Figure 2.

Activation mechanism of nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) inflammasome. NLRP3 is activated by two signals when it senses the stimulation of aging or estrogen deficiency through toll like receptors (TLRs). The first priming process (Signal 1) is the expression of NLRP3 and inflammatory factors under the action of the NF-κB transcription factor. Next, it induces uniform downstream host-derived cellular events, including K⁺ efflux, Ca²⁺ efflux, reactive oxygen species (ROS) generation, and lysosomal damage. ASC is an adaptor molecule responsible for connecting NLRP3 and caspase-1 precursors, and then recruits the precursor caspase-1 into an activated form (Signal 2). Activated caspase-1 cleaves the precursors of IL-1β and IL-18 into mature forms and causing inflammation.