Analysis of sequential endoproteolytic process of beta-APP to establish novel therapeutic interventions

分析 β-APP 的连续内蛋白水解过程以建立新的治疗干预措施

• 批准号: 17390318
• 负责人: TAKEDA Masatoshi
• 金额: $ 9.6万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390318/
• 关键词: Alzheimer disease; Presenilin; gamma-secretase; Notch signaling; Amyloid-beta peptide; beta-amyloid protein precursor; Notch-1; gamma-cleavage

We have revealed detailed processes of sequential endoproteolysis of betaAPP and Notch. We have found that novel compound-W is a second generation gamma-secretase inhibitor which inhibits Abeta generation without perturbing Notch signaling. Moreover, we found that Abeta29-40 peptide has an activity to inhibit beta-secretase. Furthermore, we established ELISA system to measure Nbeta level in vivo. In addition, we accidentally found compound-OSX which inhibit beta-cleavage of betaAPP without inhibiting BACE.

我们揭示了betaapp和Notch顺序吞噬的详细过程。我们发现，新型化合物W是第二代γ-分泌酶抑制剂，它抑制Abeta的产生而不会扰动Notch信号传导。此外，我们发现Abeta29-40肽具有抑制β-分泌酶的活性。此外，我们建立了ELISA系统以在体内测量NBETA水平。此外，我们不小心发现了化合物OSX，该化合物抑制了βApp的β-裂解而不抑制贝丝。

项目成果

Toll-like receptor 3 mediated ρhyperphosphorylation of tau in human SH-SY5Y neuroblastoma cells

Toll 样受体 3 介导人 SH-SY5Y 神经母细胞瘤细胞中 tau 蛋白的过度磷酸化

• 发表时间: 2006
• 期刊: Psychiatry Clin Neurosci. 60 Suppl 1
• 作者: Nessa BN;Tanaka T;Kamino K;Sadik G;Ansar AB;Kimura R;Tanii H;Okochi M;Morihara T;Tagami S;Kudo T;Takeda M.
• 通讯作者: Takeda M.

Neurobiological studies of dementia-biological markers and neuroprotective strategies for Alzheimer disease.

痴呆症的神经生物学研究-阿尔茨海默病的生物标志物和神经保护策略。

• 发表时间: 2006
• 期刊: Acta Neurol Taiwan 15(1)
• 作者: Tanaka T;Isoe-Wada K;Yamamori H;Kato K;Nessa BN;Sadik GM;Takeda M.
• 通讯作者: Takeda M.

Discrepancy of performance among working memory related tasks in autism spectrum disorders was caused by task characteristics except working memory which could interfere with task execution

自闭症谱系障碍中工作记忆相关任务的表现差异是由工作记忆以外的任务特征引起的，工作记忆可能会干扰任务执行

• 期刊: Psychiatry and Clinical Neuroscience In press
• 作者: Masao Iwase;Akira Shimizu;Masao Iwase et al.;岩瀬真生;岩瀬真生;Takayuki Nakahachi;Takayuki Nakahachi
• 通讯作者: Takayuki Nakahachi

Neural substrates of emotional habituation : A PET study using film stimuli.

情绪习惯的神经基质：使用电影刺激的 PET 研究。

• 期刊: Psychiatry Clin Neurosci(Suppl 1) 60
• 作者: Hatta N;Nishikawa T;Ikejiri Y;Tokunaga H;Masaki Y;Uema T;Kazui H;Doronbekov TK;Ogino A;Miyoshi N;Tanii H;Tanaka T;Oku N;Takeda M.
• 通讯作者: Takeda M.

Neural substrates of emotional habituation:A PET study using film stimuli

情绪习惯的神经基质：使用电影刺激的 PET 研究

• 发表时间: 2006
• 期刊: Psychiatry Clin Neurosci 60 Suppl 1
• 作者: Hatta N;Nishikawa T;Ikejiri Y;Tokunaga H;Masaki Y;Uema T;Kazui H;Doronbekov TK;Ogino A;Miyoshi N;Tanii H;Tanaka T;Oku N;Takeda M.
• 通讯作者: Takeda M.