| Project/Area Number |
15591223
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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 | Mie University |
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Principal Investigator |
TANII Hisashi Mie University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (40346200)
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| Co-Investigator(Kenkyū-buntansha) |
OKAZAKI Yuji Mie University, Faculty of Medicine, Professor, 医学部, 教授 (40010318)
SHIROYAMA Takashi Mie University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (00252354)
TAKEDA Masatoshi Osaka University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00179649)
KUDO Takashi Osaka University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10273632)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | presenilin / APP(Amyloid Precursor Protein) / Alzheimer's Disease / apoptosis / valine / γ-secretase / aluminum / Notch-1 / Notch β |
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| Research Abstract |
Familial Alzheimer disease(FAD)-associated presenilin forming _Y-secretase complex mediates dual transmembraneous cleavage of amyloid precursor protein(APP) (_Y40/42 and _Y49) as well as Notch protein (S3 and S4). APP has an amino acid valine just before _Y40 site (residue 40) and after _Y49 site (residue 50) and the cleavage variety of _Y40/42 is greater than _Y49. In order to investigate the effect of valine upon S4 cleavage site as well as _Y-secretase cleavage, we individually replaced transmembrane domain residue of Notch-1 protein with valine. We observed that all valine-mutated Notch-1 protein have a dominant cleavage site between 1731 and 1732 (S4 site) with slight variations, suggesting that valine does not have major role in _Y-secretase cleavage.
We hypothesized that aluminum may modulate cell viability, axonal transport and neurite outgrowth in APP/PS mutant-bearing cells. Apoptosis was induced Aluminum-maltol treatment in a dose-dependent manner in all cell lines. The APP mutation-bearing cell lines showed significant induction of apoptosis compared to that of wild-type cells. We concluded that aluminum alters cell viability and the axonal transport system in FAD pathogenic mutation-bearing cells.
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