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

Authors
 Mi-Jeong Kim ; Ah-Reum Seong ; Ho-Geun Yoon ; Woo Jin Jun ; Jeongmin Lee ; Young Jun Kim ; Yoo-Hyun Lee ; Cheng-Hao Jin ; Jung-Yoon Yoo 
Citation
 Molecular Nutrition & Food Research, Vol.55(12) : 1798~1808, 2011 
Journal Title
 Molecular Nutrition & Food Research 
ISSN
 1613-4125 
Issue Date
2011
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
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/94647
DOI
10.1002/mnfr.201100262
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Biochemistry & Molecular Biology
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
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Link
 http://onlinelibrary.wiley.com/doi/10.1002/mnfr.201100262/abstract
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