Fig. 5Figure 5
Molecular mechanism of NLRP3 inflammasome activation in Alzheimer’s disease (AD). The schematic depicts the two-step activation process: (1) Priming (Signal 1) via TLR/NF-κB signaling upregulates NLRP3 and pro-IL-1β; (2) Activation (Signal 2) occurs upon exposure to Aβ oligomers, ATP, ROS, lysosomal rupture, or mitochondrial dysfunction, leading to NLRP3 oligomerization, ASC speck formation, and caspase-1 activation. Active caspase-1 cleaves pro-IL-1β and pro-IL-18 into mature cytokines and processes gasdermin D (GSDMD) to form membrane pores, inducing pyroptosis. The downstream effects include glial activation, impaired Aβ clearance, tau hyperphosphorylation, and neuronal death, forming a self-amplifying neuroinflammatory loop central to AD pathogenesis