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Ethanol inhibits neuronal differentiation by disrupting activity-dependent neuroprotective protein signaling.

Authors: Chen, S  Charness, ME 
Citation: Chen S and Charness ME, Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19962-7. Epub 2008 Dec 1.
Pubmed: (View Article at PubMed) PMID:19047645
DOI: Full-text: DOI:10.1073/pnas.0807758105

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.

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CRRD Object Information
CRRD ID: 2312772
Created: 2009-09-02
Species: All species
Last Modified: 2009-09-02
Status: ACTIVE



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