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The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
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The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
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Related Experiment Video

Updated: Jul 4, 2025

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1&#946; in Human Monocyte-derived Dendritic Cells
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Targeting NLRP3 Inflammasome: Structure, Function, and Inhibitors.

Shengying Lou1,2, Miaolian Wu2, Sunliang Cui1,3

  • 1Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Current Medicinal Chemistry
|February 4, 2024
PubMed
Summary

The NLRP3 inflammasome is key to innate immunity but its dysfunction causes diseases. This review covers NLRP3 inflammasome structure, function, and inhibitors, aiding drug development for inflammatory and other conditions.

Keywords:
NLRP3drug discoveryfunctioninflammasomeinhibitorprotein complexes.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Pharmacology

Background:

  • Inflammasomes are crucial protein complexes in innate immunity, detecting stimuli and danger signals.
  • The NLRP3 inflammasome plays a vital role in pathogen defense and maintaining cell homeostasis.
  • Dysregulation of NLRP3 inflammasome is linked to inflammatory diseases, cancer, and neurodegenerative conditions.

Purpose of the Study:

  • To summarize recent advancements in the structure, function, and inhibitors of the NLRP3 inflammasome.
  • To provide an overview of current therapeutic strategies targeting NLRP3.
  • To outline future directions for NLRP3-targeted drug discovery and development.

Main Methods:

  • Literature review of scientific publications on NLRP3 inflammasome.
  • Analysis of structural and functional data of NLRP3.
  • Compilation of information on existing and emerging NLRP3 inhibitors.

Main Results:

  • Detailed summary of NLRP3 inflammasome assembly, activation pathways, and downstream effects.
  • Identification of key molecular players and regulatory mechanisms.
  • Cataloging of diverse small-molecule and biologic inhibitors targeting NLRP3.

Conclusions:

  • NLRP3 inflammasome is a significant therapeutic target due to its role in numerous diseases.
  • A growing number of NLRP3 inhibitors show promise for treating inflammatory and other related pathologies.
  • Further research into NLRP3 inhibitors is essential for advancing drug development and clinical applications.