Journal article
I kappa B kinase 2 determines oligodendrocyte loss by non-cell-autonomous activation of NF-kappa B in the central nervous system
Brain (London, England : 1878), v 134(4), pp 1184-1198
01 Apr 2011
PMID: 21310728
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The I kappa B kinase complex induces nuclear factor kappa B activation and has recently been recognized as a key player of autoimmunity in the central nervous system. Notably, I kappa B kinase/nuclear factor kappa B signalling regulates peripheral myelin formation by Schwann cells, however, its role in myelin formation in the central nervous system during health and disease is largely unknown. Surprisingly, we found that brain-specific I kappa B kinase 2 expression is dispensable for proper myelin assembly and repair in the central nervous system, but instead plays a fundamental role for the loss of myelin in the cuprizone model. During toxic demyelination, inhibition of nuclear factor kappa B activation by conditional ablation of I kappa B kinase 2 resulted in strong preservation of central nervous system myelin, reduced expression of proinflammatory mediators and a significantly attenuated glial response. Importantly, I kappa B kinase 2 depletion in astrocytes, but not in oligodendrocytes, was sufficient to protect mice from myelin loss. Our results reveal a crucial role of glial cell-specific I kappa B kinase 2/nuclear factor kappa B signalling for oligodendrocyte damage during toxic demyelination. Thus, therapies targeting I kappa B kinase 2 function in non-neuronal cells may represent a promising strategy for the treatment of distinct demyelinating central nervous system diseases.
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Details
- Title
- I kappa B kinase 2 determines oligodendrocyte loss by non-cell-autonomous activation of NF-kappa B in the central nervous system
- Creators
- Jenni Raasch - University of FreiburgNicolas Zeller - University of FreiburgGeert van Loo - European Molecular Biology LaboratoryDoron Merkler - Universitätsmedizin GöttingenAlexander Mildner - University of FreiburgDaniel Erny - University of FreiburgKlaus-Peter Knobeloch - University of FreiburgJohn R. Bethea - College Station Medical CenterAri Waisman - Johannes Gutenberg University MainzMarkus Knust - University of FreiburgDomenico Del Turco - Goethe University FrankfurtThomas Deller - Goethe University FrankfurtThomas Blank - University of FreiburgJosef Priller - Charité - Universitätsmedizin BerlinWolfgang Brueck - College Station Medical CenterManolis Pasparakis - Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated DiseasesMarco Prinz - University of Freiburg
- Publication Details
- Brain (London, England : 1878), v 134(4), pp 1184-1198
- Publisher
- Oxford Univ Press
- Number of pages
- 15
- Grant note
- R01NS051709 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Gemeinnutzige Hertie-Stiftung (GHST) PR 577/5-1; TRR43/A7; TRR43/B3; DE 551/8-1 / German Research Council [Deutsche Forschungsgemeinschaft]; German Research Foundation (DFG) BMBF; Federal Ministry of Education & Research (BMBF) 1336 / Deutsche Forschungsgemeinschaft; German Research Foundation (DFG)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Web of Science ID
- WOS:000289163300029
- Scopus ID
- 2-s2.0-79953672493
- Other Identifier
- 991020099050004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Clinical Neurology
- Neurosciences