Mechanism of presenilin/gamma secretase to produce amyloid beta
Project/Area Number |
26461746
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Psychiatric science
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Research Institution | Osaka University |
Principal Investigator |
Tagami Shinji 大阪大学, 医学系研究科, 助教 (40362735)
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Co-Investigator(Kenkyū-buntansha) |
大河内 正康 大阪大学, 医学系研究科, 講師 (90335357)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | アルツハイマー病 / γセクレターゼ / アミロイドβ / プレセニリン / APL1β / アルツハイマー病バイオマーカー / γ切断 / 脳神経疾患 / バイオマーカー |
Outline of Final Research Achievements |
Beta APP-CTF stubs undergo endoproteolysis by gamma secretase at the epsilon cleavage sites. Gamma secretase sequentially cleaves the resultant substrate every some amino acid residues, thus generating secreted Abeta. We could quantify the small residual peptides generated during sequential cleavages upon Abeta production inside the cells. By this analysis, we could evaluate the activity of gamma secretase to produce amyloid beta. Substantial amounts of Abeta42 accumulate in brains of Presenilin 1 (PS1) mutations-associated with familial AD(FAD). We analyzed CSF APL1beta levels, a non-amyloidogenic surrogate marker of Abeta42 in PS1-FAD patients and in non AD controls. Importantly, CSF APL1beta28 was not significantly higher. However, shorter CSF APL1beta25/27 were significantly lower in PS1-FAD patients. There data suggest that in PS1-FAD patients massive Abeta42 accumulation in PS1-FAD brain occurs without an apparent increase in Abeta42 secretion.
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor.2014
Author(s)
Omi T, Tanimukai H, Kanayama D, Sakagami Y, Tagami S, Okochi M, Morihara T, Sato M, Yanagida K, Kitasyoji A, Hara H, Imaizumi K, Maurice T, Chevallier N, Marchal S, Takeda M, Kudo T.
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Journal Title
Cell Death Dis.
Volume: 5
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Transcriptome analysis of distinct mouse strains reveals kinesin light chain-1 splicing as an amyloid-β accumulation modifier.2014
Author(s)
Morihara T, Hayashi N, Yokokoji M, Akatsu H, Silverman MA, Kimura N, Sato M, Saito Y, Suzuki T, Yanagida K, Kodama TS, Tanaka T, Okochi M, Tagami S, Kazui H, Kudo T, Hashimoto R, Itoh N, Nishitomi K, Yamaguchi-Kabata Y, Tsunoda T, Takamura H, Katayama T, Kimura R, Kamino K, Hashizume Y, Takeda M.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 111
Pages: 2638-2643
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] γセクレターゼの阻害と促進2014
Author(s)
大河内 正康 田上 真次 柳田 寛太 武田 雅俊
Organizer
第33回 日本認知症学会 学術総会
Place of Presentation
パシフィコ横浜 会議センター
Year and Date
2014-11-29 – 2014-12-01
Related Report
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