The Microglial NLRP3 Inflammasome in Multiple Sclerosis: Bridging Innate Immunity, Chronic Inflammation, and IFN-β Response.
TL;DR
Dyelination and axonal degeneration in neuroinflammation are linked to the role of aberrant activity of the microglial NLRP3 inflammasome and it is suggested that an inhibition of inflammasome by IFN-β can be observed in a mechanistic interaction between NLRP3 signaling and response to treatment.
Abstract
Background: Multiple sclerosis (MS) is a chronic neurodegenerative and demyelinating disease that is marked by chronic inflammation of the central nervous system (CNS). Although interferon-β (IFN-β) remains one of the pillars of treatment for relapsing-remitting MS (RRMS), inconsistencies in the responses of patients signify the necessity to comprehend the immunopathological processes.Objectives: The NLRP3 (NOD-like receptor family pyrin domain-containing 3) inflammasome, an intracellular signaling platform controlling the activation of caspase-1 and the maturation of interleukin-1β (IL-1β) and interleukin-18 (IL-18) has been of considerable interest among emerging molecular actors. Microglia, the native CNS macrophage, are the center stage of tissue damage and repair.Results: Demyelination and axonal degeneration in neuroinflammation are linked to the role of aberrant activity of the microglial NLRP3 inflammasome. In addition, it is also suggested that an inhibition of inflammasome by IFN-β can be observed in a mechanistic interaction between NLRP3 signaling and response to treatment.Conclusion: In this literature review, the presented data summarize the existing information about the contribution of NLRP3 to the pathogenesis of MS disease, microglial activation, and IFN-β regulation, and how this pathway can be applied to shape personalized treatment approaches.