial cells of the capillaries, while P\u2010gp expression was not detected in other cells of the spinal cord parenchyma such as astrocytes, oligodendrocytes, and neurons. Using both\n                    <jats:italic>in vitro<\/jats:italic>\n                    human and mouse models of the blood\u2013brain barrier (BBB), we found that mutant SOD1 astrocytes were driving P\u2010gp upregulation in endothelial cells. In addition, a significant increase in reactive oxygen species production, Nrf2 and NF\u03baB activation in endothelial cells exposed to mutant SOD1 astrocytes in both human and murine BBB models were observed. Most interestingly, astrocytes expressing FUS\u2010H517Q, a different familial ALS\u2010linked mutated gene, also drove NF\u03baB\u2010dependent upregulation of P\u2010gp. However, the pathway was not dependent on oxidative stress but rather involved TNF\u2010\u03b1 release. Overall, these findings indicated that nuclear translocation of NF\u03baB was a converging mechanism used by endothelial cells of the BBB to upregulate P\u2010gp expression in mutant SOD1\u2010linked ALS and possibly other forms of familial ALS. GLIA 2016 GLIA 2016;64:1298\u20131313\n                  <\/jats:p>","DOI":"10.1002\/glia.23003","type":"journal-article","created":{"date-parts":[[2016,5,9]],"date-time":"2016-05-09T13:15:04Z","timestamp":1462799704000},"page":"1298-1313","source":"Crossref","is-referenced-by-count":70,"title":["Astrocytes drive upregulation of the multidrug resistance transporter ABCB1 (P\u2010Glycoprotein) in endothelial cells of the blood\u2013brain barrier in mutant superoxide dismutase 1\u2010linked amyotrophic lateral sclerosis"],"prefix":"10.1002","volume":"64","author":[{"given":"Hisham","family":"Qosa","sequence":"first","affiliation":[{"name":"Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience Thomas Jefferson University 900 Walnut Street Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lichter","sequence":"additional","affiliation":[{"name":"Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience Thomas Jefferson University 900 Walnut Street Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sarlo","sequence":"additional","affiliation":[{"name":"Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience Thomas Jefferson University 900 Walnut Street Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashirekha S.","family":"Markandaiah","sequence":"additional","affiliation":[{"name":"Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience Thomas Jefferson University 900 Walnut Street Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"McAvoy","sequence":"additional","affiliation":[{"name":"Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience Thomas Jefferson University 900 Walnut Street Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Philippe","family":"Richard","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine 855 N. 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