Article Microglial apolipoprotein E particles contribute to neuronal senescence and synaptotoxicity

作者全名：Wang, Na; Cai, Lujian; Pei, Xinyu; Lin, Zhihao; Huang, Lihong; Liang, Chensi; Wei, Min; Shao, Lin; Guo, Tiantian; Huang, Fang; Luo, Hong; Zheng, Honghua; Chen, Xiao-fen; Leng, Lige; Zhang, Yun-wu; Zhang, Jie; Guo, Kai; Wang, Xin; Wang, Zhanxiang; Zhang, Hongsheng; Zhao, Yingjun; Xu, Huaxi

作者地址：[Wang, Na; Cai, Lujian; Pei, Xinyu; Lin, Zhihao; Huang, Lihong; Liang, Chensi; Wei, Min; Shao, Lin; Guo, Tiantian; Luo, Hong; Zheng, Honghua; Chen, Xiao-fen; Leng, Lige; Zhang, Yun-wu; Zhang, Jie; Wang, Zhanxiang; Zhao, Yingjun; Xu, Huaxi] Xiamen Univ, Affiliated Hosp 1, Sch Med,Inst Neurosci,Ctr Brain Sci, Fujian Prov Key Lab Neurodegenerat Dis & Aging Res, Xiamen 361005, Fujian, Peoples R China; [Huang, Lihong; Wang, Xin] Xiamen Univ, State Key Lab Cellular Stress Biol, Xiamen 361102, Peoples R China; [Huang, Fang; Zhang, Hongsheng; Xu, Huaxi] Chongqing Med Univ, Inst Brain Sci & Dis, Chongqing 400016, Peoples R China; [Huang, Fang; Guo, Kai; Zhang, Hongsheng] Minist Educ, Key Lab Major Brain Dis & Aging Res, Chongqing 400016, Peoples R China

通信作者：Wang, ZX; Zhao, YJ (通讯作者)，Xiamen Univ, Affiliated Hosp 1, Sch Med,Inst Neurosci,Ctr Brain Sci, Fujian Prov Key Lab Neurodegenerat Dis & Aging Res, Xiamen 361005, Fujian, Peoples R China.; Zhang, HS (通讯作者)，Chongqing Med Univ, Inst Brain Sci & Dis, Chongqing 400016, Peoples R China.; Zhang, HS (通讯作者)，Minist Educ, Key Lab Major Brain Dis & Aging Res, Chongqing 400016, Peoples R China.

来源：ISCIENCE

ESI学科分类：　

WOS号：WOS:001248536900003

JCR分区：Q1

影响因子：4.6

年份：2024

卷号：27

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要：Apolipoprotein E (apoE) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Microglia exhibit a substantial upregulation of apoE in AD -associated circumstances, despite astrocytes being the primary source of apoE expression and secretion in the brain. Although the role of astrocytic apoE in the brain has been extensively investigated, it remains unclear that whether and how apoE particles generated from astrocytes and microglia differ in biological characteristic and function. Here, we demonstrate the differences in size between apoE particles generated from microglia and astrocytes. Microglial apoE particles impair neurite growth and synapses, and promote neuronal senescence, whereas depletion of GPNMB (glycoprotein non -metastatic melanoma protein B) in microglial apoE particles mitigated these deleterious effects. In addition, human APOE4-expressing microglia are more neurotoxic than APOE3-bearing microglia. For the first time, these results offer concrete evidence that apoE particles produced by microglia are involved in neuronal senescence and toxicity.

基金机构：Xiamen University; Lingang Laboratory [LG-GG-202401-ADAD060200]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202200479]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-LZX0033]; CQMU Program for Youth Innovation in Future Medicine [W0158]; University of Science and Technology of China

基金资助正文：We thank the National Key R&D Program of China 2021ZD0202402 (H.X.), the National Key R&D Program of China 2021YFA1101401 (Y.Z.), the National Natural Science Foundation of China grants 82071213 (Y.Z.), 82271472 (H. Zhang), 92049202, and 92149303 (H.X.), a start-up funding from Xiamen University (Y.Z.), the Lingang Laboratory (grant no. LG-GG-202401-ADAD060200), the Science and Technology Research Program of Chongqing Municipal Education Commission (KJQN202200479), the Natural Science Foundation of Chongqing (CSTB2022NSCQ-LZX0033), and CQMU Program for Youth Innovation in Future Medicine (W0158). We thank Qiang Liu from University of Science and Technology of China; Zhihan Wang at West China School of Basic Medical Sciences & Forensic Medicine at Sichuan University; and Luming Yao, Caiming Wu, Baoying Xie, Haiping Zheng, Jingru Huang, Qingfeng Liu, Xiang You, Zhenni Xu, Yaying Wu and Hao Sun at Core Facility of Biomedical Sciences at Xiamen University for providing technical support.r funding from Xiamen University (Y.Z.) , the Lingang Laboratory (grant no. LG-GG-202401-ADAD060200) , the Science and Technology Research Program of Chongqing Municipal Education Commission (KJQN202200479) , the Natural Science Foundation of Chongqing (CSTB2022NSCQ-LZX0033) , and CQMU Program for Youth Innovation in Future Medicine (W0158) . We thank Qiang Liu from University of Science and Technology of China; Zhihan Wang at West China School of Basic Medical Sciences & Forensic Medicine at Sichuan University; and Luming Yao, Caiming Wu, Baoying Xie, Haiping Zheng, Jingru Huang, Qingfeng Liu, Xiang You, Zhenni Xu, Yaying Wu and Hao Sun at Core Facility of Biomedical Sciences at Xiamen University for providing technical support.