CAS OpenIR
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 PublicationJOURNAL OF NEUROINFLAMMATION
Volume18Issue:1Pages:14
AbstractBackground 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.
KeywordAlzheimer's disease Tau pathology Neurofibrillary tangles Neuroinflammation Synapse loss Rutin
DOI10.1186/s12974-021-02182-3
Language英语
WOS KeywordNF-KAPPA-B ; OXIDATIVE STRESS ; PROTEIN ; PHOSPHORYLATION ; CYTOTOXICITY ; PROPAGATION ; OLIGOMERS
Funding ProjectNational Natural Science Foundation of China[81971610]
WOS Research AreaImmunology ; Neurosciences & Neurology
WOS SubjectImmunology ; Neurosciences
Funding OrganizationNational Natural Science Foundation of China
WOS IDWOS:000663025200002
PublisherBMC
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/49247
Collection中国科学院过程工程研究所
Corresponding AuthorYu, Xiao-lin; Liu, Rui-tian
Affiliation1.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
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.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Sun, Xiao-ying]'s Articles
[Li, Ling-jie]'s Articles
[Dong, Quan-Xiu]'s Articles
Baidu academic
Similar articles in Baidu academic
[Sun, Xiao-ying]'s Articles
[Li, Ling-jie]'s Articles
[Dong, Quan-Xiu]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Sun, Xiao-ying]'s Articles
[Li, Ling-jie]'s Articles
[Dong, Quan-Xiu]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.