Fagpressenytt

... In addition, their activation has been associated with chronic inflammation that may drive atherosclerosis, metabolic- and neurodegerative disease, cancer and autoimmunity. Currently we know of 5 types of receptor proteins that can form inflammasomes; NLRP1, NLRP3, NLRC4, AIM2, and Pyrin. They all detect intracellular pathogen associated molecular patterns (PAMPs) present on various microbes. One of the inflammasomes, NLRP3, can also respond to intracellular sterile activators associated with cellular damage (DAMPs). Most of our molecular understanding of inflammasome activation and function comes from studies of the NLRP3 receptor.

When an inflammasome receptor protein, such as NLRP3, detects a pathogen, inflammatory agent or cellular damage, it will result in receptor activation, oligomerization and recruitment of an adaptor protein called ASC. The ASC adaptor consists of a pyrin domain (PYD) and a caspase activation and recruitment domain (CARD). These domains are used for recruiting the inflammasome receptor to caspase1. Inflammasome activation results in ASC filament formation and procaspase-1 recruitment and activation. This can be visualized as formation of intracellular ASC specks in macrophages (Fig. 1). When ASC specks are formed, caspase-1 will process the pro-forms of Interleukin