中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (7): 707-711.doi: 10.4103/1673-5374.131572

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

Role of nuclear factor kappa B in central nervous system regeneration

  

  • 收稿日期:2014-04-09 出版日期:2014-04-15 发布日期:2014-04-15

Role of nuclear factor kappa B in central nervous system regeneration

Christian Engelmann, Falk Weih, Ronny Haenold   

  1. Leibniz Institute for Age Research-Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany
  • Received:2014-04-09 Online:2014-04-15 Published:2014-04-15
  • Contact: Ronny Haenold, Leibniz Institute for Age Research – Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany, rhaenold@fli-leibniz.de.
  • Supported by:

    This work was supported by the Leibniz Association, Germany, and the VELUX Foundation, Switzerland.

Abstract:

Activation of nuclear factor kappa B (NF-κB) is a hallmark of various central nervous system (CNS) pathologies. Neuron-specific inhibition of its transcriptional activator subunit RelA, also referred to as p65, promotes neuronal survival under a range of conditions, i.e., for ischemic or excitotoxic insults. In macro- and microglial cells, post-lesional activation of NF-κB triggers a growth-permissive program which contributes to neural tissue inflammation, scar formation, and the expression of axonal growth inhibitors. Intriguingly, inhibition of such inducible NF-κB in the neuro-glial compartment, i.e., by genetic ablation of RelA or overexpression of a transdominant negative mutant of its upstream regulator IκBα, significantly enhances functional recovery and promotes axonal regeneration in the mature CNS. By contrast, depletion of the NF-κB subunit p50, which lacks transcriptional activator function and acts as a transcriptional repressor on its own, causes precocious neuronal loss and exacerbates axonal degeneration in the lesioned brain. Collectively, the data imply that NF-κB orchestrates a multicellular program in which κB-dependent gene expression establishes a growth-repulsive terrain within the post-lesioned brain that limits structural regeneration of neuronal circuits. Considering these subunit-specific functions, interference with the NF-κB pathway might hold clinical potentials to improve functional restoration following traumatic CNS injury.

Key words: nuclear factor kappa B, RelA, p65, p50, central nervous system injury, axonal regeneration, neural regeneration