Signaling pathways mediating alcohol effects

Abstract

Ethanol's effects on intracellular signaling pathways contribute to acute effects of ethanol as well as to neuroadaptive responses to repeated ethanol exposure. In this chapter we review recent discoveries that demonstrate how ethanol alters signaling pathways involving several receptor tyrosine kinases and intracellular tyrosine and serine-threonine kinases, with consequences for regulation of cell surface receptor function, gene expression, protein translation, neuronal excitability and animal behavior. We also describe recent work that demonstrates a key role for ethanol in regulating the function of scaffolding proteins that organize signaling complexes into functional units. Finally, we review recent exciting studies demonstrating ethanol modulation of DNA and histone modification and the expression of microRNAs, indicating epigenetic mechanisms by which ethanol regulates neuronal gene expression and addictive behaviors.

Fig. 1

Ethanol alters the function of membrane and intracellular enzymes. Inhibitors or up-regulators of these targets can be developed as novel therapeutics for the treatment of alcohol use disorders. Depicted are examples of such targets. Asterisks denote targets for which inhibitors are in development. Red depicts FDA-approved kinase inhibitors. Green depicts an FDA-approved medication that up-regulates the expression of a protective gene