| Project/Area Number |
16K15478
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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 |
Neurology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Iwatsubo Takeshi 東京大学, 大学院医学系研究科(医学部), 教授 (50223409)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | アルツハイマー病 / 脳インスリン抵抗性 / アミロイドβ / 脳神経疾患 |
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| Outline of Final Research Achievements |
Insulin signaling has been shown to regulate lifespan and the aging process. In this study, we aimed at elucidating the molecular mechanisms how caloric restriction and genetic disruption of IRS-2, the models of retarded aging, suppress amyloid deposition in the brains of Alzheimer’s (AD) model mice. In vivo analyses revealed that neither production nor clearance of soluble Aβ was altered, suggesting that the aggregation process was suppressed in these models. In IRS-2 deficient AD mouse brains, insulin-dependent activation of canonical insulin signaling proteins such as Akt was kept normal. The signaling pathways known to be involved in the anti-aging effect were also unaffected. Based on these results, the existence of an IRS-2-specific, canonical insulin signaling-independent molecular pathway that is responsible for anti-AD effect was suggested.
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