2013 Fiscal Year Final Research Report
Drug Discovery of Alzheimer Disease from Molecules- Regulating Microtubule Polymerization
| Project/Area Number |
20228006
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | Tohoku University |
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Principal Investigator |
UCHIDA Takafumi 東北大学, (連合)農学研究科(研究院), 教授 (80312239)
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| Co-Investigator(Kenkyū-buntansha) |
UCHIDA Chiyoko 福島大学, 人間発達文化学類, 教授 (80312776)
YAMASHITA Mari 東北大学, 大学院農学研究科, 教授 (50192430)
HIROSE Keiko 独立行政法人産業技術総合研究所, セルエンジニアリング研究部門, 主任研究員 (90357872)
OKUDA Toru 玉川大学, 学術研究所, 教授 (40328026)
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| Project Period (FY) |
2008-05-12 – 2013-03-31
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| Keywords | 細胞機能 / 発生・分化制御 / タンパク質・糖鎖工学 |
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| Research Abstract |
Based on the hypothesis that Alzheimer disease is caused by the defect of microtubule polymerization, we have studied the functions of the newly identified the microtubule- regulatory molecules, Pin1 and Gas7b (the proteins consisting of the similar sequence to the WW domain of Pin1). We suggested that Pin1 and Gas7b are useful to the diagnosis and treatment of the age-related diseases. We succeeded in establishing the high throughput screening technology for the low molecular inhibitors of Pin1 and identifying DTM, TME-1 and seaweed polyphenol (974B). We showed that Gas7b accelerates microtubule polymerization by binding phosphorylated tau, regulates neuronal cell morphology by regulating the bundling of microtubules and cross linking of microtubule and actin filament, and exists less level in the brains of patients with Alzheimer disease. (original papers; 41)
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[Remarks] 1)リン酸化タンパク質の立体構造を特異的に変化させる酵素Pin1 はアルツハイマ ー病を防御するか? 講師; 内田 隆史
自治医大セミナー (自治医科大学大学院医学研究科 精神医学) 2013 年11 月5 日 ○アウトリーチ活動
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[Remarks] 2) Peptidyl prolyl cis/trans isomerase pin1, target of drug for cancer, infectious disease, Alzheimers disease and diabetes Speaker; Uchida T International Synposium "Science for Society", Dhaka, Bangladesh , Feb. 25, 2012. ○アウトリーチ活動
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[Remarks] 3) "Phosphorylated tau-binding proteins, Pin1 and Gas7 are implicated in Pathogenesis of Alzheimer Disease" Uchida T Albert Einstein College of Medicine , PATHOLOGY RESEARCH SEMINAR March 23, 2010 ○アウトリーチ活動
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[Remarks] 4) 内田隆史、アルツハイマー病に関与する新規因子の生物機能解析 第370 回精神研セミナー (2008 年東京都精神医学総合研究所 5 月25 日) ○アウトリーチ活動
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