| Project/Area Number |
15K14971
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Natural medicines
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| Research Institution | Nagasaki University |
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Principal Investigator |
IWATA Nobuhisa 長崎大学, 医歯薬学総合研究科(薬学系), 教授 (70246213)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | アルツハイマー病 / アミロイドβペプチド / ネプリライシン / αセクレターゼ / βセクレターゼ / カテキン / 結合タンパク質 / カテキン結合タンパク質 / カテキン受容体 |
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| Outline of Final Research Achievements |
I previously found that aliphatic catechin derivatives introduced an alkyl group not only upregulated major Aβ-degrading enzyme neprilysin and α-secretase that cleaves amyloid precursor protein not to generate Aβ, but also downregulated β-secretase via gene expression. In this study, to understand catechin-mediated regulatory mechanism of these gene expressions, I screened catechin-binding proteins for membrane or cytosolic proteins derived from neuronal cells or mouse brains using catechin-coupled magnetic beads and LC/MSMS method, and identified two candidate proteins; one is a secretory vesicle-related protein, and the other is gene expression-related protein. When the neuronal cells overexpressing the candidate protein A or B were treated with aliphatic catechin derivatives, neprilysin activity was more strongly increased than that in mock cells treated with aliphatic catechins, as well β-secrease activity was more prominently suppressed in cells overexpressing the protein A.
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