文献类型：期刊文献

英文题名：Rescue of cognitive deficits in APP/PS1 mice by accelerating the aggregation of beta-amyloid peptide

作者：Zhang, Jian-Xiang[1];Lai, Yi-Hui[1];Mi, Pan-Ying[1];Dai, Xue-Ling[2];Zhang, Ran[1];Zhang, Zhan-Jun[3];Zhang, Shu-Juan[4];Zhang, Xi-Wen[5];Zhang, Xi-Yan[1];Yang, Bing-Yu[1];Cui, Dong-Mei[6];Zhang, Chen[7];Zhao, Chang-Qi[1];Dou, Fei[1,3]

第一作者：Zhang, Jian-Xiang

通讯作者：Zhao, CQ[1];Dou, F[1];Dou, F[2];Zhang, C[3]

机构：[1]Beijing Normal Univ, Coll Life Sci, Beijing Key Lab Genet Engn Drugs & Biotechnol, Beijing 100875, Peoples R China;[2]Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, Beijing 100191, Peoples R China;[3]Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China;[4]Peking Univ, China Japan Friendship Sch Clin Med, Beijing 100029, Peoples R China;[5]161 Middle Sch, Beijing 100006, Peoples R China;[6]Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310014, Zhejiang, Peoples R China;[7]Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China

第一机构：Beijing Normal Univ, Coll Life Sci, Beijing Key Lab Genet Engn Drugs & Biotechnol, Beijing 100875, Peoples R China

通讯机构：[1]corresponding author), Beijing Normal Univ, Coll Life Sci, Beijing Key Lab Genet Engn Drugs & Biotechnol, Beijing 100875, Peoples R China;[2]corresponding author), Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China;[3]corresponding author), Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China.

年份：2019

卷号：11

期号：1

外文期刊名：ALZHEIMERS RESEARCH & THERAPY

收录：;Scopus(收录号：2-s2.0-85076850323);WOS:【SCI-EXPANDED(收录号:WOS:000512735800002)】；

基金：This work was supported by the National Major Scientific and Technological Special Project for "Significant New Drugs Development" (2013ZX09103001019) and the Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning.

语种：英文

外文关键词：Alzheimer's disease; beta-Amyloid; Oligomers; Globulomers; Flavonoid

摘要：Background Brain amyloid deposition is one of the main pathological characteristics of Alzheimer's disease (AD). Soluble oligomers formed during the process that causes beta-amyloid (A beta) to aggregate into plaques are considered to have major neurotoxicity. Currently, drug development for the treatment of Alzheimer's disease has encountered serious difficulties. Our newly proposed solution is to accelerate the aggregation of A beta to reduce the amount of cytotoxic A beta oligomers in brain tissue. This strategy differs from the existing strategy of reducing the total A beta content and the number of amyloid plaques. Method In this study, we screened a small library and found that a flavonoid compound (ZGM1) promoted the aggregation of beta-amyloid (A beta). We further verified the binding of ZGM1 to A beta 42 using a microscale thermophoresis (MST) assay. Subsequently, we used dot blotting (DB), transmission electron microscopy (TEM), and thioflavin T fluorescence (ThT) measurements to study the aggregation of A beta under the influence of ZGM1. By using cell experiments, we determined whether ZGM1 can inhibit the cytotoxicity of A beta. Finally, we studied the protective effects of ZGM1 on cognitive function in APPswe/PS1 mice via behavioral experiments and measured the number of plaques in the mouse brain by thioflavin staining. Results ZGM1 can bind with A beta directly and mediate a new A beta assembly process to form reticular aggregates and reduce the amount of A beta oligomers. Animal experiments showed that ZGM1 can significantly improve cognitive dysfunction and that A beta plaque deposition in the brain tissue of mice in the drug-administered group was significantly increased. Conclusion Our research suggests that promoting A beta aggregation is a promising treatment method for AD and deserves further investigation.