NALP3

NACHT, LRR and PYD domains-containing protein 3 (NALP3) or cryopyrin is a is_associated_with::protein that in humans is encoded by the NLRP3 (NOD-like receptor family, pyrin domain containing 3) is_associated_with::gene. The gene is also called cold induced autoinflammatory syndrome 1 (CIAS1) and is located on the long arm of is_associated_with::chromosome 1. Another name for the protein is caterpiller-like receptor 1.1 (CLR1.1).

This gene encodes a pyrin-like protein which contains a is_associated_with::pyrin domain, a nucleotide-binding site (NBS) domain, and a is_associated_with::leucine-rich repeat (LRR) motif. This protein interacts with pyrin domain (PYD) of apoptosis-associated speck-like protein containing a CARD (ASC). Proteins which contain the is_associated_with::caspase recruitment domain, CARD, have been shown to be involved in inflammation and immune response. This protein may function as an activator of is_associated_with::NF-κB signaling.

Mechanism
Crystalline structures activate the NLRP3 inflammasome in macrophages, leading to the production of IL-1β. Macrophage cell membrane binding to immobilized crystals induces IL-1β release, and this activation of the NLRP3 inflammasome is inhibited by blocking potassium efflux.

Pathology
The encoded protein may play a role in the regulation of is_associated_with::inflammation and is_associated_with::apoptosis. Mutations in this gene have been associated with a spectrum of dominantly inherited is_associated_with::autoinflammatory diseases called is_associated_with::cryopyrin-associated periodic syndrome (CAPS). This includes is_associated_with::familial cold autoinflammatory syndrome (FCAS), is_associated_with::Muckle-Wells syndrome (MWS), chronic infantile neurological cutaneous and articular (is_associated_with::CINCA) syndrome, and is_associated_with::neonatal-onset multisystem inflammatory disease (NOMID). Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene.

Cryopyrin is contained in the intracellular is_associated_with::inflammasome. It has also been linked to the is_associated_with::pathogenesis of is_associated_with::pseudogout, is_associated_with::gout, and is_associated_with::familial Mediterranean fever.

The is_associated_with::NLRP3 inflammasome has a role in the neuroinflammation occurring in is_associated_with::Alzheimer's disease.

Deregulation of NLRP3 has been connected with cancer pathogenesis. For example, one study showed that all of the NLRP3 components are downregulated or completely lost in human is_associated_with::hepatocellular carcinoma. Besides, there are evidences that NLRP3 is regulated by ROS, though the precise mechanisms of such regulation is largely elusive.