Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer's disease

doi:10.1186/s12974-021-02182-3

	Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer's disease
	Sun, Xiao-ying 1,2; Li, Ling-jie 1,2; Dong, Quan-Xiu 1,2; Zhu, Jie 1,3; Huang, Ya-ru 1,2; Hou, Sheng-jie 1,2; Yu, Xiao-lin 1,3; Liu, Rui-tian 1,3
刊名	JOURNAL OF NEUROINFLAMMATION
	2021-06-11
卷号	18 期号:1 页码:14
关键词	Alzheimer's disease Tau pathology Neurofibrillary tangles Neuroinflammation Synapse loss Rutin
DOI	10.1186/s12974-021-02182-3
英文摘要	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.
资助项目	National Natural Science Foundation of China[81971610]
WOS关键词	NF-KAPPA-B ; OXIDATIVE STRESS ; PROTEIN ; PHOSPHORYLATION ; CYTOTOXICITY ; PROPAGATION ; OLIGOMERS
WOS研究方向	Immunology ; Neurosciences & Neurology
语种	英语
出版者	BMC
WOS记录号	WOS:000663025200002
资助机构	National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/49246]
专题	中国科学院过程工程研究所
通讯作者	Yu, Xiao-lin; Liu, Rui-tian
作者单位	1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Sch Chem & Chem Engn, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Innovat Acad Green Manufacture, Beijing 100190, Peoples R China
推荐引用方式 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.