Potential role of NF-κB in adult neural stem cells: the underrated steersman?

Neural stem cells are precursors of neurons and glial cells. During brain development, these cells proliferate, migrate and differentiate into specific lineages. Recently neural stem cells within the adult central nervous system were identified. Informations are now emerging about regulation of stem cell proliferation, migration and differentiation by numerous soluble factors such as chemokines and cytokines. However, the signal transduction mechanisms downstream of these factors are less clear.Here, we review potential evidences for a novel central role of the transcription factor nuclear factor kappa B (NF-κB) in these crucial signal transduction processes.NF-κB is an inducible transcription factor detected in neurons, glia and neural stem cells. NF-κB was discovered by David Baltimore's laboratory as a transcription factor in lymphocytes [Nabel, G., Baltimore, D., 1987. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature 326 (6114), 711–713]. NF-κB is involved in many biological processes such as inflammation and innate immunity, development, apoptosis and anti-apoptosis. It has been recently shown that members of the NF-κB family are widely expressed by neurons, glia and neural stem cells [Kaltschmidt, B., Kaltschmidt, C., 2003. NF-κB in the nervous system. In: R. Beyaert (Ed.), Nuclear Factor κB. Regulation and Role in Disease. Kluwer Academic Publishers, pp. 375–394; Denis-Donini, S., Caprini, A., et al., 2005. Members of the NF-κB family expressed in zones of active neurogenesis in the postnatal and adult mouse brain. Brain Res. Dev. Brain Res. 154 (1), 81–89]. In the nervous system, NF-κB plays a crucial role in neuronal plasticity, learning, memory consolidation, neuroprotection and neurodegeneration, for review, see [Kaltschmidt, B., Widera, D., et al., 2005. Signaling via NF-kappaB in the nervous system. Biochim. Biophys. Acta]. Recent data suggest an important role of NF-κB on proliferation, migration and differentiation of neural stem cells.NF-κB is composed of three subunits: two DNA-binding and one inhibitory subunit. Activation of NF-κB takes place in the cytoplasm and results in degradation of the inhibitory subunit, thus enabling the nuclear import of the DNA-binding subunits. Within the nucleus, several target genes could be activated.In this review, we suggest a model explaining the multiple action of NF-κB on neural stem cells. Furthermore, we discuss the potential role of NF-κB within the so-called brain cancer stem cells.