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

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 

作者机构：College of Pharmacy and Medical Research CenterChungbuk National UniversityOsongsaengmyeong 1-roOsong-eupHeungdeok-guCheongjuChungbuk 28160Republic of Korea Department of ChemistryUtah Valley University800 W University PkwyOremUT 84058USA INISTst Co.LTD767Sinsu-roSuji-guYongin-si 16827Gyeonggi-doRepublic of Korea College of PharmacyYeungnam University280 Daehak RoadGyeonsanGyeongbuk 38541Republic of Korea 

出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)

年 卷 期：2019年第8卷第1期

页      面：317-332页

核心收录：

学科分类：0710[理学-生物学] 0402[教育学-心理学(可授教育学、理学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 1010[医学-医学技术（可授医学、理学学位）] 100214[医学-肿瘤学] 1009[医学-特种医学] 10[医学] 

基　　金：This work was supported by the National Research Foundation of Korea(NRF)grant funded by Korea government(MSIP)(No.MRC,2017R1A5A2015541) was supported by Korea Institute for Advancement of Technology(KIAT)as the research project for World Class 300 R&D(WC300 R&D,No.S2563418) 

主　　题：Bee venom phospholipase A2 Alzheimer’s disease Amyloidogenesis Neuroinflammation STAT3 

摘      要：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