Nucleotide-binding oligomerization domain-like receptor (NLR)

NOD-like receptor proteins are a highly conserved family of intracellular pattern recognition receptors, best known for their roles in the innate immune response. They detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) that enter cells, triggering oligomerization and initiating key inflammatory signaling cascades, such as activation of NF-κB, MAPKs, and formation of inflammasomes. Structurally, NLRs feature an N-terminal effector domain (CARD, PYD, BIR, or acidic), a NACHT nucleotide-binding domain, and leucine-rich repeats for ligand sensing. The family includes subgroups like NLRA (CIITA), NLRB (NAIP), NLRC (NOD1, NOD2, NLRC4), NLRP (NLRP1-14, involved in inflammasomes), and NLRX (NLRX1). Genetic variants in NLR genes are implicated in several inflammatory, autoimmune, and infectious diseases. NLRs are active in many cell types, notably immune cells and epithelial barriers. Therapies targeting the NLR pathway are under development for conditions driven by excessive inflammation. Key characteristics: - Intracellular PRRs critical for tissue homeostasis and inflammation - Scaffold formation for immune signaling - Diverse impact on human disease, particularly chronic inflammation and autoimmunity - Multi-domain structure facilitating selective responsiveness to molecular danger signals

Other names

Nucleotide-binding leucine-rich repeat receptorsNOD-like receptorNLR

Inhibition of oligomerization or inflammasome activation; Blocking secretion of proinflammatory cytokines (e.g., IL-1β); Downregulation of NF-κB signaling