Inflammasome Signaling Pathway

Inflammasome, a complex of proteins, is an important part of the innate immune system. It has been identified that a variety of inflammasomes are involved in host defense responses against a variety of pathogens, and pathogens have evolved a variety of corresponding mechanisms to inhibit the activation of inflammasomes. Known inflammasomes generally contain apoptosis-associated microparticle protein (ASC) as an Adaptor, Caspase as an Effector, and a NOD-like receptor (NLR) family protein (such as NLRP1) or HIN200 family protein (such as AIM2) as a receptor protein. Consider the NLRP3 inflammasome, which consists of both initializing and activating signals: Signal1 initializes: it activates cytokines, pathway-associated molecular patterns (PAMPs) or host-derived danger signaling molecules (DAMPs), leading to the activation of TLRs and NF-κB and mediating the formation of NLRP3 inflammasome. Signal2 activates assembly: any number of DAMPs and PAMPs that activate upstream events. The functional NLRP3 inflammasome is formed by a variety of secondary signals such as potassium efflux, ROS production, lysosomal disruption, and mitochondrial stress. Inflammasome formation activates Caspase1, and activated Caspase-1 clears the precursors of IL-1β and IL-18 to produce the corresponding mature cytokines. Activated Caspase-1 can also cleave GSDMD, leading to a specific type of cell death called Pyroptosis. As an important component of innate immunity, NLRP3 inflammasome plays an important role in the body’s immune response and the occurrence of diseases. Activated by a variety of pathogens or danger signals, NLRP3 inflammasome plays a key role in a variety of diseases, including familial periodic autoinflammation, type 2 diabetes, Alzheimer’s disease, and atherosclerosis. Therefore, as the core of the inflammatory response, NLRP3 inflammasome may provide a new target for the treatment of various inflammatory diseases.