[en] Multiple sclerosis (MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system (CNS) mediated by autoreactive T cells directed against myelin antigens. Although the crucial role of adaptive immunity is well established in MS, the contribution of innate immunity has only recently been appreciated. Microglia are the main innate immune cells of the CNS. Similar to other myeloid cells, microglia recognize both exogenous and host-derived endogenous danger signals through pattern recognition receptors (PRRs) localized on their cell surface such as Toll Like receptor 4, or in the cytosol such as NLRP3. The second one is the sensor protein of the multi-molecular NLRP3 inflammasome complex in activated microglia that promotes the maturation and secretion of proinflammatory cytokines, interleukin-1β and interleukin-18. Overactivation of microglia and aberrant activation of the NLRP3 inflammasome have been implicated in the pathogenesis of MS. Indeed, experimental data, together with post-mortem and clinical studies have revealed an increased expression of NLRP3 inflammasome complex elements in microglia and other immune cells. In this review, we focus on microglial NLRP3 inflammasome activation in MS. First, we overview the basic knowledge about MS, microglia and the NLRP3 inflammasome. Then, we summarize studies about microglial NLRP3 inflammasome activation in MS and its animal models. We also highlight experimental therapeutic approaches that target different steps of NLRP inflammasome activation. Finally, we discuss future research avenues and new methods in this rapidly evolving area.
Precision for document type :
Review article
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Olcum, Melis; Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus Balcova, Izmir, Turkey
TASTAN, Bora ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuroinflammation Group ; Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus Balcova, Izmir, Turkey, Izmir International Biomedicine and Genome Institute (iBG-Izmir), Dokuz Eylul University Health Campus, Balcova, Izmir, Turkey
Kiser, Cagla; Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus Balcova, Izmir, Turkey, Izmir International Biomedicine and Genome Institute (iBG-Izmir), Dokuz Eylul University Health Campus, Balcova, Izmir, Turkey
Genc, Sermin; Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus Balcova, Izmir, Turkey, Izmir International Biomedicine and Genome Institute (iBG-Izmir), Dokuz Eylul University Health Campus, Balcova, Izmir, Turkey, Department of Neuroscience, Institute of Health and Science, Dokuz Eylul University Health Campus, Balcova, Izmir, Turkey
Genc, Kursad; Department of Neuroscience, Institute of Health and Science, Dokuz Eylul University Health Campus, Balcova, Izmir, Turkey
External co-authors :
yes
Language :
English
Title :
Microglial NLRP3 inflammasome activation in multiple sclerosis.
Publication date :
2020
Journal title :
Advances in Protein Chemistry and Structural Biology
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