TLR4-MyD88 signalling: a molecular target for alcohol actions.

Several studies implicate Toll-like receptors (TLRs) in alcohol-induced neuroinflammatory processes. The work reported by Wu et al., in this issue of the British Journal of Pharmacology, indicates that TLR4 along with its intracellular adaptor protein, MyD88, may play crucial roles in the acute actions of alcohol. The deletions of TLR4 or MyD88 gene or pharmacological inhibition of TLR4 by (+)-naloxone were able to attenuate alcohol-induced sedation, motor impairment and acute alcohol-induced increases in IkBα protein levels in the hippocampus of mice. These results clearly suggest that TLR4-MyD88 signalling may play a causal role in the mediation of the behavioural effects of acute alcohol.