Non-biased expression analysis to search for molecules associated with amyloid-beta induced hyperphosphorylation of tau

无偏表达分析，寻找与 β 淀粉样蛋白诱导的 tau 过度磷酸化相关的分子

• 批准号: 23591234
• 负责人: IKEUCHI Takeshi
• 金额: $ 3.24万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591234/
• 关键词: 脳神経疾患; 遺伝子発現; シグナル伝達; 認知症; アルツハイマー病; アミロイド; タウ; リン酸化

Senile plaque and neurofibrillary tangle are pathological hallmarks of brains of Alzheimer's disease. Senile plaque consists of amyloid-beta (Abeta) and neurofibrillary tangle is composed of hyperphosphorylated tau. The mechanism by which Abeta induces hyperphosphorylation of tau remains unclear. In this study, we addressed this question by establishing coculture system in which Abeta-induced hyperphosphorylation of tau is recapitulated. Total RNA was extracted from primary cultured neurons in which hyperphosphorylation of tau is induced by physiologically secreted Abeta by coculture system. By conducting unbiased examination using RNA expression array, we found that expressions in several genes are altred in condition where hyperphosphorylation of tau occurred in primary neurons. Bioinformatics analysis revealed that genes of altered expression affect insulin signaling.

老年斑和神经纤维缠结是阿尔茨海默病的病理特征。老年斑由淀粉样蛋白β（Abeta）组成，神经元缠结由过度磷酸化的tau组成。Abeta诱导tau过度磷酸化的机制仍不清楚。在本研究中，我们通过建立共培养系统来解决这个问题，在该系统中，Abeta诱导的tau蛋白过度磷酸化被重现。从原代培养的神经元中提取总RNA，其中生理分泌的A β通过共培养系统诱导tau过度磷酸化。通过使用RNA表达阵列进行无偏检测，我们发现在初级神经元中发生tau过度磷酸化的情况下，几个基因的表达发生了变化。生物信息学分析表明，基因的表达改变影响胰岛素信号转导。

项目成果

β-amyloid induced hyperphosphorylation of tau : possible involvement of insulin signal dysfunction

β-淀粉样蛋白诱导的 tau 过度磷酸化：可能涉及胰岛素信号功能障碍

• 发表时间: 2011
• 作者: Tokutake T;Kasuga K;Yajima R;Nishizawa M;Ikeuchi T
• 通讯作者: Ikeuchi T

Genotype-phenotype correlations in early onset ataxia with ocular motor apraxia and hypoalbuminemia.

早发性共济失调与眼部运动失用症和低白蛋白血症的基因型-表型相关性。

• 发表时间: 2011
• 期刊: Brain
• 影响因子: 14.5
• 作者: Yokoseki A;Saji E;Arakawa M;Kosaka T;Hokari M;Toyoshima Y;Okamoto K;Takeda S;Sanpei K;Kikuchi H;Hirohata S;Akazawa K;Kakita A;Takahashi H;Nishizawa M;and Kawachi I.;新垣友加里,崎間敦,古波蔵健太郎,仲田清剛,山里正演,石田明夫,安隆則,大屋祐輔,等々力英美;Shiga A et al.;割田仁;市川弥生子,石浦浩之,三井純,松川敬志,田中真生,高橋祐二,後藤順,辻省次;等々力英美,大屋祐輔,佐々木敏;池田将樹，米村公江，藤田行雄，田代裕一，橋本由紀子1，角田聡子，高井恵理子，山崎恒夫，高玉真光，甘利雅邦，針谷康夫，岡本幸市;Yokoseki A et al.
• 通讯作者: Yokoseki A et al.

アルツハイマー病の未病診断

阿尔茨海默病的预诊断

• 发表时间: 2013
• 作者: 白井こころ,等々力英美,菖蒲川由郷;Ichiro Kawachi,三澤仁平,近藤克則;池内健
• 通讯作者: 池内健

アルツハイマー病の発症機構における糖尿病の関与

糖尿病参与阿尔茨海默病的发病机制

• 发表时间: 2011
• 作者: 泉関督人;波多野学;石原一彰;池内健
• 通讯作者: 池内健

Coordinated increase levels of severalγ-secretase product peptides in the CSF of a subpopulation of sporadic Alzheimer's disease subjects

散发性阿尔茨海默病受试者亚群脑脊液中几种γ-分泌酶产物肽水平的协调增加

• 发表时间: 2012
• 期刊: Molecular Neurodegeneration
• 影响因子: 15.1
• 作者: Hata S;Taniguchi M;Piao Y;Ikeuchi T;Fagan AM;Holtzman DM;Bateman R;Gandy S;Urakami K;Suzuki T;Japanese Alzheimer's Disease Neuroimaging Initiatives
• 通讯作者: Japanese Alzheimer's Disease Neuroimaging Initiatives