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Related Concept Videos

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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The Intrinsic Apoptotic Pathway01:31

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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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CRISPR/Cas9 Genome Editing01:28

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The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...
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CRISPR01:59

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Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
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The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

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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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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
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Turning on caspases with genetics and small molecules.

Charles W Morgan1, Olivier Julien2, Elizabeth K Unger3

  • 1Department of Pharmaceutical Chemistry, University of California, San Francisco, California, USA; Graduate Group in Chemistry and Chemical Biology, University of California, San Francisco, California, USA.

Methods in Enzymology
|June 30, 2014
PubMed
Summary

Researchers explore activating specific caspases (aspartate-specific cysteine proteases) using genetic or small-molecule methods. This approach aims to understand cellular processes like apoptosis and inflammation, and develop new disease models and therapies.

Keywords:
ActivationAggressionApoptosisCaspaseCell deathCre-LoxProteaseSNIPerSexual BehaviorVMHvlVentromedial Hypothalamus

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Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Neuroscience

Background:

  • Caspases are crucial aspartate-specific cysteine proteases involved in apoptosis, differentiation, neuronal remodeling, and inflammation.
  • Understanding the specific roles of individual caspases in human cells remains a challenge.
  • Controlling caspase activity offers potential for biological insights and therapeutic strategies.

Purpose of the Study:

  • To provide a practical guide for activating specific caspases using genetic or small-molecule approaches.
  • To demonstrate the utility of controlled caspase activation in cellular and animal models.
  • To explore targeted neuronal function modulation via caspase activation.

Main Methods:

  • Utilizing genetic tools for caspase activation.
  • Employing small molecules to control caspase activity.
  • Implementing genetically controlled activation of an executioner caspase in the adult mammalian brain.

Main Results:

  • Demonstrated methods for activating specific caspases in cells and animals.
  • Showcased genetically controlled activation of an executioner caspase.
  • Successfully targeted the function of a defined group of neurons in the adult mammalian brain.

Conclusions:

  • Experimental control of caspase activity provides novel insights into fundamental biological processes.
  • Targeted caspase activation can enable new disease models and suggest therapeutic interventions.
  • Localized, genetic, and small-molecule-controlled caspase activation holds promise for precise cellular targeting.