Fig.1

Neuroinflammation activation. TLRs are a family of membrane-bound receptors that recognize and bind to PAMPs. Upon binding to PAMPs, TLRs recruit adaptor molecules such as MyD88, that form a molecular complex called Myddosome. The complex activates a subsequent kinase cascade, which leads to the release of NF-κB from the cytoplasm and translocation to the nucleus, where it regulates the expression of genes involved in inflammation, such as IL-1β and TNF-α. NLRs are a group of cytosolic receptors and sense DAMPs and PAMPs that enter the cell. When they detect pathogens, NLRs undergo oligomerization and recruit ASC to assemble the NLRP3 or NLRC4 inflammasome. The filamentous ASC then attracts pro-caspase 1, which becomes activated and cleaves pro-IL-1β into mature cytokines. Additionally, in the context of AD, Amyloid aggregation and Tau hyperphosphorylation can facilitate the formation of NLRP3 inflammasome leading to microglial activation. The interaction between Aβ and microglia activation is involved in diverse molecular signaling such as the TREM2–TYROBP axis. AP, adaptor proteins; DAMPs, danger-associated molecular patterns; PAMPs, Pathogen-associated molecular patterns; TLRs, Toll-like receptors; TNF-α, Tumor necrosis factor-alpha; ASC, Apoptosis-associated speck-like protein containing a CARD; NLRP3, NOD-like receptor family pyrin domain containing 3; NLRPC4, NOD-like receptor family CARD domain-containing protein 4; AD, Alzheimer's disease; Aβ, amyloid beta; TREM2, triggering receptor expressed on myeloid cells 2; TYROBP, tyrosine kinase binding protein; GDMD: gasdermin D