title: The therapeutic potential of modifying inflammasomes and NOD-like receptors.
abstract: Inflammasomes are the central processing units (CPUs) responsible for decoding and integrating signals of foreignness, damage, danger, and distress released by pathogens, cells, and tissues. It was initially thought that the inflammasomes participated only in pathogen recognition and in the pathogenesis of a few, rare, hereditary inflammatory disorders. On the contrary, it is now clear that they have a central role in the pathogenesis of basically all types of chronic inflammation, in metabolic diseases and cancer. So far, six or possibly eight inflammasome subtypes have been identified. Their main, but by no means exclusive, function is to catalyze conversion of pro-IL-1β and pro-IL-18 into their respective mature forms. However, the different inflammasome subtypes may also participate in additional responses, e.g., proliferation, regulation of glycolytic metabolism, or cell activation, albeit it is not clear whether these effects are still mediated through IL-1β release or via modulation of other caspase-1-dependent or -independent pathways. Central to inflammasome organization and activity are proteins belonging to the nucleotide binding domain, leucine-rich repeat, or NOD-like receptor family. One relevant exception is the AIM2 inflammasome. NOD-like receptors belong to the superfamily of pattern recognition receptors, a group of highly conserved molecules specialized in the recognition of invariant molecular patterns diffused across species. Given their potent proinflammatory activity, it is anticipated that inflammasome activation is tightly controlled. In this review, I will summarize essential features of the known NOD-like receptors, the basic molecular structure of inflammasomes, their participation in pathophysiological responses, and their possible exploitation for therapy.
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of General Pathology, University of Ferrara, Via Borsari 46, 44121 Ferrara, Italy. fdv@unife.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Virgilio
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001343:Autophagy; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D063306:Mitophagy / Q000187:drug effects; D051192:Receptors, Pattern Recognition / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D058847:Inflammasomes; D018836:Inflammation Mediators; D051192:Receptors, Pattern Recognition