| Project/Area Number |
16K09669
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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 |
Neurology
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | アルツハイマー病 / Alzheimer's disease / 神経活動 / neuronal activation / APP processing / Aβ / NMDA受容体 / neuronal activity / APPプロセッシング / アミロイド前駆体蛋白 / アミロイドβ / mRNA / ネットワーク |
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| Outline of Final Research Achievements |
To clarify the association between Alzheimer's pathophysiology and neuronal activity, we analyzed the processing of amyloid precursor protein (APP) under various conditions of glutamatergic activation using primary culture of rat cortical neurons. At 100 μM glutamate, the expression of full-length APP transiently decreased after 2 hours of activation, with decreased APP C-terminal fragment β (CTFβ). In contrast, at 0.1 μM glutamate, the expression of CTFβ increased after 2 hours activation, and levels of Aβ elevated after 24 hours activation. Furthermore, this elevation of Aβ was suppressed by inhibiting the NMDA receptor. These results suggest that suppression of sustained neural activation would be a novel therapeutic target for Alzheimer's disease.
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| Academic Significance and Societal Importance of the Research Achievements |
アルツハイマー病 (AD) の主要な病理変化の一つは神経細胞外に沈着するβ-アミロイド (Aβ)から構成される老人斑である．
本研究は，持続的な神経細胞の興奮がAβ産生亢進を介しAD病態に関与することを示した．さらに，NMDA受容体の阻害によりAβ産生を抑制することを明らかにしたことから，持続的な神経興奮の抑制がADの新たな治療ターゲットとなることが示唆された．
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