NLRP3 inflammasome signaling pathway (NLRP3/caspase-1 pathway)

The NLRP3/caspase‑1 signaling pathway, also known as the NLRP3 inflammasome signaling cascade, is a central component in innate immunity. Upon detection of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), cytosolic sensor protein NLRP3 oligomerizes and recruits adaptor protein ASC. This complex then recruits pro–caspase‑1 via CARD-CARD interactions. Activated caspase‑1 cleaves pro-inflammatory cytokines pro–IL‑1β and pro–IL‑18 into their active forms and processes gasdermin D to induce pyroptotic cell death. Dysregulation leads to chronic inflammation implicated in various diseases including autoimmunity, neurodegeneration, cardiovascular disorders, cancer, and metabolic syndromes. Therapeutic targeting focuses on inhibiting either upstream sensors like NLRP3 itself or downstream effectors such as caspase‐1.

Other names

NLRP3 inflammasome pathwayNLRP3-caspase-1 axisNOD-like receptor protein 3 inflammasome signalingInflammasome activation cascade

Drugs targeting this pathway typically act by one or more of the following mechanisms: - Direct inhibition of NLRP3 oligomerization/activation - Inhibition of caspase‑1 enzymatic activity - Blockade of ASC speck formation/adaptor function This results in reduced maturation/release of IL‑1β and IL‑18, dampening inflammation.