Induction of pro-apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease and cultured neurons after amyloid-beta exposure.
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 beta-amyloid precursor protein transgenic mice brains. Induction of calsenilin was also observed in the activated astroglia as well as in the neurons surrounding beta-amyloid (Abeta)- and Congo red-positive plaques. Exposing cultured cortical and hippocampal neurons to Abeta42, an amyloid-beta 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 Abeta 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.
Jo
Dong-Gyu
DG
Department of Life Science, Kwangju Institute of Science and Technology, Kwangju, Korea.
Lee
Joo-Yong
JY
Hong
Yeon-Mi
YM
Song
Sungmin
S
Mook-Jung
Inhee
I
Koh
Jae-Young
JY
Jung
Yong-Keun
YK
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D051605:Kv Channel-Interacting Proteins; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics
D016229:Amyloid beta-Peptides; D002135:Calcium-Binding Proteins; C496756:Csen protein, mouse; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; D010446:Peptide Fragments; D012097:Repressor Proteins; C075222:amyloid beta-protein (1-42)