Induction of pro-apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease and cultured neurons after amyloid-β exposure
Induction of pro-apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease and cultured neurons after amyloid-β exposure
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DOI：
10.1046/j.1471-4159.2003.02159.x
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发表时间：
2004-02-01
影响因子：
4.7
通讯作者：
Jung, YK
中科院分区：
文献类型：
--
作者：
Jo, DG;Lee, JY;Jung, YK
Calsenilin/DREAM/KChIP 3被鉴定为与早老素相互作用的钙结合蛋白，作为转录抑制因子，并结合A型钾通道。在这项研究中，我们假设calsenilin可能参与阿尔茨海默病的神经变性，并检查calsenilin在阿尔茨海默病中的表达。在阿尔茨海默病患者大脑的皮质区域以及瑞典突变型β-淀粉样前体蛋白转基因小鼠大脑的新皮质和海马体中，钙沈淀素水平升高。在活化的星形胶质细胞以及β-淀粉样蛋白（Abeta）和刚果红阳性斑块周围的神经元中也观察到钙生素的诱导。将培养的皮质和海马神经元暴露于A β 42（一种淀粉样β肽，其在脑中的沉积是阿尔茨海默病的特征），诱导钙生素蛋白和mRNA表达以及细胞死亡。此外，阻断钙senilin表达保护神经元细胞免受Abeta毒性。这些研究结果表明，钙生素的慢性上调可能是发展阿尔茨海默病的危险因素，可能是通过促进钙生素介导的神经变性。
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.