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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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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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The nucleic acid-sensing inflammasomes.

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Inflammasomes are innate immune signaling complexes. Recent studies reveal filament formation is key for inflammasome assembly and function, offering new therapeutic targets.

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Area of Science:

  • Innate immunity
  • Molecular and cellular biology
  • Structural biology

Background:

  • Inflammasomes are protein complexes crucial for innate immunity, regulating inflammatory responses.
  • While AIM2 and IFI16 inflammasome activation mechanisms are understood, NLRP3 inflammasome activation remains unclear.
  • Recent advances highlight filament formation as a general mechanism for signaling platform assembly.

Purpose of the Study:

  • To review recent progress in understanding inflammasome assembly and activation mechanisms.
  • To discuss the significance of filament formation in inflammasome complex assembly.
  • To explore the therapeutic potential of targeting inflammasome filament formation.

Main Methods:

  • Structural and biophysical studies of inflammasome components.
  • Analysis of protein-ligand interactions and complex assembly.
  • Review of recent literature on inflammasome research.

Main Results:

  • Filament formation by ASC pyrin domain and IFI16-dsDNA complex demonstrates higher-order polymer assembly.
  • Extracellular function of NLRP3-ASC inflammasome identified.
  • Higher-order polymer formation is a general mechanism for innate immune signaling platforms.

Conclusions:

  • Filament formation is a critical mechanism for inflammasome assembly and signaling.
  • The extracellular role of NLRP3-ASC inflammasomes presents new therapeutic avenues.
  • Further research into inflammasome complexes will enhance understanding of innate immunity.