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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

Insights

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.

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.
Keywords:
ActivationAggressionApoptosisCaspaseCell deathCre-LoxProteaseSNIPerSexual BehaviorVMHvlVentromedial Hypothalamus

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