| Project/Area Number |
16591132
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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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 |
TAGAMI Shinji Osaka University, Graduate School of Medicine, Department of Post-Genomics and Diseases, Assistant, 医学系研究科, 助手 (40362735)
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| Co-Investigator(Kenkyū-buntansha) |
OKOCHI Masayasu Osaka University, Graduate School of Medicine, Department of Post-Genomics and Diseases, Assistant, 医学系研究科, 助手 (90335357)
TAKEDA Masatoshi Osaka University, Graduate School of Medicine, Department of Post-Genomics and Diseases, Professor, 医学系研究科, 教授 (00179649)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | BACE / Aβ degradation / γ-secretase / cell-free BACE assay / cell-free BACE assay |
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| Research Abstract |
Senile plaque is a pathological hallmark of Alzheimer's disease (AD) and its major component is amyloid-beta peptides (Aβ). Either inhibition of Aβ generation or enhancement of Aβ degradation is fundamental approach in developing effective ways to cure AD. We revealed that beta-secretase, which sheds beta-amyloid protein precursor (βAPP) to generate CTF-β, truncates Aβ at two sites. Interestingly, truncated Aβ aggregated much slower than full length Aβ, thus the truncation of Aβ by BACE may promote Aβ degradation. BACE may be utilized as Aβ degrading enzyme if the activity to shed βAPP is selectively inhibited somehow. Moreover, we showed that Aβ peptide inhibited BACE activity at least in vitro. This suggested that Aβ may inhibit BACE activity, which in turn reduces Aβ production. We propose that there might be negative feedback mechanism in Aβ generation cascade.
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