炎症体
粒体自噬
小胶质细胞
神经毒性
神经保护
神经炎症
上睑下垂
自噬
细胞生物学
神经退行性变
氧化应激
化学
吡喃结构域
半胱氨酸蛋白酶1
先天免疫系统
活性氧
炎症
药理学
线粒体ROS
生物
免疫学
细胞凋亡
医学
生物化学
免疫系统
毒性
有机化学
疾病
病理
作者
Xiaobin Han,Tong Xu,Qian Fang,Huajun Zhang,Lijun Yue,Gang Hu,Lingyun Sun
出处
期刊:Redox biology
[Elsevier]
日期:2021-08-01
卷期号:44: 102010-102010
被引量:181
标识
DOI:10.1016/j.redox.2021.102010
摘要
Activated microglia are an important type of innate immune cell in the brain, and they secrete inflammatory cytokines into the extracellular milieu, exert neurotoxicity to surrounding neurons and are involved in the pathogenesis of many brain disorders. Quercetin (Qu), a natural flavonoid, is known to have anti-inflammatory and antioxidant properties. Previous studies have shown that both increased reactive oxygen species (ROS) stress and decreased autophagy participate in the activation of microglial. In the current study, we showed that Qu significantly attenuated LPS-induced inflammatory factor production, cell proliferation and NF-κB activation of microglia. Importantly, Qu decreased the levels of NLR family, pyrin domain containing three (NLRP3) inflammasome and pyroptosis-related proteins, including NLRP3, active caspase-1, GSDMD N-terminus and cleaved IL-1β. Further study indicated that this anti-inflammatory effect of Qu was associated with mitophagy regulation. Importantly, Qu promoted mitophagy to enhance damaged mitochondrial elimination, which then reduced mtROS accumulation and alleviated NLRP3 inflammasome activation. Then, we confirmed that Qu treatment protected primary neurons against LPS-induced microglial toxicity and alleviated neurodegeneration in both depression and PD mouse models. Further IL-1β administration blunted these neuroprotective effects of Qu in vitro and in vivo. This work illustrated that Qu prevents neuronal injury via inhibition of mtROS-mediated NLRP3 inflammasome activation in microglia through promoting mitophagy, which provides a potential novel therapeutic strategy for neuroinflammation-related diseases.
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