Role of cyclin-dependent kinase 5 in Alzheimer's brain.

细胞周期蛋白依赖性激酶 5 在阿尔茨海默病大脑中的作用。

• 批准号: 09044317
• 负责人: TOKUDA Masaaki
• 金额: $ 2.3万
• 依托单位: Kagawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09044317/
• 关键词: cyclin-dependent kinase; p35; phosphorylation; plasticity; Alzheimer's disease; neuronal degeneration; tau-protein; neurofilament; アルツハイマー脳; Cdk5

1. Expression levels and kinase activity of cychn-dependent kinase 5 (Cdk5) and its activator p35 were analyzed and compared using 8 Alzheimer's brains and 18 age-matched normal brains.2. Western blot analysis using specific antibodies for two proteins elucidated that Cdk5 and p35 increased by 20% and 15%, respectively, in Alzheimer's brains as compare with those in control brains.3. Cdk5/p35 activity in Alzheimer's brains was 20% higher than that in control brains. Especially, the activity in hippocampus in Alzheimer' s brains increased by 30%, however, that in forebrain did not increase significantly,4. Immunohistochemical study elucidated that distribution of both Cdk5 and p35 was dominantly observed at the regions of paired helical tangles which is characteristic in Alzheimer's brains.5. Southern blot analysis of Cdk5 and p35 showed no significant difference between Alzheimer's brains and control brains.6. Several proteins were assayed for the stimulatory or inhibitory activity of Cdk5/p35 activity, and S100A and B showed no stimulation or inhibition. Calbrain which we recently cloned showed a significant stimulation on the kinase activity.7. None of cAMP-dependent protein kinase, calcium/phospholipid-dependent protein kinase, calmodulin-dependent protein kinase 2 and casein kinase phosphorylated Cdk5/p35 and did not alter its activity.

1. 分析比较了8个阿尔茨海默病脑和18个年龄匹配的正常脑中cychn依赖性激酶5 （Cdk5）及其激活剂p35的表达水平和激酶活性。使用两种蛋白质特异性抗体的Western blot分析表明，与对照组相比，阿尔茨海默氏症大脑中的Cdk5和p35分别增加了20%和15%。老年痴呆症患者大脑中的Cdk5/p35活性比对照组高20%。特别是阿尔茨海默病患者大脑海马区活动增加了30%，而前脑区活动增加不明显。免疫组织化学研究表明，Cdk5和p35主要分布在阿尔茨海默病大脑特征的成对螺旋缠结区域。Cdk5和p35的Southern blot分析显示，阿尔茨海默病患者的大脑和对照组的大脑没有显著差异。检测了几种蛋白对Cdk5/p35活性的刺激或抑制作用，结果表明S100A和B对Cdk5/p35活性无刺激或抑制作用。我们最近克隆的Calbrain显示了对激酶活性的显著刺激。camp依赖性蛋白激酶、钙/磷脂依赖性蛋白激酶、钙调素依赖性蛋白激酶2和酪蛋白激酶均未使Cdk5/p35磷酸化，且未改变其活性。

项目成果

K.Hirooka et al.: "A novel calcium/calmodulin-dependent protein kinase IV like protein in rat retina." Vision Research. 37. 2029-2033 (1997)

K.Hirooka 等人：“大鼠视网膜中一种新型钙/钙调蛋白依赖性蛋白激酶 IV 样蛋白。”

T.Shishibori et al.: "Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family." Biochem.J.338. 583-589 (1999)

T.Shishibori 等人：“氨来呫、色甘酸和曲尼司特这三种不同的抗过敏药物可与 S100 蛋白家族的 S100A12 和 S100A13 结合。”

F.Yamaguchi et al.: "Molecular cloning of 5-hydroxytryptamine(5-HT)type 1 receptor genes from the Japanese puffer fish Fugu rubripes." Gene. 191. 219-223 (1997)

F.Yamaguchi 等人：“来自日本河豚红鳍河豚的 5-羟色胺 (5-HT) 1 型受体基因的分子克隆。”

T.Gotoh: "Activation of R-Ras by Ras-guanine nucleotide-releasing factor" Journal of Biological Chemistry. 272(30). 18602-18607 (1997)

T.Gotoh：“Ras-鸟嘌呤核苷酸释放因子激活 R-Ras”《生物化学杂志》。

T.Shishibori: "Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A 13 of the S100 protein family" Biochem.J.338. 583-589 (1999)

T.Shishibori：“三种不同的抗过敏药物，amlexanox、色甘酸和曲尼司特，与 S100 蛋白家族的 S100A12 和 S100A 13 结合”Biochem.J.338。