Induction of pro-apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease and cultured neurons after amyloid-β exposure
Article first published online: 13 JAN 2004
Journal of Neurochemistry
Volume 88, Issue 3, pages 604–611, February 2004
How to Cite
Dong-Gyu, J., Joo-Yong, L., Yeon-Mi, H., Sungmin, S., Inhee, M.-J., Jae-Young, K. and Yong-Keun, J. (2004), Induction of pro-apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease and cultured neurons after amyloid-β exposure. Journal of Neurochemistry, 88: 604–611. doi: 10.1111/j.1471-4159.2004.02159.x
- Issue published online: 13 JAN 2004
- Article first published online: 13 JAN 2004
- Received April 11, 2003; revised manuscript received July 18, 2003; accepted September 26, 2003.
- Aβ toxicity;
- Alzheimer's disease;
- neuronal cell death;
Calsenilin/DREAM/KChIP3 was identified as a calcium-binding protein that interacts with presenilins, serves as a transcription repressor, and binds to the A-type potassium channel. In this study, we hypothesized that calsenilin might be involved in the neurodegeneration of Alzheimer's disease and examined calsenilin expression in Alzheimer's disease. Calsenilin levels were elevated in the cortex region of Alzheimer's patient brains and in the neocortex and the hippocampus of Swedish mutant β-amyloid precursor protein transgenic mice brains. Induction of calsenilin was also observed in the activated astroglia as well as in the neurons surrounding β-amyloid (Aβ)- and Congo red-positive plaques. Exposing cultured cortical and hippocampal neurons to Aβ42, an amyloid-β peptide whose deposition in the brain is a characteristic of Alzheimer's disease, induced both calsenilin protein and mRNA expression, and cell death. Moreover, blocking the calsenilin expression protected the neuronal cells from Aβ toxicity. These findings suggest that chronic up-regulation of calsenilin may be a risk factor for developing Alzheimer's disease, perhaps by facilitating calsenilin-mediated neurodegeneration.