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Home/Research/Paper Chase/Ethanol inhibits neuronal differentiation by disrupting activity-dependent neuroprotective protein signaling.
Ethanol inhibits neuronal differentiation by disrupting activity-dependent neuroprotective protein signaling.
Proc. Natl. Acad. Sci. U.S.A..Dec 16, 2008;105(50):19962-7.
Chen S, Charness ME.
VA Boston Healthcare System, 1400 VFW Parkway, West Roxbury, MA 02132, USA.
The mechanisms by which ethanol damages the developing and adult central nervous system (CNS) remain unclear. Activity-dependent neuroprotective protein (ADNP) is a glial protein that protects the CNS against a wide array of insults and is critical for CNS development. NAPVSIPQ (NAP), a potent active fragment of ADNP, potentiated axon outgrowth in cerebellar granule neurons by activating the sequential tyrosine phosphorylation of Fyn kinase and the scaffold protein Crk-associated substrate (Cas). Pharmacological inhibition of Fyn kinase or expression of a Fyn kinase siRNA abolished NAP-mediated axon outgrowth. Concentrations of ethanol attained after social drinking blocked NAP-mediated axon outgrowth (IC(50) = 17 mM) by inhibiting NAP activation of Fyn kinase and Cas. These findings identify a mechanism for ADNP regulation of glial-neuronal interactions in developing cerebellum and a pathogenesis of ethanol neurotoxicity.