Gallic acid, a histone acetyltransferase inhibitor, suppresses β-amyloid neurotoxicity by inhibiting microglial-mediated neuroinflammation
✍ Scribed by Mi-Jeong Kim; Ah-Reum Seong; Jung-Yoon Yoo; Cheng-Hao Jin; Yoo-Hyun Lee; Young Jun Kim; Jeongmin Lee; Woo Jin Jun; Ho-Geun Yoon
- Book ID
- 102515864
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 362 KB
- Volume
- 55
- Category
- Article
- ISSN
- 1613-4125
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✦ Synopsis
Abstract
Scope: We examined the biological effect of gallic acid (GA) as a nuclear factor (NF)‐κB acetyltransferase inhibitor on microglial‐mediated β‐amyloid neurotoxicity and restorative effects on the Aβ‐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 Aβ 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‐κB) acetylation with GA treatment resulted in reduced cytokine production in microglia cells and protection of neuronal cells from Aβ‐induced neurotoxicity. Furthermore, we observed a restorative effect of GA on Aβ‐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‐κB acetylation.
Conclusion: These results suggest that selective inhibition of NF‐κB acetylation by the histone acetyltransferase inhibitor GA is a possible therapeutic approach for alleviating the inflammatory progression of Alzheimer disease.