The development of new diagnostic and therapeutic tools for AD based on regulation of the gamma-secretase complex assembly.
| Project/Area Number |
23590110
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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 |
Biological pharmacy
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| Research Institution | Iwate Medical University |
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Principal Investigator |
MAEDA Tomoji 岩手医科大学, 薬学部, 准教授 (60303294)
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| Co-Investigator(Renkei-kenkyūsha) |
KOMANO Chiaki 岩手医科大学, 薬学部, 教授 (40170378)
TANABE Chiaki 岩手医科大学, 薬学部, 助教 (00552902)
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | プレセニリン複合体 / ニカストリン / シノビオリン / Rer1 / アルツハイマー / アミロイドベータ / 小胞体 / 小胞体関連分解 / OS-9 / アルツハイマー病 / amyloid beta / ユビキチン化 |
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| Research Abstract |
Alzheimer disease is characterized by the deposition of amyloid beta, which is generated from the amyloid precursor protein (APP) through its cleavage by beta- and gamma-secretases. The gamma-secretases complex component nicastrin (NCT) plays significant roles in the assembly and proper trafficking of the gamma-secretases complex and in the recognition of APP. Unassembled NCT is retrieved or retained in the ER by the protein Retention in endoplasmic reticulum 1 (Rer1). We hypothesized, therefore, that Synoviolin (Syvn), an E3 ubiquitin ligase, regulates the assembly or localization of the gamma-secretases complex by ubiquitinating Rer1 resulting in its subsequent degradation. Our findings that the level of Rer1 was increased in Syvn-knockout fibroblasts due to inhibition of its degradation support this hypothesis. Thus, it is likely that Syvn regulates the assembly of the gamma-secretases complex via the degradation of Rer1, which results in the generation of amyloid beta.
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Report
(4 results)
Research Products
(9 results)
