Ridder, Dirk A., Wenzel, Jan, Mueller, Kristin, Toellner, Kathrin, Tong, Xin-Kang, Assmann, Julian C., Stroobants, Stijn, Weber, Tobias, Niturad, Cristina, Fischer, Lisanne, Lembrich, Beate, Wolburg, Hartwig, Grand'Maison, Marilyn, Papadopoulos, Panayiota, Korpos, Eva, Truchetet, Francois, Rades, Dirk, Sorokin, Lydia M., Schmidt-Supprian, Marc ORCID: 0000-0002-8543-6166, Bedell, Barry J., Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Balschun, Detlef, D'Hooge, Rudi, Loescher, Wolfgang, Hamel, Edith and Schwaninger, Markus ORCID: 0000-0002-4510-9718 (2015). Brain endothelial TAK1 and NEMO safeguard the neurovascular unit. J. Exp. Med., 212 (10). S. 1529 - 1550. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-9538

Full text not available from this repository.

Abstract

Inactivating mutations of the NF-kappa B essential modulator (NEMO), a key component of NF-kappa B 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-brain barrier (BBB), and epileptic seizures. TAK1 and NEMO protected the BBB by activating the transcription factor NF-kappa B and stabilizing the tight junction protein occludin. They also prevented brain endothelial cell death in a NF-kappa B-independent manner by reducing oxidative damage. Our data identify crucial functions of inflammatory TAK1-NEMO signaling in protecting the brain endothelium and maintaining normal brain function, thus explaining the neurological symptoms associated with IP.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ridder, Dirk A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wenzel, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, KristinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toellner, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tong, Xin-KangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assmann, Julian C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stroobants, StijnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niturad, CristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, LisanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lembrich, BeateUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolburg, HartwigUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grand'Maison, MarilynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Papadopoulos, PanayiotaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korpos, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Truchetet, FrancoisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rades, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sorokin, Lydia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt-Supprian, MarcUNSPECIFIEDorcid.org/0000-0002-8543-6166UNSPECIFIED
Bedell, Barry J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
Balschun, DetlefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
D'Hooge, RudiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loescher, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamel, EdithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwaninger, MarkusUNSPECIFIEDorcid.org/0000-0002-4510-9718UNSPECIFIED
URN: urn:nbn:de:hbz:38-392780
DOI: 10.1084/jem.20150165
Journal or Publication Title: J. Exp. Med.
Volume: 212
Number: 10
Page Range: S. 1529 - 1550
Date: 2015
Publisher: ROCKEFELLER UNIV PRESS
Place of Publication: NEW YORK
ISSN: 1540-9538
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NF-KAPPA-B; INCONTINENTIA PIGMENTI; ALZHEIMERS-DISEASE; MOUSE MODEL; BARRIER PERMEABILITY; INHIBITION PROTECTS; OXIDATIVE STRESS; AMYLOID-BETA; MICE; CELLSMultiple languages
Immunology; Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/39278

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item