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 language | English (US) |
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Pages (from-to) | 62-66 |
Number of pages | 5 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 305 |
Issue number | 1 |
DOIs | |
State | Published - May 23 2003 |
Keywords
- Alzheimer's disease
- Aβ
- Calsenilin
- Cell death
- Presenilin
- γ-Secretase