Induction of pro‐apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease and cultured neurons after amyloid‐β exposure

• Published in: Journal of neurochemistry Vol. 88; no. 3; pp. 604 - 611
• Main Authors: Dong‐Gyu, Jo, Joo‐Yong, Lee, Yeon‐Mi, Hong, Sungmin, Song, Inhee, Mook‐Jung, Jae‐Young, Koh, Yong‐Keun, Jung
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.02.2004; Blackwell
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - pharmacology; Animals; apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Aβ toxicity; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Calcium-Binding Proteins - biosynthesis; Calcium-Binding Proteins - genetics; calsenilin; Cells, Cultured; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Humans; Kv Channel-Interacting Proteins; Male; Medical sciences; Mice; Mice, Transgenic; Middle Aged; Neurology; neuronal cell death; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Peptide Fragments - pharmacology; presenilin; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; Human; Cerebral cortex; Calcium; Alzheimer disease; Toxicity; Central nervous system; Presenilin; Amyloid precursor protein; Encephalon; Binding protein; neuronal cell death; Neuron; Cell death; β Amyloid protein; A-type potassium channel; Calsenilin; Alzheimer's disease; Aβ toxicity; Hippocampus; Apoptosis
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2004.02159.x

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.