Figure 1.

The activation of Toll-like receptors by ligands such as LPS or Aβ species can trigger the first signal for assembly of the NLRP3 inflammasome through nuclear factor kappa B (NF-kB). The second signal can be triggered after Aβ-mediated phagocytosis by TREM2. The Aβ overload causes lysosome disruption, releasing cathepsin B, which induces the signal for assembly of NLRP3. The inflammasome contains caspase-1 that cleaves pro-IL-1β and pro-IL-18, generating the mature forms of these inflammatory cytokines. IL-1β and IL-18, in turn, activate neutrophils, macrophages, and other microglial cells, amplifying the inflammatory response.