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Phoenixin-20 Ameliorates Lipopolysaccharide-Induced Activation of Microglial NLRP3 Inflammasome

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Abstract

Injury associated with neuroinflammation has been linked with several kinds of neurodegenerative diseases. The activation of the NLRP3 inflammasome plays an important role in microglia-mediated inflammation. Phoenixin (PNX)-20 is a newly discovered neuropeptide with pleiotropic effects involved in the regulation of reproductive and cognitive function, depression, and food uptake. This study investigated whether PNX-20 possesses a protective effect against lipopolysaccharide (LPS)-induced activation of the NLRP3 inflammasome in microglia. Firstly, our results show that the PNX-20 treatment significantly prevented LPS-induced expression of NADPH oxidase 4 (NOX-4) and the generation of reactive oxygen species (ROS). Secondly, PNX-20 mitigated LPS-induced upregulation of TxNIP, an upstream regulator of NLRP3 inflammasome activation. Thirdly, further evaluation of the major components of the NLRP3 inflammasome revealed that PNX-20 inhibited LPS-mediated upregulation of NLRP3, ASC, and cleaved caspase-1 (P10). Notably, based on our results, the inhibitory effect of PNX-20 on the NLRP3 inflammasome results in the inhibition of IL-1β and IL-18 secretions. Finally, we found that PNX-20 ameliorated the reduction in SIRT1 expression induced by LPS. When microglial SIRT1 was inhibited by nicotine, PNX-20 lost its suppressive effect on the expression of NLRP3, ASC, and caspase-1, as well as the secretion of IL-1β and IL-18. As a result of these findings, we draw the conclusion that the neuroprotective effect of PNX-20 is dependent on SIRT1. Collectively, the study shows that PNX-20 has a regulatory effect via modulation of neuroinflammation.

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Authors and Affiliations

  1. Department of Neurology, First Affiliated Hospital, Hunan University of Medicine, Huaihua, No.225, Yushi Road, Hecheng District, Huaihua City, 418000, Hunan Province, China

    **angliang Zeng, Yanchun Li, Sicong Ma, Yidan Tang & Hanwen Li

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  1. **angliang Zeng
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  2. Yanchun Li
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  3. Sicong Ma
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  4. Yidan Tang
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  5. Hanwen Li
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Correspondence to Yanchun Li.

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Zeng, X., Li, Y., Ma, S. et al. Phoenixin-20 Ameliorates Lipopolysaccharide-Induced Activation of Microglial NLRP3 Inflammasome. Neurotox Res 38, 785–792 (2020). https://doi.org/10.1007/s12640-020-00225-w

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  • DOI: https://doi.org/10.1007/s12640-020-00225-w

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