β-Amyloid(1-40)-induced apoptosis of cultured cortical neurones involves calpain-mediated cleavage of poly-ADP-ribose polymerase

Barry Boland, Veronica Campbell

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

β-Amyloid(1-40)-induced apoptosis of cultured cortical neurones involves calpain-mediated cleavage of poly-ADP-ribose polymerase. β-Amyloid protein is thought to contribute to the pathophysiology of Alzheimer's disease by inducing neuronal apoptosis. Our previous work has demonstrated that β-amyloid activates voltage-dependent Ca2+ channels in the cortex, resulting in an increase in intracellular Ca2+ concentration. Calpain is a Ca2+-dependent neutral protease which becomes activated following alterations in intracellular Ca2+ homeostasis. In this study we have demonstrated that β-amyloid increases calpain activity in cultured cortical neurones in a time-dependent manner. Use of the cell-permeable calpain inhibitor, MDL 28170, has identified cleavage of the DNA-repair enzyme, poly-ADP-ribose polymerase, and DNA fragmentation as downstream consequences of calpain activation. Thus, we propose that the stimulatory effect of β-amyloid on Ca2+ influx triggers calpain-mediated DNA fragmentation in cultured cortical neurones.

Original languageEnglish
Pages (from-to)179-186
Number of pages8
JournalNeurobiology of Aging
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 2003
Externally publishedYes

Keywords

  • β-Amyloid
  • Apoptosis
  • Calpain
  • Poly-ADP-ribose polymerase

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