| Project/Area Number |
24700366
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Kyoto University |
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Principal Investigator |
OHNO Mikiko 京都大学, 医学(系)研究科(研究院), 助教 (10583198)
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| Co-Investigator(Renkei-kenkyūsha) |
NISHI Eiichiro 京都大学, 医学研究科, 准教授 (30362528)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | アルツハイマー病 / アミロイドβ / シェディング / αセクレターゼ |
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| Research Abstract |
Amyloid beta peptide, the main component of senile plaques in patients with Alzheimer's disease (AD), is derived from proteolytic cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases. Alpha-cleavage of APP has a potential to preclude the generation of A-beta because it occurs within the A-beta domain. We reported that a metalloendopeptidase, nardilysin (N-arginine dibasic convertase; NRDc) enhances alpha-cleavage of APP, which results in the decreased generation of A-beta in vitro. To clarify the in vivo role of NRDc in AD, we intercrossed transgenic mice expressing NRDc in the forebrain with an AD mouse model. Here we demonstrate that the neuron-specific overexpression of NRDc prevents A-beta deposition in the AD mouse model. The activity of alpha-secretase in the mouse brain was enhanced by the overexpression of NRDc, and was reduced by the deletion of NRDc. Our results indicate that NRDc controls A-beta formation through the regulation of alpha-secretase.
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