RGD Reference Report - Brain endothelial TAK1 and NEMO safeguard the neurovascular unit. - Rat Genome Database

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Brain endothelial TAK1 and NEMO safeguard the neurovascular unit.

Authors: Ridder, DA  Wenzel, J  Muller, K  Tollner, K  Tong, XK  Assmann, JC  Stroobants, S  Weber, T  Niturad, C  Fischer, L  Lembrich, B  Wolburg, H  Grand'Maison, M  Papadopoulos, P  Korpos, E  Truchetet, F  Rades, D  Sorokin, LM  Schmidt-Supprian, M  Bedell, BJ  Pasparakis, M  Balschun, D  D'Hooge, R  Loscher, W  Hamel, E  Schwaninger, M 
Citation: Ridder DA, etal., J Exp Med. 2015 Sep 21;212(10):1529-49. doi: 10.1084/jem.20150165. Epub 2015 Sep 7.
RGD ID: 11074637
Pubmed: PMID:26347470   (View Abstract at PubMed)
PMCID: PMC4577837   (View Article at PubMed Central)
DOI: DOI:10.1084/jem.20150165   (Journal Full-text)

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




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
MAP3K7Humanbrain edema  ISOMap3k7 (Mus musculus) RGD 
Map3k7Ratbrain edema  ISOMap3k7 (Mus musculus) RGD 
Map3k7Mousebrain edema  IMP  RGD 


Genes (Rattus norvegicus)
Map3k7  (mitogen activated protein kinase kinase kinase 7)

Genes (Mus musculus)
Map3k7  (mitogen-activated protein kinase kinase kinase 7)

Genes (Homo sapiens)
MAP3K7  (mitogen-activated protein kinase kinase kinase 7)