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Related Concept Videos

Necrosis01:16

Necrosis

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Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
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Overview of Cell Death01:30

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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
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Apoptosis01:30

Apoptosis

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Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
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The Extrinsic Apoptotic Pathway01:17

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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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Autophagic Cell Death01:18

Autophagic Cell Death

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Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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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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Author Spotlight: THP-1 Macrophage Response to LPS/ATP &#8212; Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
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Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death.

Jianjin Shi1, Wenqing Gao1, Feng Shao1

  • 1National Institute of Biological Sciences, Number 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China.

Trends in Biochemical Sciences
|December 10, 2016
PubMed
Summary

Pyroptosis, a form of programmed necrosis, is now understood to be gasdermin-mediated, not just caspase-1 dependent. This cell death pathway involves gasdermin D and has broader implications for immunity and disease.

Keywords:
caspasegasdermininnate immunitynecrosispore-forming proteinpyroptosis

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Area of Science:

  • Cellular biology
  • Immunology
  • Molecular mechanisms of cell death

Background:

  • Pyroptosis was traditionally defined as caspase-1-mediated cell death in monocytes triggered by bacterial infections.
  • Inflammasomes activate caspase-1 in response to infectious and immunological stimuli.
  • Recent discoveries implicate caspase-11/4/5 in sensing intracellular lipopolysaccharide, broadening the scope of pyroptosis mediators and cell types involved.

Purpose of the Study:

  • To redefine pyroptosis based on recent findings.
  • To highlight the role of the gasdermin family in pyroptosis.
  • To explore the implications of gasdermin-mediated cell death in immunity and disease.

Main Methods:

  • Review of recent scientific literature.
  • Analysis of molecular pathways involved in pyroptosis.
  • Identification of key executioner molecules like gasdermin D.

Main Results:

  • Pyroptosis is redefined as gasdermin-mediated programmed necrosis.
  • Gasdermin D (GSDMD) is identified as a key executioner, targeted by both caspase-1 and caspase-11/4/5.
  • The gasdermin family, beyond GSDMD, is implicated in cell death, with largely unknown functions and activation mechanisms.

Conclusions:

  • Pyroptosis is a gasdermin-driven process, expanding beyond caspase-1.
  • The gasdermin family represents a novel area for investigating programmed necrosis in health and disease.
  • Further research into gasdermin functions is crucial for understanding immunity and genetic disorders.