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


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.


CONCLUSIONS
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.
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea.
Mi-Jeong
MJ
Kim
Ah-Reum
AR
Seong
Jung-Yoon
JY
Yoo
Cheng-Hao
CH
Jin
Yoo-Hyun
YH
Lee
Young Jun
YJ
Kim
Jeongmin
J
Lee
Woo Jin
WJ
Jun
Ho-Geun
HG
Yoon
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005707:Gallic Acid / Q000494:pharmacology*; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000166:cytology / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
D016229:Amyloid beta-Peptides; D016207:Cytokines; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D005707:Gallic Acid; D051548:Histone Acetyltransferases