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Inflammasome activation is a key function mediated by the innate immune system in response to harmful stimuli, such as pathogens, dead cells or irritants. However, overt activation of inflammasomes may also lead to a variety of autoinflammatory and autoimmune diseases, including neurodegenerative diseases (such as multiple sclerosis, Alzheimer’s disease and Parkinson’s disease) and metabolic disorders (such as atherosclerosis, obesity and type II diabetes).<br>
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inflammasomes signaling pathway The innate immune system works as the first line of defense in protection from pathogens and host-derived signals of cellular distress. As an essential component of the innate immune response, inflammasomes can response to a wide range of physiological and pathogenic stimuli and play an important role in the clearance of pathogens or damaged cells. Inflammasomes are large multimeric complexes typically formed of a cytosolic pattern recognition receptor (specifically a nucleotide-binding domain and leucine-rich-repeat [NLR] or a melanoma 2 [AIM2]-like receptor [ALR] family member), and a bipartite adaptor protein (ASC), and an effector caspase pro-caspase-1. Assembly of inflammasome complexes is dependent on cytosolic sensing of pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) that gain access to the cytosol. Upon detecting specific stimuli, the activated receptor nucleates ASC which is an apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (CARD). Nucleated ASC sequentially recruits pro-caspase-1, which undergoes autocatalytic cleavage to produce the active subunits p10/p20 tetramer. Active caspase-1 can then proteolytically process cytokines pro-IL-1β and pro-IL-18, inducing the generation of the mature biologically active cytokines, as well as the initiation of an inflammatory form of cell death known as pyroptosis by autocatalysis and activation. Several distinct inflammasomes have been identified and the molecular composition of inflammasome complexes is stimulus dependent. The NLR family can be subdivided into NLRP or NLRC depending on whether the N terminus contains a pyrin or caspase activation and recruitment domain (CARD), respectively. NLR family members have been well established as NLRs capable of forming inflammasomes, such as NLRP1, NLRP3, and NLRC4. Among them, the NLRP3 inflammasome complex is the most characterized and can be activated in response to the widest array of stimuli. Find more: https://www.creative-diagnostics.com/inflammasome-signaling-pathway.htm
