Alzheimer's disease: Exploration of combination therapy with food-derived amyloid-beta peptide modulators and environmental therapy.
| Project/Area Number |
26430058
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | Saitama Medical University |
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Principal Investigator |
MORI TAKASHI 埼玉医科大学, 医学部, 教授 (60239605)
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| Research Collaborator |
KOYAMA NAOKI 埼玉医科大学
OKADA SACHIKO 埼玉医科大学
RYUMAE SHINYA 埼玉医科大学
MAEDA MASAHIRO 免疫生物研究所
MARUYAMA NOBUHIRO 免疫生物研究所
TAN JUN University of South Florida
TOWN TERRENCE Keck School of Medicine of the University of Southern California
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | アルツハイマー病 / 遺伝子改変マウス / フェノール化合物 / 抗炎症効果 / 抗酸化効果 / シナプス関連蛋白 / 認知機能 / 行動機能 / 神経病理学 / アミロイドβ蛋白 |
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| Outline of Final Research Achievements |
To examine whether combination therapy further modifies versus single treatment, we treated with an alpha-secretase promotor and a beta-secretase modulator to the model mouse of Alzheimer's disease (AD) (PSAPP mouse). Combination therapy further remediated most behavioral outcome measures versus either single treatment. Moreover, double-treated PSAPP mice had further amelioration of cerebral amyloidosis compared to single treatment alone. Combination therapy elevated nonamyloidogenic soluble APP-alpha and ADAM10, and downregulated expression of amyloidogenic β-carboxyl-terminal APP fragment and BACE1. In concert, the ratio of beta- to alpha-carboxyl-terminal APP fragment was decreased. In toto, combined treatment shifted APP cleavage toward the non-amyloidogenic pathway. Further co-treatment effects included amelioration of neuroinflammation, oxidative stress, and synaptotoxicity. Therefore, we offer preclinical evidence that combination therapy is a promising AD therapeutic approach.
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Report
(5 results)
Research Products
(14 results)
