Details

Autor(en) / Beteiligte

• Ridder, Dirk A
• Wenzel, Jan
• Müller, Kristin
• Töllner, 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
• Bedell, Barry J
• Pasparakis, Manolis
• Balschun, Detlef
• D'Hooge, Rudi
• Löscher, Wolfgang
• Hamel, Edith
• Schwaninger, Markus

Titel

Brain endothelial TAK1 and NEMO safeguard the neurovascular unit

Ist Teil von

• The Journal of experimental medicine, 2015-09, Vol.212 (10), p.1529-1549

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Inactivating mutations of the NF-κB essential modulator (NEMO), a key component of NF-κB 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-κB and stabilizing the tight junction protein occludin. They also prevented brain endothelial cell death in a NF-κB-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.