NOD-like receptor signaling pathway (NLR signaling pathway)

The NOD-like receptor signaling pathway comprises intracellular proteins known as NOD-like receptors (NLRs), which act as sensors for pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) within the cytosol. These receptors are structurally defined by a central nucleotide-binding domain, leucine-rich repeats for ligand recognition, and variable N-terminal effector domains. Upon activation by microbial or stress signals, NLRs oligomerize and recruit various adaptor proteins, forming complexes such as inflammasomes (notably NLRP3), and activate downstream immune signaling cascades (NF-κB, MAPKs, IRFs). This leads to the production of pro-inflammatory cytokines, regulation of autophagy, and orchestration of innate and, indirectly, adaptive immune responses. NLR pathway dysregulation is implicated in numerous human diseases including chronic inflammation, autoimmunity, cancer, and infection susceptibility. Therapeutic investigation is ongoing, focusing on selective modulation of specific NLRs in disease contexts (with NLRP3 as a particularly prominent target).

Other names

NOD-like receptor (NLR) pathwayNucleotide-binding oligomerization domain-like receptor pathwayNLR signaling pathwayNOD signaling pathway (less common)Nodosome pathway (for specific complexes)

Inhibition or activation of NLRs to modulate inflammasome assembly; Blockade of cytokine release (e.g., IL-1β, IL-18); Modulation of downstream signaling (NF-κB, MAPK); Targeting upstream PAMP/DAMP recognition