Contribution of presenilin/γ-secretase to calsenilin-mediated apoptosis

Dong Gyu Jo, Jae Woong Chang, Hyun Seok Hong, Inhee Mook-Jung, Yong Keun Jung

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Mutant presenilins cause early-onset of familial Alzheimer's disease and render cells vulnerable to apoptosis. Calsenilin/DREAM/KChIP3 is a multifunctional calcium-binding protein that interacts with presenilin and mediates calcium-mediated apoptosis. In the present study, we report that the calsenilin-mediated apoptosis is regulated by presenilin. The expression of calsenilin was highly up-regulated in neuronal cells undergoing Aβ42-triggered cell death. The incidence of calsenilin-mediated apoptosis was diminished in presenilin-1-/- mouse embryonic fibroblast cells or neuronal cells stably expressing a loss-of-function presenilin-1 mutant. On the contrary, an array of familial Alzheimer's disease-associated presenilin mutants (gain-of-function) increased calsenilin-induced cell death. Moreover, γ-secretase inhibitors, including compound E and DAPT, decreased the calsenilin-induced cell death. These results suggest that the pro-apoptotic activity of calsenilin coordinates with presenilin/γ-secretase activity to play a crucial role in the neuronal death of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)62-66
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume305
Issue number1
DOIs
StatePublished - May 23 2003

Keywords

  • Alzheimer's disease
  • Calsenilin
  • Cell death
  • Presenilin
  • γ-Secretase

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