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Caspases01:24

Caspases

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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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Apoptosis01:30

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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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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.
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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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Evaluation of Caspase Activation to Assess Innate Immune Cell Death
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Caspases in PANoptosis.

Kaiyuan Song1, Yongbin Wu1, Sipin Tan1

  • 1Department of Pathophysiology, Xiangya School of Basic Medicine Science, Central South University, Changsha, PR China; Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, PR China; National Medicine Functional Experimental Teaching Center, Central South University, Changsha, PR China.

Current Research in Translational Medicine
|February 22, 2025
PubMed
Summary
This summary is machine-generated.

Regulated cell death pathways like pyroptosis, apoptosis, and necroptosis extensively crosstalk. PANoptosis, a new inflammatory cell death pathway, integrates features of these pathways and involves caspases, offering new therapeutic targets.

Keywords:
PANoptosiscaspase-6caspase-8

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Area of Science:

  • Cellular Biology
  • Immunology
  • Molecular Biology

Background:

  • Three major regulated cell death (RCD) pathways—apoptosis, pyroptosis, and necroptosis—are known to interact.
  • PANoptosis is a recently identified RCD pathway that combines features of apoptosis, pyroptosis, and necroptosis.
  • Caspases, crucial cysteine proteases, are involved in apoptosis, pyroptosis, and necroptosis.

Purpose of the Study:

  • To review the molecular mechanisms and crosstalk of apoptosis, pyroptosis, and necroptosis.
  • To explore the discovery and disease associations of PANoptosis.
  • To discuss the role of caspases, particularly caspase-6 and caspase-8, in PANoptosis.

Main Methods:

  • Literature review of molecular mechanisms in RCD.
  • Analysis of crosstalk between pyroptosis, apoptosis, and necroptosis.
  • Review of studies on PANoptosis discovery, disease links, and caspase involvement.

Main Results:

  • Established RCD pathways exhibit significant crosstalk.
  • PANoptosis integrates characteristics of apoptosis, pyroptosis, and necroptosis, involving caspases.
  • Caspase-6 and caspase-8 are key molecules in PANoptosis.

Conclusions:

  • Understanding RCD crosstalk and PANoptosis is crucial for disease intervention.
  • Caspases play a central role in PANoptosis.
  • This review provides a foundation for targeting PANoptosis in diseases.