{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:37:53Z","timestamp":1791319073067,"version":"4.3.1"},"reference-count":81,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,9,21]]},"abstract":"<jats:p>Inactivating mutations of the NF-\u03baB essential modulator (NEMO), a key component of NF-\u03baB signaling, cause the genetic disease incontinentia pigmenti (IP). This leads to severe neurological symptoms, but the mechanisms underlying brain involvement were unclear. Here, we show that selectively deleting Nemo or the upstream kinase Tak1 in brain endothelial cells resulted in death of endothelial cells, a rarefaction of brain microvessels, cerebral hypoperfusion, a disrupted blood\u2013brain barrier (BBB), and epileptic seizures. TAK1 and NEMO protected the BBB by activating the transcription factor NF-\u03baB and stabilizing the tight junction protein occludin. They also prevented brain endothelial cell death in a NF-\u03baB\u2013independent manner by reducing oxidative damage. Our data identify crucial functions of inflammatory TAK1\u2013NEMO signaling in protecting the brain endothelium and maintaining normal brain function, thus explaining the neurological symptoms associated with IP.<\/jats:p>","DOI":"10.1084\/jem.20150165","type":"journal-article","created":{"date-parts":[[2015,9,8]],"date-time":"2015-09-08T01:49:48Z","timestamp":1441676988000},"page":"1529-1549","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":82,"title":["Brain endothelial TAK1 and NEMO safeguard the neurovascular unit"],"prefix":"10.1084","volume":"212","author":[{"given":"Dirk A.","family":"Ridder","sequence":"first","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology 1 and 2"},{"name":"Department of Radiation Oncology, University of L\u00fcbeck, 23562 L\u00fcbeck, Germany 1 and 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