Inflammasome biology, molecular pathology and therapeutic implications Awad, Fawaz Assrawi, Eman Louvrier, Camille Jumeau, Claire Georgin-Lavialle, Sophie Grateau, Gilles Amselem, Serge Giurgea, Irina Karabina, Sonia-Athina 2019-12-18T12:27:51Z 2019-12-18T12:27:51Z 2018-02-18
dc.description.abstract Inflammasomes are intracellular multiprotein signaling complexes, mainly present in myeloid cells. They commonly assemble around a cytoplasmic receptor of the nucleotide-binding leucine-rich repeat containing receptor (NLR) family, although other cytoplasmic receptors like pyrin have been shown to forminflammasomes. The nucleation of the multiprotein scaffolding platform occurs upon detection of a microbial, a danger or a homeostasis pattern by the receptor that will, most commonly, associate with the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) through homotypic domain interactions resulting in recruitment of procaspase-1. This will lead to the autoproteolytic activation of caspase-1, which regulates the secretion of proinflammatory IL1β and IL18 cytokines and pyroptosis, a caspase-1-mediated form of cell death. Pyroptosis occurs through cleavage of Gasdermin D, a membrane pore forming protein. Recently, non-canonical inflammasomes have been described, which directly sense intracellular pathogens through caspase-4 and -5 in humans, leading to pyroptosis. Inflammasomes are important in host defense; however, a deregulated activity is associated with a number of inflammatory, immune and metabolic disorders. Furthermore, mutations in inflammasome receptor coding genes are causal for an increasing number of rare autoinflammatory diseases. Biotherapies targeting the products of inflammasome activation aswell as molecules that directly or indirectly inhibit inflammasome nucleation and activation are promising therapeutic areas. This review discusses recent advances in inflammasome biology, the molecular pathology of several inflammasomes, and current therapeutic approaches in autoinflammatory diseases and in selected common multifactorial inflammasome-mediated disorders. en_US
dc.identifier.issn 0163-7258
dc.language.iso en en_US
dc.publisher Elsevier Inc. en_US
dc.subject Autoinflammation en_US
dc.subject Inflammasomes en_US
dc.subject Pyrin en_US
dc.subject Pyroptosis en_US
dc.subject Cytokines en_US
dc.title Inflammasome biology, molecular pathology and therapeutic implications en_US
dc.type Article en_US
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