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TNF-α/NF-κB Signaling in the CNS: Possible Connection to EPHB2

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Abstract

Tumor necrosis factor-alpha, TNF-α, is a cytokine that is a well-known factor in multiple disease conditions and is recognized for its major role in central nervous system signaling. TNF-α signaling is most commonly associated with neurotoxicity, but in some conditions it has been found to be neuroprotective. TNF-α has long been known to induce nuclear factor-kappa B, NF-κB, signaling by, in most cases, translocating the p65 (RelA) DNA binding factor to the nucleus. p65 is a key member of NF-κB, which is well established as a family of transcription factors that regulates many signaling events, including growth and process development, in neuronal cell populations. NF-κB has been shown to affect both the receiving aspect of neuronal signaling events in dendritic development as well as the sending of neuronal signals in axonal development. In both cases, NK-κB functions as a promoter and/or inhibitor of growth, depending on the environmental conditions and signaling cascade. In addition, NF-κB is involved in memory formation or neurogenesis, depending on the region of the brain in which the signaling occurs. The ephrin (Eph) receptor family represents a subfamily of receptor tyrosine kinases, RTKs, which received much attention due to its potential involvement in neuronal cell health and function. There are two subsets of ephrin receptors, Eph A and Eph B, each with distinct functions in cardiovascular and skeletal development and axon guidance and synaptic plasticity. The presence of multiple binding sites for NF-κB within the regulatory region of EphB2 gene and its potential regulation by NF-κB pathway suggests that TNF-α may modulate EphB2 via NF-κB and that this may contribute to the neuroprotective activity of TNF-α.

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Acknowledgments

We thank past and present members of the Center for Neurovirology for their insightful discussion and sharing of ideas and reagents. This work was supported by a grant awarded by the NIH to KK.

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The authors declare that they have no conflict of interest.

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  1. Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Room 741 MERB, 3500N. Broad Street, Philadelphia, PA, 19140, USA

    Paul D. Pozniak, Martyn K. White & Kamel Khalili

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  1. Paul D. Pozniak
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  2. Martyn K. White
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Correspondence to Kamel Khalili.

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Pozniak, P.D., White, M.K. & Khalili, K. TNF-α/NF-κB Signaling in the CNS: Possible Connection to EPHB2. J Neuroimmune Pharmacol 9, 133–141 (2014). https://doi.org/10.1007/s11481-013-9517-x

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