Alcohol is a neurotoxic compound and its abuse can induce brain damage and neurodegeneration. We have demonstrated that ethanol is capable of activating TLR4/IL-1RI receptors in astroglial and microglial cells to trigger TLR4 signaling and to produce cytokines induction (IL-1β, TNF-α, IL-6) and inflammatory mediators (iNOS, COX-2), which can lead to neuroinflammation and brain injury. Elimination of the TLR4 function abolishes most neuroinflammation and neural death (Alfonso-Loeches et al., 2010). Our recent studies have further demonstrated that neuroinflammation induced by ethanol abuse in mice is associated with demyelination and disruptions in the myelin structure and that these alterations are, in part, dependent on TLR4 signaling (Alfonso-Loeches et al., 2012).
