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| Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer's disease | |
| Sun, Xiao-ying1,3; Li, Ling-jie1,3; Dong, Quan-Xiu1,3; Zhu, Jie1,2; Huang, Ya-ru1,3; Hou, Sheng-jie1,3; Yu, Xiao-lin1,2; Liu, Rui-tian1,2 | |
| 2021-06-11 | |
| Source Publication | JOURNAL OF NEUROINFLAMMATION
 |
| Volume | 18Issue:1Pages:14 |
| Abstract | Background Tau pathology is a hallmark of Alzheimer's disease (AD) and other tauopathies. During disease progression, abnormally phosphorylated forms of tau aggregate and accumulate into neurofibrillary tangles, leading to synapse loss, neuroinflammation, and neurodegeneration. Thus, targeting of tau pathology is expected to be a promising strategy for AD treatment. Methods The effect of rutin on tau aggregation was detected by thioflavin T fluorescence and transmission electron microscope imaging. The effect of rutin on tau oligomer-induced cytotoxicity was assessed by MTT assay. The effect of rutin on tau oligomer-mediated the production of IL-1 beta and TNF-alpha in vitro was measured by ELISA. The uptake of extracellular tau by microglia was determined by immunocytochemistry. Six-month-old male Tau-P301S mice were treated with rutin or vehicle by oral administration daily for 30 days. The cognitive performance was determined using the Morris water maze test, Y-maze test, and novel object recognition test. The levels of pathological tau, gliosis, NF-kB activation, proinflammatory cytokines such as IL-1 beta and TNF-alpha, and synaptic proteins including synaptophysin and PSD95 in the brains of the mice were evaluated by immunolabeling, immunoblotting, or ELISA. Results We showed that rutin, a natural flavonoid glycoside, inhibited tau aggregation and tau oligomer-induced cytotoxicity, lowered the production of proinflammatory cytokines, protected neuronal morphology from toxic tau oligomers, and promoted microglial uptake of extracellular tau oligomers in vitro. When applied to Tau-P301S mouse model of tauopathy, rutin reduced pathological tau levels, regulated tau hyperphosphorylation by increasing PP2A level, suppressed gliosis and neuroinflammation by downregulating NF-kB pathway, prevented microglial synapse engulfment, and rescued synapse loss in mouse brains, resulting in a significant improvement of cognition. Conclusion In combination with the previously reported therapeutic effects of rutin on A beta pathology, rutin is a promising drug candidate for AD treatment based its combinatorial targeting of tau and A beta. |
| Keyword | Alzheimer's disease Tau pathology Neurofibrillary tangles Neuroinflammation Synapse loss Rutin |
| DOI | 10.1186/s12974-021-02182-3 |
| Language | 英语 |
| WOS Keyword | NF-KAPPA-B ; OXIDATIVE STRESS ; PROTEIN ; PHOSPHORYLATION ; CYTOTOXICITY ; PROPAGATION ; OLIGOMERS |
| Funding Project | National Natural Science Foundation of China[81971610] |
| WOS Research Area | Immunology ; Neurosciences & Neurology |
| WOS Subject | Immunology ; Neurosciences |
| Funding Organization | National Natural Science Foundation of China |
| WOS ID | WOS:000663025200002 |
| Publisher | BMC |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ipe.ac.cn/handle/122111/49247 |
| Collection | 中国科学院过程工程研究所 |
| Corresponding Author | Yu, Xiao-lin; Liu, Rui-tian |
| Affiliation | 1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Innovat Acad Green Manufacture, Beijing 100190, Peoples R China 3.Univ Chinese Acad Sci, Sch Chem & Chem Engn, Beijing 100049, Peoples R China |
| First Author Affilication | Center of lonic Liquids and Green Engineering |
| Corresponding Author Affilication | Center of lonic Liquids and Green Engineering |
| Recommended Citation GB/T 7714 | Sun, Xiao-ying,Li, Ling-jie,Dong, Quan-Xiu,et al. Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer's disease[J]. JOURNAL OF NEUROINFLAMMATION,2021,18(1):14. |
| APA | Sun, Xiao-ying.,Li, Ling-jie.,Dong, Quan-Xiu.,Zhu, Jie.,Huang, Ya-ru.,...&Liu, Rui-tian.(2021).Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer's disease.JOURNAL OF NEUROINFLAMMATION,18(1),14. |
| MLA | Sun, Xiao-ying,et al."Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer's disease".JOURNAL OF NEUROINFLAMMATION 18.1(2021):14. |
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