Toll-like receptor 4 MyD88-dependent pathway (TLR4 MyD88-dependent pathway)

The Toll-like receptor 4 MyD88-dependent pathway is a canonical signaling cascade activated upon recognition of microbial components such as lipopolysaccharide (LPS) by Toll-like receptor 4 (TLR4) on immune and other cells. Engagement of TLR4 leads to recruitment of the adaptor protein MyD88 through the TIR (Toll/interleukin-1 receptor) domain. MyD88 then assembles with IRAK kinases to form the active “Myddosome,” resulting in downstream phosphorylation events and activation of transcription factors NF-κB and AP-1. This signaling pathway drives production of pro-inflammatory cytokines and is central to innate immune responses, but is also implicated in chronic inflammation, infection susceptibility, and diseases such as sepsis and autoimmune disorders

Other names

TLR4-MyD88 pathwayToll-like receptor 4 signaling (MyD88-dependent)TLR4 signaling pathway (canonical/MyD88)Canonical TLR4 pathway (MyD88-dependent)

Antagonism or inhibition of TLR4 to block signal initiation Inhibition of MyD88 recruitment or function to prevent downstream signaling Inhibition of IRAK kinases, TRAF6, or other downstream effectors to block signal propagation