DJ1 Ameliorates AD-like Pathology in the Hippocampus of APP/PS1 Mice

作     者：PENG Yang Yang LI Meng Xin LI Wen Jie XUE Yuan MIAO Yu Fan WANG Yu Lin FAN Xiao Chen TANG Lu Lu SONG Han Lu ZHANG Qian LI Xing PENG Yang Yang;LI Meng Xin;LI Wen Jie;XUE Yuan;MIAO Yu Fan;WANG Yu Lin;FAN Xiao Chen;TANG Lu Lu;SONG Han Lu;ZHANG Qian;LI Xing

作者机构：Department of Nutrition and Food HygieneCollege of Public HealthZhengzhou UniversityZhengzhou 450001HenanChina The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052HenanChina 

出 版 物：《Biomedical and Environmental Sciences》 (生物医学与环境科学（英文版）)

年 卷 期：2023年第36卷第11期

页      面：1028-1044页

核心收录：

学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China[grant numbers 81872626 and 82003454] Chinese Nutrition Society-Bright Moon Seaweed Group Nutrition and Health Research Fund[grant number CNS-BMSG2020A63] Key R&D and promotion projects in Henan Province[grant number 212102310219 and 212102310110] 

主　　题：Alzheimer's disease DJ1 NRF2/HO-1 Oxidative stress AMPK/mTOR Autophagy Apoptosis 

摘      要：Objective To explore whether the protein Deglycase protein 1(DJ1)can ameliorate Alzheimer’s disease(AD)-like pathology in Amyloid Precursor Protein/Presenilin 1(APP/PS1)double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of *** Adeno-associated viral vectors(AAV)of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or *** were divided into the AD model control group(MC),AAV vector control group(NC),DJ1-overexpression group(DJ1+),and DJ1-knockdown group(DJ1-).After 21 days,the Morris water maze test,immunohistochemistry,immunofluorescence,and western blotting were used to evaluate the effects of DJ1 on *** DJ1+overexpression decreased the latency and increased the number of platform traversals in the water maze ***1-cells were cured and atrophied,and the intercellular structure was relaxed;the number of age spots and the expression of AD-related proteins were significantly ***1+increased the protein expression of Nuclear factor erythroid 2-related factor 2(NRF2),heme oxygenase-1(HO-1),light chain 3(LC3),phosphorylated AMPK(p-AMPK),and B cell lymphoma-2(BCL-2),as well as the antioxidant levels of total superoxide dismutase(T-SOD),total antioxidant capacity(T-AOC),and Glutathione peroxidase(GSH-PX),while decreasing the levels of Kelch-like hydrates-associated protein 1(Keap1),mammalian target of rapamycin(mTOR),p62/sequestosome1(p62/SQSTM1),Caspase3,and malondialdehyde(MDA).Conclusion DJ1-overexpression can ameliorate learning,memory,and AD-like pathology in APP/PS1 mice,which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.