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Alzheimer's Amyloid-beta Accelerates Human Neuronal Cell Senescence Which Could Be Rescued by Sirtuin-1 and Aspirin | |
2022-06-17 | |
发表期刊 | FRONTIERS IN CELLULAR NEUROSCIENCE (IF:4.2[JCR-2023],5.1[5-Year]) |
EISSN | 1662-5102 |
卷号 | 16 |
发表状态 | 已发表 |
DOI | 10.3389/fncel.2022.906270 |
摘要 | Cellular senescence is a major biological process related to aging. Neuronal cell senescence contributes to the pathogenesis of many aging-related neurodegenerative diseases including Alzheimer's disease (AD). In this study, we showed that amyloid-beta(42) oligomers (A beta), one of the core pathological players of AD, significantly upregulated the expression of senescence markers, p21, plasminogen activator inhibitor-1 (PAI-1), and SA-beta-gal (senescence-associated beta-galactosidase) in multiple human neuronal cells, including SK-N-SH cells, SH-SY5Y cells, and neural stem cell (NSC)-derived neuronal cells. Moreover, it was consistently observed among the cells that A beta promoted senescence-associated DNA damage as the levels of 8-OHdG staining, histone variant H2AX phosphorylation (gamma-H2AX), and genomic DNA lesion increased. Mechanism study revealed that the exposure of A beta markedly suppressed the expression of sirtuin-1 (SIRT1), a critical regulator of aging, and the exogenous expression of SIRT1 alleviated A beta-induced cell senescence phenotypes. To our surprise, a widely used cardiovascular drug aspirin considerably rescued A beta-induced cellular senescence at least partially through its regulation of SIRT1. In conclusion, our findings clearly demonstrate that exposure of A beta alone is sufficient to accelerate the senescence of human neuronal cells through the downregulation of SIRT1. |
关键词 | A beta cell senescence human neuronal cells SIRT1 DNA damage |
URL | 查看原文 |
收录类别 | SCI ; SCIE |
语种 | 英语 |
资助项目 | National Key Research and Development Program of China[2018YFA0108003] ; "Strategic Priority Research Program" of the Chinese Academy of Sciences[XDA16010309] ; National Science Foundation for Young Scientists of China[81901094] |
WOS研究方向 | Neurosciences & Neurology |
WOS类目 | Neurosciences |
WOS记录号 | WOS:000885442500001 |
出版者 | FRONTIERS MEDIA SA |
引用统计 | 正在获取...
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文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/251690 |
专题 | 生命科学与技术学院_特聘教授组_裴钢组 生命科学与技术学院_博士生 |
通讯作者 | Huang, Shichao; Pei, Gang |
作者单位 | 1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 2.Chinese Acad Sci, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,Univ Chinese Ac, Shanghai, Peoples R China 3.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Inst Regenerat Med, Shanghai East Hosp,Sch Life Sci & Technol, Shanghai, Peoples R China 4.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Sch Life Sci & Technol, Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China 5.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China |
第一作者单位 | 生命科学与技术学院 |
通讯作者单位 | 生命科学与技术学院 |
第一作者的第一单位 | 生命科学与技术学院 |
推荐引用方式 GB/T 7714 | Li, Yi,Lu, Juan,Hou, Yujun,et al. Alzheimer's Amyloid-beta Accelerates Human Neuronal Cell Senescence Which Could Be Rescued by Sirtuin-1 and Aspirin[J]. FRONTIERS IN CELLULAR NEUROSCIENCE,2022,16. |
APA | Li, Yi,Lu, Juan,Hou, Yujun,Huang, Shichao,&Pei, Gang.(2022).Alzheimer's Amyloid-beta Accelerates Human Neuronal Cell Senescence Which Could Be Rescued by Sirtuin-1 and Aspirin.FRONTIERS IN CELLULAR NEUROSCIENCE,16. |
MLA | Li, Yi,et al."Alzheimer's Amyloid-beta Accelerates Human Neuronal Cell Senescence Which Could Be Rescued by Sirtuin-1 and Aspirin".FRONTIERS IN CELLULAR NEUROSCIENCE 16(2022). |
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