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Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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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 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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Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
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The human inflammasomes.

Oonagh Paerewijck1, Mohamed Lamkanfi1

  • 1Laboratory of Medical Immunology, Department of Internal Medicine and Paediatrics, Ghent University, Ghent, B-9000, Belgium.

Molecular Aspects of Medicine
|June 13, 2022
PubMed
Summary
This summary is machine-generated.

Inflammasome research has advanced significantly, revealing human-specific activation mechanisms and roles in diseases. This progress fuels the development of targeted therapies for autoimmune, metabolic, and cancer conditions.

Keywords:
CaspaseCell deathHuman diseaseInflammasomeInflammationPyroptosis

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Area of Science:

  • Immunology
  • Molecular Biology
  • Pathology

Background:

  • Decades of inflammasome research primarily used rodent models.
  • Recent advances focus on human inflammasome biology and adaptive immune cell involvement.
  • Inflammasome research is expanding into clinical applications and therapeutic development.

Purpose of the Study:

  • To review recent findings in inflammasome research.
  • To emphasize human-specific inflammasome activation mechanisms.
  • To explore the role of inflammasomes in various diseases.

Main Methods:

  • Review of recent scientific literature.
  • Analysis of clinical trial data.
  • Discussion of translational research efforts.

Main Results:

  • Characterization of human-specific inflammasome activation pathways.
  • Identification of inflammasome involvement in adaptive immunity.
  • Emerging therapeutic strategies targeting inflammasomes.

Conclusions:

  • Human inflammasome biology is distinct and crucial for understanding disease.
  • Inflammasome-targeted therapies show therapeutic potential.
  • Further research is needed to translate findings into effective treatments.