Gallic acid, a histone acetyltransferase inhibitor, suppresses ss-amyloid neurotoxicity by inhibiting microglial-mediated neuroinflammation

Abstract

Scope: We examined the biological effect of gallic acid (GA) as a nuclear factor (NF)-?B acetyltransferase inhibitor on microglial-mediated beta-amyloid neurotoxicity and restorative effects on the A beta-induced cognitive dysfunction. Methods and results: The protective effects of GA on the survival of neuronal cells were assessed with an MTT assay and a co-culture system. For the co-culture experiments, both BV-2 and primary microglia cells were treated with GA prior to Ab stimulation, and conditioned media were transferred to Neuro-2A cells. The mRNA and protein levels of inflammatory cytokines in both microglia and Neuro-2A cells were assessed with real-time polymerase chain reaction and western blotting. Inhibition of nuclear factor kappa B ( NF-kB) acetylation with GA treatment resulted in reduced cytokine production in microglia cells and protection of neuronal cells from Ab-induced neurotoxicity. Furthermore, we observed a restorative effect of GA on Ab-induced cognitive dysfunction in mice with Y-maze and passive avoidance tests. Finally, we found that GA treatment efficiently blocked neuronal cell death by downregulating the expression of cytokines and the in vivo levels of NF-kB acetylation. Conclusion: These results suggest that selective inhibition of NF-kB acetylation by the histone acetyltransferase inhibitor GA is a possible therapeutic approach for alleviating the inflammatory progression of Alzheimer disease.