Identification and functional analysis of endogenous factors modulating a cutout of Abeta from APP
| Project/Area Number |
25293019
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Nagasaki University |
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Principal Investigator |
IWATA Nobuhisa 長崎大学, 医歯学総合研究科(薬学系), 教授 (70246213)
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| Co-Investigator(Kenkyū-buntansha) |
Asai Masashi 長崎大学, 医歯薬学総合研究科(薬学系), 助教 (90383223)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | アルツハイマー病 / アミロイドβペプチド / γセクレターゼ / プレセニリン / プロテオリシス / 活性調節 / アミロイド前駆体タンパク質 / 神経分化 / γ-セクレターゼ |
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| Outline of Final Research Achievements |
The cause of Alzheimer’s disease is extracellular deposition of amyloid β-peptide (Aβ). Most of Aβ are produced as Aβ40, but Aβ42, which is produced rather in lesser amounts, plays a central role in AD pathogenesis due to its higher aggregation propensity. We previously found that a ratio of Aβ42/Aβ40 production was altered in a differentiation day-dependent manner when we differentiated human iPS cells to neuronal cells, suggesting that gene expression of any factors modulating γ-secretase, which is involved in γ-cleavage of APP-CTFβ, in the cells may be changed during this period. We analyzed changes in gene expression patterns and selected some genes as candidate genes of γ-secretase-modulating factors. We analyzed a ratio of Aβ42/Aβ40 production in cultured medium from cells overexpressing candidate genes. We successfully identified MYT1L and VAT1L as new γ-secretase-modulating factors.
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Report
(4 results)
Research Products
(10 results)
