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Detecting Anastasis In Vivo by CaspaseTracker Biosensor
20:16

Detecting Anastasis In Vivo by CaspaseTracker Biosensor

Published on: February 1, 2018

A caspase cascade regulating developmental axon degeneration

David J Simon1, Robby M Weimer, Todd McLaughlin

  • 1Laboratory of Brain Development and Repair, Rockefeller University, New York, New York 10065, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|December 11, 2012
PubMed

Insights

Caspase-3 activation is critical for sensory axon degeneration, a process previously overlooked. This study reveals a pathway involving Caspase-9, Caspase-3, and Caspase-6, impacting both developmental and withdrawal-induced axon loss.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Axon degeneration shares similarities with programmed cell death.
  • Previous studies questioned the role of Caspase-3 in axon degeneration.
  • Caspase-6 was recently suggested to play a role.

Purpose of the Study:

  • To investigate the role of Caspase-3 and Caspase-6 in axon degeneration.
  • To elucidate the biochemical cascade leading to axon degeneration.
  • To understand the involvement of caspases in developmental axon pruning.

Main Methods:

  • Genetic deletion of Caspase-3 and Caspase-6 in vitro and in vivo.
  • Biochemical assays to determine caspase activation pathways.
  • Analysis of developmental axon pruning in knockout mice.

Main Results:

  • Genetic deletion of Caspase-6 offered partial protection against degeneration.
  • Caspase-6 activation was dependent on Caspase-3.
  • Genetic deletion of Caspase-3 fully protected against trophic factor withdrawal-induced degeneration.
  • A cascade from Bcl2 family regulators to Caspase-9, Caspase-3, and Caspase-6 was identified.
  • Caspase-3 and Caspase-6 knockout mice exhibited delayed developmental axon pruning.

Conclusions:

  • Caspase-3 plays a critical, previously underestimated role in sensory axon degeneration.
  • A specific caspase cascade (Caspase-9 -> Caspase-3 -> Caspase-6) drives degeneration.
  • Both Caspase-3 and Caspase-6 are implicated in normal developmental axon pruning.

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