Toll-like receptor 4–myeloid differentiation primary response 88–nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway (TLR4–MyD88–NF-κB signaling pathway)

The TLR4–MyD88–NF-κB signaling pathway is a central innate immune cascade triggered by pathogen-associated molecules such as lipopolysaccharide (LPS). Once TLR4 on the cell surface recognizes a pathogen, it recruits the adaptor protein MyD88, which in turn initiates a kinase cascade, culminating in the activation and nuclear translocation of NF-κB. NF-κB then promotes transcription of pro-inflammatory cytokines (including TNF-α, IL-1β, and IL-6), leading to inflammation, apoptosis, and further immune cell recruitment[1][2][3][4][5][6]. Dysregulation of this pathway is implicated in a wide range of diseases, including chronic inflammatory conditions, diabetes complications, organ fibrosis, and cancer[2][5][6]. Although therapeutic interventions often target individual component proteins such as TLR4, MyD88, or NF-κB, the pathway itself is not considered a discrete molecular drug target[6][7].

Other names

TLR4/NF-κB pathwayTLR4–MyD88 pathwayToll-like receptor 4 pathwayTLR4 signalingMyD88-dependent NF-κB pathway

Inhibition of TLR4 receptor activation; Blocking MyD88-mediated signal transduction; Preventing IκB degradation to inhibit NF-κB nuclear translocation; Suppression of downstream cytokine production (e.g., TNF-α, IL-6).