Amyloid-β activates NLRP3 inflammasomes by affecting microglial immunometabolism through the Syk-AMPK pathway.

ABSTRACT: Neuroinflammation is considered one of major factors in the pathogenesis of Alzheimer's disease (AD). In particular, inflammasome activation, including NLRP3 inflammasome in microglia, is regarded as fundamental for the pro-inflammatory response of immune cells. However, the precise molecular mechanism through which the NLRP3 inflammasome is associated with AD pathologies remains unclear. Here, we show that amyloid-β activates the NLRP3 inflammasome in microglia by activating Syk and inhibiting AMPK. Deactivated AMPK induces metabolic dysregulation, mitochondrial fragmentation, and reactive oxygen species formation, leading to the activation of the NLRP3 inflammasome. In addition, flufenamic acid (FA), a member of non-steroidal anti-inflammatory drugs, was found to effectively inhibit acti

SUBMITTER: Jung ES 

PROVIDER: S-EPMC9124305 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature