The Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that plays an important role in neuroinflammatory diseases, including Alzheimer's disease (AD). NLRP3 inflammasome activation involves upstream priming and activation signals, including amyloid-β aggregates, mitochondrial dysfunction, and oxidative stress, which promote inflammasome assembly and trigger downstream effector responses. This leads to caspase-1 activation and cleavage of GSDMD and the subsequent release of pro-inflammatory cytokines such as IL-1β and IL-18, thereby amplifying neuroinflammation and contributing to the neuronal damage characteristic of AD. Two known pathways of NLRP3 inflammasome activation are the canonical pathway, mediated by caspase-1, and the non-canonical pathway, mediated by caspase-11 (in mice) or caspase-4/5 (in humans). The use of phytochemicals to prevent NLRP3 inflammasome activation offers potential to reduce neuroinflammation and maintain neuronal integrity in AD. Phytochemicals such as resveratrol, ginkgolide B, and saffron, among others, have been shown to modulate the activity of the NLRP3 inflammasome through various mechanisms, including the inhibition of NLRP3 assembly, suppression of inflammasome priming signals, and regulation of downstream signaling pathways. Overall, phytochemicals that target NLRP3 inflammasome activation may offer potential benefits for AD management by attenuating neuroinflammation and protecting against neuronal damage.
