SIRT1 decreases Aβ-induced IL-1β production by suppressing NLRP3 inflammasome activation and M1 microglial polarization

Abstract

Microglia polarize into the proinflammatory M1 phenotype drive Alzheimer’s disease (AD) pathogenesis through NLRP3 inflammasome-dependent maturation of interleukin (IL)-1β. Silent information regulator-1 (SIRT1) regulates a large number of cellular pathways and is related to aging and age-associated diseases, however, there were limited studies investigated whether SIRT1 can affect NLRP3 inflammasome and microglial activation and subsequent IL-1β production in AD. Here, we identified SIRT1 over-expression attenuated the release of IL-1β in amyloid-β (Aβ) treated microglia. Furthermore, our findings also revealed that NLRP3 inflammasome were less activated while the SIRT1 has been up-regulated. In addition, SIRT1 considerably alleviated the polarization of microglia toward to M1 phenotype mediated by Aβ, and the inhibitory on M1 polarization accompanied with the up-regulation of phosphorylated AMPK. This study demonstrated that SIRT1 can reduce IL-1β production by inhibiting the activation of NLRP3 and microglial phenotype toward M1, which suggesting SIRT1 may represent a potential strategy for modulating neuroinflammation in AD.