Jo Dong-Gyu, Lee Joo-Yong, Hong Yeon-Mi, Song Sungmin, Mook-Jung Inhee, Koh Jae-Young, Jung Yong-Keun
Department of Life Science, Kwangju Institute of Science and Technology, Kwangju, Korea.
J Neurochem. 2004 Feb;88(3):604-11. 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 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.
钙调宁蛋白/ DREAM / KChIP3被鉴定为一种钙结合蛋白，它与早老素相互作用，作为转录抑制因子，并与A型钾通道结合。在本研究中，我们假设钙调宁蛋白可能参与阿尔茨海默病的神经退行性变，并检测了阿尔茨海默病中钙调宁蛋白的表达。在阿尔茨海默病患者大脑的皮质区域以及瑞典突变β-淀粉样前体蛋白转基因小鼠大脑的新皮质和海马体中，钙调宁蛋白水平升高。在活化的星形胶质细胞以及β-淀粉样蛋白（Aβ）和刚果红阳性斑块周围的神经元中也观察到钙调宁蛋白的诱导。将培养的皮质和海马神经元暴露于Aβ42（一种淀粉样β肽，其在大脑中的沉积是阿尔茨海默病的一个特征），可诱导钙调宁蛋白的蛋白质和mRNA表达以及细胞死亡。此外，阻断钙调宁蛋白的表达可保护神经元细胞免受Aβ毒性。这些发现表明，钙调宁蛋白的慢性上调可能是患阿尔茨海默病的一个危险因素，可能是通过促进钙调宁蛋白介导的神经退行性变。
