What is familial Mediterranean fever?
Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder that causes recurrent fevers and painful inflammation of your abdomen, chest and joints.
What is Pyrin inflammasome?
The pyrin inflammasome has evolved as an innate immune sensor to detect bacterial toxin-induced Rho guanosine triphosphatase (Rho GTPase)-inactivation, a process that is similar to the “guard” mechanism in plants.
What activates NLRP3?
The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation.
How common is familial Mediterranean fever?
Frequency. Familial Mediterranean fever primarily affects populations originating in the Mediterranean region, particularly people of Armenian, Arab, Turkish, or Jewish ancestry. The disorder affects 1 in 200 to 1,000 people in these populations. It is less common in other populations.
How do you get FMF?
Causes. FMF is caused by a mutation in a gene called MEFV. Children who have it usually inherit copies of the faulty MEFV gene from both parents. Some can develop symptoms that are very similar to FMF even if they inherit only one copy of the faulty gene from one parent.
What is Pyrin structure?
Structure. Pyrin domains are a ~90 amino acid motif present only at the N-terminus of proteins. The core is made of highly conserved hydrophobic residues surrounded by five or six alpha helices with α1→2 linkages. The hydrophobic core allows self-oligomerization into punctate or speck filamentous formations.
What is NLRP3 gene?
The NLRP3 gene provides instructions for making a protein called cryopyrin. Cryopyrin is a member of a family of proteins called intracellular “NOD-like” receptor (NLR) proteins. Cryopyrin is found mainly in white blood cells and in cartilage-forming cells (chondrocytes).
Where is NLRP3 located?
NLR family pyrin domain containing 3 (NLRP3) (previously known as NACHT, LRR and PYD domains-containing protein 3 [NALP3] and cryopyrin), is a protein that in humans is encoded by the NLRP3 gene located on the long arm of chromosome 1. Chr.
Where are inflammasomes located?
Inflammasomes are expressed primarily by myeloid cells and are located within the cell. The macromolecular inflammasome structure can be visualized by cryo-electron microscopy. This complex has been found to play a role in a variety of disease models in mice and several have been genetically linked to human diseases.
How many different inflammasomes are there?
Four key inflammasomes, namely NLRP1, NLRP3, NLRC4, and AIM2, have been best characterized. Activation of these inflammasomes leads to the processing and secretion of inflammatory cytokines, including IL-1β and IL-18, as well as leading to an inflammatory form of cell death termed pyroptosis.