NLRP3 inflammasome

The NLRP3 inflammasome is a protein complex that assembles inside immune cells in response to danger signals and activates the inflammatory cytokines IL-1 beta and IL-18.

NLRP3 is a sensor protein that stays inactive until it detects a broad set of triggers, including potassium leaking from the cell, crystals of uric acid or cholesterol, mitochondrial damage and some microbial products. Assembly requires two steps: a priming signal, usually through NF-kB, that raises NLRP3 levels, and then an activation signal that causes NLRP3 to cluster with an adaptor protein and the enzyme caspase-1. Caspase-1 cuts the inactive precursors of IL-1 beta and IL-18 into their active forms and can trigger a fiery form of cell death called pyroptosis.

Inherited mutations that keep NLRP3 switched on cause rare periodic fever syndromes, and excessive activation is implicated in gout, atherosclerosis, type 2 diabetes and neurodegenerative disease, where it is now a drug target. CBD has been examined in cell and animal models for effects on NLRP3-related signaling; the evidence is preclinical and no clinical conclusion follows.