Regulation of APP phosphorylation
| Project/Area Number |
24790260
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General pharmacology
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| Research Institution | Nagasaki University |
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Principal Investigator |
ASAI Masashi 長崎大学, 医歯薬学総合研究科(薬学系), 助教 (90383223)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | アルツハイマー病 / ダウン症 / APP / リン酸化 / DYRK1A / RCNA1 / ネプリライシン / RCAN1 / 21番染色体 / 第21番染色体 / アミロイドβペプチド / タウ / キナーゼ / ホスファターゼ |
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| Outline of Final Research Achievements |
To treat Alzheimer's disease, it is required to reduce the amount of amyloid-β peptide in the brain. γ-Secretase prefer phosphorylated C-terminal fragments of precursor protein of amyloid-β peptide (APP) as a substrate. To identify the molecules related with APP phosphorylation, DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A) and RCAN1 (regulator of calcineurin 1) on chromosome 21 were focused. Overexpression of DYRK1A leaded to APP and tau phosphorylation, while overexpression of RCAN1 leaded to tau phosphorylation, but not APP. Moreover, overexpression of either or both leaded to decrease in the peptidase activity of neprilysin and increase in of the phosphorylation of neprilysin. Treatment of a DYRK1A inhibitor reduced Aβ levels in the medium. These results suggest that DYRK1A and RCAN1A are potential targets of drug development to treatment of Alzheimer's disease.
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Cathepsin K-mediated Notch1 activation contributes to neovascularization in response to hypoxia2014
Author(s)
Jiang H, Cheng XW, Shi GP, Hu L, Inoue A, Yamamura Y, Wu H, Takeshita K, Li X, Huang Z, Song H, Asai M, Hao CN, Unno K, Koike T, Oshida Y, Okumura K, Murohara T, Kuzuya M
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Journal Title
Nat Commun
Volume: 5
Issue: 1
Pages: 3838-3838
DOI
Related Report
Peer Reviewed
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[Journal Article] A drug screening platform for Alzheimer's disease with intracellular Aβ oligomers using patient-specific iPSCs2013
Author(s)
Kondo, T., (他24名), Murakami, K., Irie, K., Klein, W. L., Mori, H., Asada, T., Takahashi, R., Iwata, N., Yamanaka, S., Inoue, H
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Journal Title
Cell Stem Cell
Volume: 12
Issue: 4
Pages: 487-496
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Modeling Alzheimer’s disease using iPS cells reveals stress phenotypes associated with intracellular β-amyloid oligomer and differential drug responsiveness2013
Author(s)
Asai M, Kondo T, Shirotani K, Tsukita K, Watanabe K, Maruyama K, Murakami K, Irie K, Klein WL, Mori H, Asada T, Inoue H, Iwata N
Organizer
Alzheimer’s Association International Conference 2013
Place of Presentation
Boston Convention and Exhibition Center, Boston, MA (USA)
Related Report
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[Presentation] Modeling Alzheimer’s disease using induced pluripotent stem cells from familial and sporadic Alzheimer’s disease patients2013
Author(s)
Shirotani K, Kondo T, Asai M, Tsukita K, Watanabe K, Maruyama K, Murakami K, Irie K, Klein WL, Mori H, Asada T, Inoue H, Iwata N
Organizer
Alzheimer’s Association International Conference 2013
Place of Presentation
Boston Convention and Exhibition Center, Boston, MA (USA)
Related Report
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