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Monitoring Cleaved Caspase-3 Activity and Apoptosis of Immortalized Oligodendroglial Cells using Live-cell Imaging and Cleaveable Fluorogenic-dye Substrates Following Potassium-induced Membrane Depolarization
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Caspases in Huntington's disease.

R O Sanchez Mejia1, R M Friedlander

  • 1Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry
|January 5, 2002
PubMed
Summary
This summary is machine-generated.

Caspase activation contributes to cell death in Huntington's disease (HD). Inhibiting caspases in HD mouse models delayed disease onset and prolonged survival, suggesting a potential therapeutic strategy for human patients.

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Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 2022

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by mutations in the huntingtin (htt) gene.
  • The precise function of huntingtin protein remains largely unknown.
  • Mutant htt has been linked to cellular dysfunction and death pathways.

Purpose of the Study:

  • To investigate the role of caspases in Huntington's disease pathogenesis.
  • To evaluate the therapeutic potential of caspase inhibition in HD.

Main Methods:

  • Utilized a transgenic mouse model of Huntington's disease.
  • Assessed transcriptional up-regulation and activation of caspase-1 and caspase-3.
  • Administered caspase inhibitors to HD-transgenic mice.

Main Results:

  • Demonstrated transcriptional up-regulation and activation of caspase-1 and caspase-3 in HD mouse models.
  • Observed caspase activation in human HD brains, confirming relevance.
  • Caspase inhibition in mice led to delayed symptom onset, slower progression, and increased survival.

Conclusions:

  • Caspase activation is implicated in the cellular dysfunction and death observed in Huntington's disease.
  • Caspase inhibition represents a promising therapeutic avenue for Huntington's disease that warrants clinical investigation.