Chemerin-9 is neuroprotective in APP/PS1 transgenic mice by inhibiting NLRP3 inflammasome and promoting microglial clearance of Aβ

作者：Jiawei Zhang, Yaxuan Zhang, Lan Liu, Mengyuan Zhang, Xiaojie Zhang, Jiangshan Deng, Fei Zhao, Qiang Li, Xue Zheng, Bing Fu, Yuwu Zhao, Xiuzhe Wang · 发表于：Journal of Neuroinflammation · 年份：2025 · DOI：10.1186/s12974-024-03325-y · 被引用次数：10 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Inflammasome and immune disorders、Inflammation biomarkers and pathways

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder worldwide, and microglia are thought to play a central role in neuroinflammatory events occurring in AD. Chemerin, an adipokine, has been implicated in inflammatory diseases and central nervous system disorders, yet its precise function on microglial response in AD remains unknown. METHODS: ) oligomers followed by treatment with chemerin-9 in vitro. ChemR23 inhibitor α-NETA was further used to investigate whether the effects of chemerin-9 were ChemR23-dependent. RESULTS: We found that the expression of chemerin and ChemR23 was increased in AD. Intriguingly, treatment with chemerin-9 significantly ameliorated Aβ deposition and cognitive impairment of the APP/PS1 mice, with decreased microglial proinflammatory activity and increased phagocytic activity. Similarly, chemerin-9-treated primary microglia showed increased phagocytic ability and decreased NLRP3 inflammasome activation. However, the ChemR23 inhibitor α-NETA abolished the neuroprotective microglial response of chemerin-9. CONCLUSIONS: Collectively, our data demonstrate that chemerin-9 ameliorates cognitive deficits in APP/PS1 transgenic mice by boosting a neuroprotective microglial phenotype.