Based on the promising therapeutic potentials of naturally occurring curcumin, we hypothesized that chronic curcumin administration may inhibit ethanol-induced neurodegeneration and memory impairment in mice, by regulating reactive oxygen species (ROS), toll-like receptor-4 (TLR4), and Receptor for advanced glycation end products (RAGE)-mediated neuroinflammation, while p-JNK and p-NF-kB triggered the release of cytokines and synaptic dysfunction. Here, AGER is linked to memory impairment.