RGD Reference Report - IKK mediates ischemia-induced neuronal death. - Rat Genome Database

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IKK mediates ischemia-induced neuronal death.

Authors: Herrmann, O  Baumann, B  De Lorenzi, R  Muhammad, S  Zhang, W  Kleesiek, J  Malfertheiner, M  Kohrmann, M  Potrovita, I  Maegele, I  Beyer, C  Burke, JR  Hasan, MT  Bujard, H  Wirth, T  Pasparakis, M  Schwaninger, M 
Citation: Herrmann O, etal., Nat Med. 2005 Dec;11(12):1322-9. Epub 2005 Nov 13.
RGD ID: 10045955
Pubmed: PMID:16286924   (View Abstract at PubMed)
DOI: DOI:10.1038/nm1323   (Journal Full-text)

The IkappaB kinase complex IKK is a central component of the signaling cascade that controls NF-kappaB-dependent gene transcription. So far, its function in the brain is largely unknown. Here, we show that IKK is activated in a mouse model of stroke. To investigate the function of IKK in brain ischemia we generated mice that contain a targeted deletion of Ikbkb (which encodes IKK2) in mouse neurons and mice that express a dominant inhibitor of IKK in neurons. In both lines, inhibition of IKK activity markedly reduced infarct size. In contrast, constitutive activation of IKK2 enlarged the infarct size. A selective small-molecule inhibitor of IKK mimicked the effect of genetic IKK inhibition in neurons, reducing the infarct volume and cell death in a therapeutic time window of 4.5 h. These data indicate a key function of IKK in ischemic brain damage and suggest a potential role for IKK inhibitors in stroke therapy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
middle cerebral artery infarction treatmentISOIkbkb (Mus musculus)10045955; 10045955 RGD 
middle cerebral artery infarction treatmentIMP 10045955 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ikbkb  (inhibitor of nuclear factor kappa B kinase subunit beta)

Genes (Mus musculus)
Ikbkb  (inhibitor of kappaB kinase beta)

Genes (Homo sapiens)
IKBKB  (inhibitor of nuclear factor kappa B kinase subunit beta)


Additional Information