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  IKK mediates ischemia-induced neuronal death

Herrmann, O., Baumann, B., de Lorenzi, R., Muhammad, S., Zhang, W., Kleesiek, J., et al. (2005). IKK mediates ischemia-induced neuronal death. Nature Medicine, 11(12), 1322-1329. doi:10.1038/nm1323.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-725B-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-725C-5
Genre: Journal Article
Alternative Title : IKK mediates ischemia-induced neuronal death

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NatMed_11_2005_1322.pdf (Any fulltext), 492KB
 
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 Creators:
Herrmann, Oliver, Author
Baumann, Bernd, Author
de Lorenzi, Rossana, Author
Muhammad, Sajjad, Author
Zhang, Wen, Author
Kleesiek, Jens, Author
Malfertheiner, Max, Author
Köhrmann, Martin, Author
Potrovita, Ioana, Author
Maegele, Ira, Author
Beyer, Cordian, Author
Burke, James R., Author
Hasan, Mazahir T.1, Author              
Bujard, Hermann, Author
Wirth, Thomas, Author
Pasparakis, Manolis, Author
Schwaninger, Markus, Author
Affiliations:
1Department of Biomedical Optics, Max Planck Institute for Medical Research, Max Planck Society, ou_1497699              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2005-01-272005-10-052005-11-132005-12-01
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
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Title: Nature Medicine
  Other : Nat. Med.
Source Genre: Journal
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Publ. Info: New York, NY : Nature Pub. Co.
Pages: - Volume / Issue: 11 (12) Sequence Number: - Start / End Page: 1322 - 1329 Identifier: ISSN: 1078-8956
CoNE: https://pure.mpg.de/cone/journals/resource/954925606824