NLRP3
NLR family pyrin domain-containing 3
Also known as: NLRP3, NALP3, cryopyrin, CIAS1
Biology & Mechanism
NLRP3 is an innate immune sensor that forms the NLRP3 inflammasome complex, leading to caspase-1 activation and processing of pro-IL-1β and pro-IL-18. In microglia, NLRP3 is activated by diverse damage signals including amyloid-beta fibrils, tau aggregates, and alpha-synuclein. NLRP3 inflammasome activation in microglia is implicated in neuroinflammation driving neurodegeneration. NLRP3 inhibitors are in clinical development for multiple inflammatory diseases.
Open Questions
- —Does NLRP3 activation in microglia represent a cause or consequence of neurodegeneration?
- —Can CNS-penetrant NLRP3 inhibitors provide therapeutic benefit in AD or PD patients?
- —Are there genetic variants in the NLRP3 pathway associated with neurodegeneration risk?
Sources
- NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice (2015)
Last reviewed: June 1, 2026