Schematic representation of the hypothesized role of HIF-1α in alcohol-induced neurological damage.

<p>The poor diet of chronic alcohol consumers and subsequent loss of intestinal thiamine transport contributes to TD in these patients. We have demonstrated that TD induces HIF-1α signaling and pro-apoptotic/inflammatory HIF-1α target genes such as MCP1, BNIP3, Nix and Noxa in astrocytes. Independent of TD, ethanol metabolism by CYP2E1 leads to an increase in oxygen consumption resulting in the development of a hypoxic microenvironment and an increase in ROS. In astrocytes, this may also lead to stabilization of HIF-1α and subsequent cellular death. Overall, this would suggest that apoptosis in either uncomplicated alcoholism or in conjunction with TD is mediated by a HIF-1α response to induce pro-apoptotic/inflammatory signaling, as observed in ischemic disease.