NLRP

NLRP proteins, NLRPs for short, together with the NOD1 and NOD2 proteins, are members of the NLR (Nod-like receptor) protein family and play a major role in innate immunity as pattern recognition receptors(PPRs) (Zambetti LP et al. 2012). Like the NOD proteins, NLRPs are exclusively expressed cytoplasmically. In humans, all NLRPs (they all contain the pyrin domain) are encoded by a common gene family.

NLRP proteins are characterized by their ability to form and activate the inflammasome, a multi-protein complex. Activation of the inflammasome leads to the expression of caspases, which in turn process and activate inactive interleukin-1beta and interleukin-18, thus initiating an inflammatory cascade.

To date, 14 members have been identified, NLRP1-NLRP14, whose functions cannot always be clearly evaluated. The effect of NLRP3, also known as cryopyrin, has been well researched. A number of ligands have been identified for this receptor protein. These include bacterial toxins, certain viruses and yeasts. Crystalline substances such as asbestos crystals and uric acid crystals can also activate the inflammasome via NLRP3. Mutations in the gene that codes for croypyrin(NLRP3 gene) lead to the disease family of familial cold urticaria or the related Muckle-Wells syndrome.

Overview of the NLRP genes and the proteins they encode (NLRPs):

• NLRP1 gene, a human gene encoding the NACHT, LRR and PYD domains-containing protein 1 (NLRP1 protein)
• NLRP2gene, a human gene that encodes NACHT, LRR and PYD domains-containing protein 2 (NLRP2 protein)
• NLRP3gene, a human gene that encodes the NACHT, LRR and PYD domains-containing protein 3 -NLRP3 protein (older name cryopyrin)(NLRP3 protein).
• NLRP4 gene, a human gene that encodes the protein of the same name. The NLRP4 protein may be involved in inflammation and the recognition of cytosolic pathogen-associated molecular patterns (PAMPs) that are not scavenged by membrane-bound receptors. It acts as a negative regulator of the type I interferon signaling pathway by serving as an adaptor to promote DTX4-mediated ubiquitination of activated TBK1 and its subsequent degradation. Furthermore, it suppresses NF-kappaB induction by the cytokines TNFA and IL1B, suggesting that it acts at a convergence point in these two cytokine signaling pathways.
• NLRP5 gene, a human gene encoding the NOD-like receptor family "Pyrin domain containing 5".
• NLRP6 gene, a human gene encoding the NOD-like receptor family "Pyrin domain containing 6".
• NLRP7 gene, a human gene encoding NACHT, LRR and PYD domains-containing protein 7.
• NLRP8 gene, a human gene encoding the NOD-like receptor family "Pyrin domain containing 8".
• NLRP9 gene, a human gene that encodes the NOD-like receptor family "Pyrin domain containing 9".
• NLRP10 gene, a human gene that encodes the NOD-like receptor family "Pyrin domain containing 10".
• NLRP11 gene, a human gene that encodes the NOD-like receptor family "Pyrin domain containing 11".

• NLRP12 gene, a human gene encoding the NOD-like receptor family "Pyrin domain containing 12". NLRP12-associated systemic autoinflammatory disease (NLRP12-AID) is a newly identified, rare autosomal dominant autoinflammatory systemic disease (SAID) that usually occurs in childhood and is caused by mutations in the NLRP12 gene. An NLRP12-AID variant is also known as familial cold autoinflammatory syndrome 2 (FCAS2). Clinically, the disease is characterized by periodic fever accompanied by inflammatory damage throughout the system. NLRP12-AID is diagnosed by early clinical identification and genetic detection.

  NLRP13 gene, a human gene encoding the NOD-like receptor family "Pyrin domain containing 13".

• NLRP14, a human gene encoding the NOD-like receptor family "Pyrin domain containing14".

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4. Sun RM et al. (2022) NLRP4 negatively regulates type I interferon response and influences the outcome in anti-programmed cell death protein (PD)-1/PD-ligand 1 therapy. Cancer Sci 113:838-851.
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