| Project/Area Number |
22500320
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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 |
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, 准教授 (60239605)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Haruyasu 群馬大学, 医学部, 教授 (00158114)
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| Project Period (FY) |
2010-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥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 / アミロイドβ蛋白 / 神経病理学 / フェノール化合物 / 遺伝子改変マウス / 神経科学 / 神経変性疾患 / ポリフェノール / 細胞・組織 / 獣医学 |
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| Research Abstract |
In the clinical trials for Alzheimer's disease (AD), designer drug approaches have serious negative side effects and adverse events. Thus, we focused on a class of plant or food-derived nutraceuticals with pleiotropic activities as secretase modulators. We orally administered the phenol compounds such as tannic acid (TA) or ferulic acid (FA) to the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes), and evaluated cognitive function and AD-like pathology. Principle findings were that TA or FA could prevent or delay 1) behavioral impairment, 2) cerebral amyloidosis, and 3) neuroinflammation. Moreover, in vitro and cell-free assays showed that the compounds effectively inhibit beta-secretase protein expression and its activity. If results in these pre-clinical mouse models translate to human AD, these findings suggest that dietary supplementation with TA or FA may prevent or delay AD evolution by modulating beta-secretase activity.
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