4.6 Review

The Role of Toll and Nonnuclear NF-?B Signaling in the Response to Alcohol

Journal

CELLS
Volume 12, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/cells12111508

Keywords

alcohol; addiction; innate immune system; neuroimmune; Drosophila; NF-kappa B; Toll

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An understanding of neuroimmune signaling is crucial for understanding alcohol addiction and its damaging effects. The neuroimmune system can influence neural activity through gene expression changes. This review explores the role of CNS Toll-like receptor (TLR) signaling in alcohol response. It also highlights findings in Drosophila that suggest TLR signaling pathways can impact behavior beyond commonly recognized mechanisms, such as TLRs substituting for neurotrophin receptors and non-genomic actions of NF-κB in alcohol responsivity.
An understanding of neuroimmune signaling has become central to a description of how alcohol causes addiction and how it damages people with an AUD. It is well known that the neuroimmune system influences neural activity via changes in gene expression. This review discusses the roles played by CNS Toll-like receptor (TLR) signaling in the response to alcohol. Also discussed are observations in Drosophila that show how TLR signaling pathways can be co-opted by the nervous system and potentially shape behavior to a far greater extent and in ways different than generally recognized. For example, in Drosophila, TLRs substitute for neurotrophin receptors and an NF-?B at the end of a TLR pathway influences alcohol responsivity by acting non-genomically.

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