Role of glycosylation in processing of APP
Project/Area Number |
26460090
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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 |
Biological pharmacy
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Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
Principal Investigator |
Manya Hiroshi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究副部長 (20321870)
|
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 |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 糖鎖 / 脳神経疾患 / 老化 / アルツハイマー病 / アミロイド前駆体タンパク質 |
Outline of Final Research Achievements |
Alterations of the structure or amount of glycans on glycoproteins are associated with many diseases. We previously demonstrated that changes in N-glycans alter Aβ production. Here, we focused on the relationship between Alzheimer’s disease (AD) and O-glycan. The polypeptide N-acetylgalactosaminyltransferase (GALNT) family functions in the first step of mucin-type O-glycan synthesis. Analysis of the expression of GALNTs in the human brain using real-time PCR revealed that the expression of several GALNTs were altered with sporadic AD progression. The expression of GALNT6 increased in AD brain. Transfection of GALNT6 significantly reduced both Aβ40 and Aβ42 secretion. GALNT6 exhibited GalNAc transferase activity on amyloid precursor protein (APP). The activities of α-secretase and β-secretase were not significantly altered in the transfected cells. These data suggest that excess O-glycosylation on APP by GALNT6 inhibits Aβ production.
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Excess APP O-glycosylation by GalNAc-T6 decreases Aβ production.2017
Author(s)
Keiko Akasaka-Manya, Masaki Kawamura, Hiroki Tsumoto, Yuko Saitoh, Yuriko Tachida, Shinobu Kitazume, Hiroyuki Hatsuta, Yuri Miura, Shin-ichi Hisanaga, Shigeo Murayama, Yasuhiro Hashimoto, Hiroshi Manya, Tamao Endo
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Journal Title
J. Biochem.
Volume: 161
Issue: 1
Pages: 99-111
DOI
NAID
Related Report
Peer Reviewed / Acknowledgement Compliant
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