Nucleotide-binding oligomerization domain-like receptor signaling pathway (NLR signaling pathway)

The nucleotide-binding oligomerization domain-like receptor signaling pathway is a central innate immune cascade regulated by NOD-like receptors (NLRs), a family of cytosolic pattern recognition receptors that sense intracellular pathogens and cellular stress signals. Upon recognizing danger-associated or pathogen-associated molecular patterns, NLRs oligomerize, form multi-protein complexes (such as inflammasomes), and trigger intracellular signaling via NF-κB, MAPK, and caspase-1 pathways. This leads to the production and secretion of pro-inflammatory cytokines (notably IL-1β and IL-18), generation of anti-microbial peptides, initiation of autophagy, and regulation of apoptosis. Dysregulation of this pathway is implicated in a wide range of inflammatory, autoimmune, infectious, metabolic, and degenerative diseases. Therapeutic approaches chiefly focus on modulation of downstream effectors or specific NLR family members, rather than the pathway as a whole.

Other names

NLR signaling pathwayNOD-like receptor pathwayNLR pathwayNLRP signaling pathway (for inflammasome-related subtypes)

Inhibition of downstream cytokine signaling (e.g., blocking IL-1β, IL-18); Inhibition of inflammasome formation; Modulation of NF-κB or MAPK signaling; Agonism/antagonism at specific NLRs (NOD1, NOD2, NLRP3)