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NLRP3

HGNC:16400

Tuesday 28 February 2017

NALP3

WKP

Definition : NACH T, LRR and PYD domains-containing protein 3 (NALP3 ) also known by cryopyrin is a protein that in humans is encoded by the NLRP3 gene located on the long arm of chromosome 1.

NALP3 is expressed predominantly in macrophages and as a component of the inflammasome (" NLRP3 inflammasome " , detects products of damaged cells such as extracellular ATP and crystalline uric acid.

Activated NALP3 in turn triggers an immune response.

Pathology

- The NLRP3 inflammasome has a critical role in NASH and the progression of NAFLD to NASH.

- Mutations in the NLRP3 gene are associated with a number of organ specific autoimmune diseases.

- Mutations in the NLRP3 gene have been associated with a spectrum of dominantly inherited autoinflammatory diseases called cryopyrin-associated periodic syndrome (CAPS). This includes :

- Defects in this gene have also been linked to familial Mediterranean fever.

- The NALP3 inflammasome has a role in the pathogenesis of gout and neuroinflammation occurring in protein-misfolding diseases, such as Alzheimer’s, Parkinson’s, and prion diseases.

- Amelioration of mouse models of many diseases has been shown to occur by deletion of the NLRP3 inflammasome, including gout, type 2 diabetes, multiple sclerosis, Alzheimer’s disease, and atherosclerosis.

- The ketone β-Hydroxybutyrate has been shown to block NLRP3 activation, and thus may be of benefit for many of these diseases.

- Deregulation of NALP3 has been connected with carcinogenesis. For example, all the components of the NALP3 inflammasome are downregulated or completely lost in human hepatocellular carcinoma.

References

- A critical role for the NLRP3 inflammasome in NASH . Nature Reviews Gastroenterology & Hepatology (2017) doi : 10.1038/nrgastro.2017.21