Redox Biology, Год журнала: 2021, Номер 44, С. 102010 - 102010
Опубликована: Май 25, 2021
Activated microglia are an important type of innate immune cell in the brain, and they secrete inflammatory cytokines into extracellular milieu, exert neurotoxicity to surrounding neurons involved pathogenesis many brain disorders. Quercetin (Qu), a natural flavonoid, is known have anti-inflammatory antioxidant properties. Previous studies shown that both increased reactive oxygen species (ROS) stress decreased autophagy participate activation microglial. In current study, we showed Qu significantly attenuated LPS-induced factor production, proliferation NF-κB microglia. Importantly, levels NLR family, pyrin domain containing three (NLRP3) inflammasome pyroptosis-related proteins, including NLRP3, active caspase-1, GSDMD N-terminus cleaved IL-1β. Further study indicated this effect was associated with mitophagy regulation. promoted enhance damaged mitochondrial elimination, which then reduced mtROS accumulation alleviated NLRP3 activation. Then, confirmed treatment protected primary against microglial toxicity neurodegeneration depression PD mouse models. IL-1β administration blunted these neuroprotective effects vitro vivo. This work illustrated prevents neuronal injury via inhibition mtROS-mediated through promoting mitophagy, provides potential novel therapeutic strategy for neuroinflammation-related diseases.
Язык: Английский