| Project/Area Number |
23591704
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Osaka University |
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Principal Investigator |
YANAGIDA Kanta 大阪大学, 医学(系)研究科(研究院), 研究員 (70467596)
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| Co-Investigator(Kenkyū-buntansha) |
OKOCHI Masayasu 大阪大学, 医学(系)研究科(研究院), 講師 (90335357)
TAGAMI Shinji 大阪大学, 医学(系)研究科(研究院), 助教 (40362735)
KODAMA Takashi 大阪大学, 医学(系)研究科(研究院), 研究員 (30512131)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | アルツハイマー病 / アミロイド / セクレターゼ / 脳神経疾患 / アミロイドβ |
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| Research Abstract |
Previously, we detected APLP2-derived Abeta like peptides APL2beta35, 38 and 39 from human Cerebrospinal Fluid. To clarify generation mechanism of APL2beta, APLP2 transfected cells were treated with several secretase inhibitors. Secreted peptides were immunoprecipitated by anti-APL2beta antisera and detected by MALDI-TOF Ms. APL2beta peptides were abolished by beta- and gamma-secretase inhibitors. Conversely, APL2beta38 and 39, but not APL2beta35 were raised by alpha-secretase inhibitor. Interestingly, APL2beta35 was increased, but APL2beta38 and 39 were decreased by overexpression of Neprilysin, which is known as major Abeta degrading enzyme in brain. These results indicate that APL2beta38 and 39 are generated by beta- and gamma-secretase, and cleaved by Neprilysin. Consequently, APL2beta35 is produced. It is considered that Neprilysin is reduced in the brains of Alzheimer disease patients. Thus, APL2beta35 may be a surrogate marker for Abeta degradation by Neprilysin in brain.
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