NLR‐containing inflammasomes: Central mediators of host defense and inflammation

Effect and Disease Indicative Role of Inflammation in Neurodegenerative Pathology: A Mechanistic Crosstalk of Promise and Dilemma

“…These are expressed when Aβ oligomers and fibrils induces lysosomal damage via NACHT, LRR and PYD domainscontaining protein 3 (NALP3). The NLR proteins are also a key component of signaling platforms, which detects inflammation together with participation in caspase1 dependent activation of the pro-inflammatory cytokines (IL-1β and IL-18) [52]. Microglial cells act on the region around senile plaques, causes increased in size, rapid multiplication and motility [19].…”

Lessons from Genomic Profiling in AS

“…One, including NODs (NOD 1-5 and CIITA), detects pathogen-associated molecular patterns (PAMPs) existing in Gram-negative bacteria cell walls and elicit responses that are distinct from those of the TLRs. The other NLR subgroup involves a large family of molecular complexes known as the "inflammasomes", the NLRPs (NLRP1-14) and the IPAF subfamily, consisting of IPAF and NAIP (Fitzgerald, 2010;Schroder & Tschopp, 2010). The inflammasomes are macromolecular cytosolic complexes composed of several proteins, some of which are found in all inflammasomes (pro-caspase-1, Apoptosis-associated Speck-like Protein Containing a Caspase Recruitment Domain-ASC), and others which are present depending on the inflammasome type (cardinal, pro-caspase-5, domain with function to find-FIIND).…”

An additional piece in the puzzle of neutrophil‐derived IL‐1β: The NLRP3 inflammasome

“…In particular, it has been shown that while the expression of the IL-1β mRNA and precursor protein usually needs to be induced in a so-called "priming" step by NF-κB-activating pathways, for instance via cell stimulation by TLR, C-type lectin receptor (CLR), or RIG-I-like receptor (RLR) ligands, the processing of the 31-kDa inactive cytosolic pro IL-1β precursor into the bioactive 17-kDa IL-1β (known as the "licensing" or "activation" step), mostly depends on autocatalytic cleavage of the cysteine protease caspase-1. Such cleavage is triggered by several structures termed as inflammasomes [5,6], which consist of a group of related multiprotein cellular complexes, among which the best characterized include receptors of the NLR (nucleotidebinding domain (NOD) leucine-rich repeat-like receptor) family of proteins, namely NLRP1 (NACHT, LRR, and PYD domains containing protein 1), NLRP3 and NLRC4, and a receptor of the HIN family of proteins, namely AIM2 (absent in melanoma 2). All these inflammasomal complexes often include the adapter molecule ASC, which specifically binds and recruits caspase-1 [5,6].…”

“…Such cleavage is triggered by several structures termed as inflammasomes [5,6], which consist of a group of related multiprotein cellular complexes, among which the best characterized include receptors of the NLR (nucleotidebinding domain (NOD) leucine-rich repeat-like receptor) family of proteins, namely NLRP1 (NACHT, LRR, and PYD domains containing protein 1), NLRP3 and NLRC4, and a receptor of the HIN family of proteins, namely AIM2 (absent in melanoma 2). All these inflammasomal complexes often include the adapter molecule ASC, which specifically binds and recruits caspase-1 [5,6]. Formation of the NLRP1, NLRC4, and AIM2 inflammasomes is promoted by specific stimuli, for instance those originating from microbes, while activation of the NLPR3 inflammasome occurs in response to a number of chemically or physically different triggers.…”