Characterization of the enzymatic properties of γ-secretase
| Project/Area Number |
17025008
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Doshisha University (2007-2009)
The University of Tokyo (2005-2006) |
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Principal Investigator |
IHARA Yasuo Doshisha University, 生命医科学部, 教授 (60114386)
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| Co-Investigator(Kenkyū-buntansha) |
FUNAMOTO Satoru 同志社大学, 生命医科学部, 准教授 (10345043)
MORISHIMA Maho 北海道大学, 薬学研究院, 特任准教授 (50204722)
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| Project Period (FY) |
2005 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥160,700,000 (Direct Cost: ¥160,700,000)
Fiscal Year 2009: ¥30,000,000 (Direct Cost: ¥30,000,000)
Fiscal Year 2008: ¥30,000,000 (Direct Cost: ¥30,000,000)
Fiscal Year 2007: ¥34,000,000 (Direct Cost: ¥34,000,000)
Fiscal Year 2006: ¥34,000,000 (Direct Cost: ¥34,000,000)
Fiscal Year 2005: ¥32,700,000 (Direct Cost: ¥32,700,000)
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| Keywords | Alzheimer disease / γセクレターゼ / γ切断 / ε切断 / トリペプチド仮説 / アミロイドβタンパク / Aβ産生 / 膜内分解 / アルツハイマー病 / APP / 1型膜タンパク質 / αヘリックス / 脳神経疾患 / 脳・神経 / 認知症 / タンパク質 / 酵素 / アミロイドβタンパク質 |
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| Research Abstract |
How the cleavage proceeds within the membrane has long been enigmatic. We previously hypothesized that βCTF is cleaved first at the membrane-cytoplasm boundary, producing two long Ass, Aβ48 and Aβ49, which are processed further by releasing three residues at each step to produce Aβ42 and Aβ40, respectively. To test this hypothesis, we used LC-MS/MS to quantify the specific tripeptides that are postulated to be released. Using CHAPSO-reconstituted γ-secretase system, we confirmed that Aβ49 is converted to Aβ43/40 by successively releasing two or three tripeptides, and that Aβ48 is converted to Aβ42/38 by successively releasing two tripeptides or these plus an additional tetrapeptide.
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Report
(6 results)
Research Products
(73 results)
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[Journal Article] Effects of human apolipoprotein E isoforms on the amyloid s-protein concentration and lipid composition in brain low-density membrane domains.2007
Author(s)
Morishima-Kawashima M, Han X, Tanimura Y, Hamanaka H, Kobayashi M, Sakurai T, Yokoyama M, Wada K, Nukina N, Fujita SC, Ihara Y
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Journal Title
J Neurochem 101
Pages: 949-958
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Peer Reviewed
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[Journal Article] Effects of human apolipoprotein E isoforms on the amyloid β-protein concentration and lipid composition in brain low-density membrane domains.2007
Author(s)
Morishima-Kawashima M, Han X, Tanimura Y, Hamanaka H, Kobayashi M, Sakurai T, Yokoyama M, Wada K, Nukina N, Fujita SC, Ihara Y
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Journal Title
Journal of Neurochemistry (印刷中)
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[Journal Article] Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease.2006
Author(s)
Kuwano R, Miyashita A, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Kakita A, Takahashi H, Tsukie T, Toyabe S, Akazaw2182a K, Kanazawa I, Ihara Y
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Journal Title
Human Molecular Genetics 5
Pages: 2170-2182
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[Journal Article] Random mutagenesis of presenilin 1 identifies novel mutants exclusively generating long amyloid beta peptides.2005
Author(s)
Nakaya Y, Yamane T, Shiraishi H, Wang HQ, Matsubara E, Sato T, Dolios G, Wang R, De Strooper B, Shoji M, Komano H, Yanagisawa K, Ihara Y, Fraser P, St George-Hyslop P, Nishimura M
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Journal Title
J Biol Chem 280
Pages: 19070-19077
Related Report
Peer Reviewed
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[Presentation] オーバービュー2009
Author(s)
井原康夫
Organizer
日本神経学会総会
Place of Presentation
仙台国際センター(仙台市)
Year and Date
2009-05-20
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[Presentation] Genetic association of dynamin-binding protein gene with late-onset Alzheimer's disease
Author(s)
Kuwano R, Miyashita A, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Kakita A, Takahashi H, Tsukie T, Funamoto S, Toyabe S, Akazawa K, Kanazawa I, Ihara Y
Place of Presentation
Hiroshima
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