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

作者：Xiaoying Sun, Lingjie Li, Quan-xiu Dong, Jie Zhu, Yaru Huang, Shengjie Hou, Xiaolin Yu, Rui‐tian Liu · 发表于：Journal of Neuroinflammation · 年份：2021 · DOI：10.1186/s12974-021-02182-3 · 被引用次数：282 · 研究领域：Alzheimer's disease research and treatments、Medicinal Plants and Neuroprotection、Neurological Disease Mechanisms and Treatments

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-1β and TNF-α 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-1β and TNF-α, 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 olig...