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Chulalongkorn Medical Journal

Abstract

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a critical multiprotein complex of the innate immune system that functions as a molecular sensor for a wide array of danger signals. While its activation is essential for host defense and tissue homeostasis, its dysregulation is increasingly implicated in the pathophysiology of numerous inflammatory disorders. This review article synthesizes the current molecular understanding of the NLRP3 inflammasome, focusing on its dual role in health and disease. We first provide a concise overview of the canonical two-step mechanism of NLRP3 activation and the intricate molecular checkpoints including genetic factors, post-translational modifications, and organellar stress that govern its activity. Subsequently, we analyze the pathological consequences of both NLRP3 hyper-activation, which drives chronic inflammatory conditions such as metabolic and neurodegenerative diseases, and hypo-activation, which compromises host defense against pathogens and can impair anti-tumor immunity. With this foundational knowledge, we critically examine the emerging evidence linking NLRP3 inflammasome dysregulation to the sterile inflammation that characterizes devastating pregnancy complications, namely preeclampsia and implantation failure. We propose that an imbalance in NLRP3 activity disrupts the delicate immunological equilibrium required for a successful pregnancy. Finally, we survey the therapeutic landscape, discussing strategies from direct small-molecule inhibitors like MCC9

DOI

10.56808/2673-060X.5725

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