Potential role of NF-kappaB 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-kappaB) in these crucial signal transduction processes. NF-kappaB is an inducible transcription factor detected in neurons, glia and neural stem cells. NF-kappaB was discovered by David Baltimore's laboratory as a transcription factor in lymphocytes. NF-kappaB 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-kappaB family are widely expressed by neurons, glia and neural stem cells. In the nervous system, NF-kappaB plays a crucial role in neuronal plasticity, learning, memory consolidation, neuroprotection and neurodegeneration. Recent data suggest an important role of NF-kappaB on proliferation, migration and differentiation of neural stem cells. NF-kappaB is composed of three subunits: two DNA-binding and one inhibitory subunit. Activation of NF-kappaB 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-kappaB on neural stem cells. Furthermore, we discuss the potential role of NF-kappaB within the so-called brain cancer stem cells.
Widera
Darius
D
Institut für Neurobiochemie, Universität Witten/Herdecke, Stockumer Str. 10, D-58448 Witten, Germany.
Mikenberg
Ilja
I
Kaltschmidt
Barbara
B
Kaltschmidt
Christian
C
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D008959:Models, Neurological; D016328:NF-kappa B / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha