Development of apomorphine therapy targeting insulin resistance in Alzheimer's disease
| Project/Area Number |
26461274
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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 | Ehime University (2015-2016)
Kyushu University (2014) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山崎 亮 九州大学, 医学研究院, 准教授 (10467946)
飯沼 今日子 (本村 / 飯沼 今日子(本村今日子)) 九州大学, 医学部, 臨床・衛生検査技師 (20380644)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | アルツハイマー病 / 糖尿病 / モデルマウス / アポモルフィン / アミロイドβ蛋白 / 毒性ターン / リン酸化タウ蛋白 / 3xTg-ADマウス / 記憶障害 / インスリン分解酵素 / インスリン受容体基質 / 記憶機能 / インスリン抵抗性 / インスリン分泌能 |
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| Outline of Final Research Achievements |
Alzheimer’s disease (AD) is the major cause of dementia. A diabetes-like pathogenic mechanism in AD brain has recently been suggested, and AD is called “type-3 diabetes mellitus (DM)”. Previously, we identified apomorphine (APO) as a novel drug to promote degradation of Aβ42 accumulating in AD neurons. APO may improve the insulin resistance in AD neurons. In the present study, we established DM+AD mouse models in which injection of streptozotocin (STZ) induced type-1 DM and high-fructose diet (HFuD) induced type-2 DM in 3xTg-AD mice. Exacerbation of cognitive impairment and increases in the toxic turn Aβ42 which forms readily aggregating oligomers were more apparent in STZ-injection mice (type-1 DM) than in HFuD mice. In addition, it was indicated that toxic turn Aβ42 co-aggregates with tau oligomers in neurons. Thereafter, we will develop new therapeutic strategies of combination of APO and other DM drugs using such a DM+AD mouse models.
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Report
(4 results)
Research Products
(30 results)
