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Bee venom phospholipase A2 ameliorates amyloidogenesis and neuroinflammation through inhibition of signal transducer and activator of transcription-3 pathway in Tg2576 mice

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Translational Neurodegeneration 2019年第1期8卷 317-332页

作者： Hyeon Joo Ham Sang-Bae Han jaesuk yun In Jun Yeo Young Wan Ham Se Hyun Kim Pil-Hoon Park Dong-Young Choi Jin Tae Hong College of Pharmacy and Medical Research Center Chungbuk National UniversityOsongsaengmyeong 1-roOsong-eupHeungdeok-guCheongjuChungbuk 28160Republic of Korea Department of Chemistry Utah Valley University800 W University PkwyOremUT 84058USA INISTst Co. LTD767Sinsu-roSuji-guYongin-si 16827Gyeonggi-doRepublic of Korea College of Pharmacy Yeungnam University280 Daehak RoadGyeonsanGyeongbuk 38541Republic of Korea

Background:Neuroinflammation and accumulation ofβ-amyloid(Aβ)play a significant role in the onset and progression of Alzheimer’s disease(AD).Our previous study demonstrated that signal transducer and activator of transcription-3(STAT3)plays a major role in neuroinflammation and ***:In the present study,we investigated the inhibitory effect of bee venom phospholipase A2(bvPLA2)on memory deficiency in Tg2576 mice,which demonstrate genetic characteristics of AD and the mechanism of its action at the cellular and animal *** in vivo study,we examined the effect of bvPLA2 on improving memory by conducting several behavioral tests with the administration of bvPLA2(1 mg/kg)to Tg2576 *** in vitro study,we examined the effect of bvPLA2 on amyloidogenesis and neuroinflammation by treating bvPLA2 on LPSactivated BV2 ***:We found that bvPLA2 alleviated memory impairment in Tg2576 mice,as demonstrated in the behavioral tests assessing *** the bvPLA2-treated group,Aβ,amyloid precursor protein(APP),and β-secretase 1(BACE1)levels and β-secretase activity were significantly *** of pro-inflammatory cytokines and inflammation-related proteins decreased in the brain of bvPLA2-treated group,whereas anti-inflammatory cytokines *** addition,bvPLA2 reduced STAT3 phosphorylation in the brains of the bvPLA2-treated *** the cellular level,bvPLA2 inhibits production of nitric oxide,pro-inflammatory cytokines,and inflammation-related proteins including ***,bvPLA2 inhibits the production of Aβin cultured BV-2 *** from the docking experiment,pull-down assay,and the luciferase assay show that bvPLA2 directly binds STAT3 and,thus,regulates gene expression ***,when the STAT3 inhibitor and bvPLA2 were administered together,the anti-amyloidogenic and anti-inflammatory effects were further enhanced than when they were administered ***:These results suggest that bvPLA2 could r

关键词： Bee venom phospholipase A2 Alzheimer’s disease Amyloidogenesis Neuroinflammation STAT3

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