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  • Title: Constitutive nuclear factor-kappa B activity is required for central neuron survival.
    Author: Bhakar AL, Tannis LL, Zeindler C, Russo MP, Jobin C, Park DS, MacPherson S, Barker PA.
    Journal: J Neurosci; 2002 Oct 01; 22(19):8466-75. PubMed ID: 12351721.
    Abstract:
    The function of nuclear factor (NF)-kappaB within the developing and mature CNS is controversial. We have generated transgenic mice to reveal NF-kappaB transcriptional activity in vivo. As expected, constitutive NF-kappaB activity was observed within immune organs, and tumor necrosis factor-inducible NF-kappaB activity was present in mesenchymal cells. Intriguingly, NF-kappaB activity was also prominent in the CNS throughout development, especially within neocortex, olfactory bulbs, amygdala, and hippocampus. NF-kappaB in the CNS was restricted to neurons and blocked by overexpression of dominant-negative NF-kappaB-inducible kinase or the IkappaBalphaM super repressor. Blocking endogenous neuronal NF-kappaB activity in cortical neurons using recombinant adenovirus induced neuronal death, whereas induction of NF-kappaB activity increased levels of anti-apoptotic proteins and was strongly neuroprotective. Together, these data demonstrate a physiological role for NF-kappaB in maintaining survival of central neurons.
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