Alcohol protects the CNS by activating HSF1 and inducing the heat shock proteins

Although alcohol abuse and dependence have profound negative health consequences, emerging evidence suggests that exposure to low/moderate concentrations of ethanol protects multiple organs and systems. In the CNS, moderate drinking decreases the risk of dementia and Alzheimer's disease. This neuroprotection correlates with an increased expression of the heat shock proteins (HSPs). Multiple epidemiological studies revealed an inverse association between ethanol intoxication and traumatic brain injury mortality. In this case, ethanol-induced HSPs limit the inflammatory immune response diminishing cell death and improving the neurobehavioural outcome. Ethanol also protects the brain against ischemic injuries via the HSPs. In our laboratory, we demonstrated that ethanol increased the expression of several HSP genes in neurons and astrocytes by activating the transcription factor, heat shock factor 1 (HSF1). HSF1 induces HSPs that target misfolded proteins for refolding or degradation, increasing the survival chances of the cells. These data indicate that ethanol neuroprotection is mediated by the activation HSF1 and the induction of HSPs.