Elucidation of the pathological upregulation of beta-secretase and its molecular regulation
| Project/Area Number |
25461300
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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 | National Center of Neurology and Psychiatry |
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Principal Investigator |
Araki Wataru 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第6部, 室長 (60311429)
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| Co-Investigator(Renkei-kenkyūsha) |
TAMAOKA AKIRA 筑波大学, 人間総合科学研究科, 教授 (50192183)
SEKIGUCHI MASAYUKI 国立精神・神経医療研究センター 神経研究所, 疾病研究第四部, 室長 (80260339)
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| Research Collaborator |
OGINO KOICHI 大塚製薬Qs'研究所, 主任研究員
LAKSHMANA MADEPALI Torrey Pines Institute for Molecular Studies, Associate Member
KAMETANI FUYUKI 東京都医学総合研究所, 主任研究員
TANOKASHIRA DAISUKE 国立精神・神経医療研究センター 神経研究所, 疾病研究第六部, 流動研究員
MAMADA NAOMI 国立精神・神経医療研究センター 神経研究所, 疾病研究第六部, 研究生
YAMAMOTO FUMIKO 国立精神・神経医療研究センター 神経研究所, 疾病研究第六部, 研究生
ARAKI YUMIKO 国立精神・神経医療研究センター 神経研究所, 疾病研究第六部, 研究生
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥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 / 認知症 / アミロイド / βセクレターゼ / オリゴマー / βアミロイド / BACE1 / 脳神経疾患 |
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| Outline of Final Research Achievements |
The β-secretase BACE1 is an essential protease for production of amyloid β-protein (Aβ), whose expression is aberrantly increased in Alzheimer's disease (AD) brains. Aβ oligomers are suggested to be an inducer of AD pathology. In the present study, we investigated the relationship between BACE1 and Aβ, using a primary neuron model system. We have demonstrated that Aβ oligomers induce BACE1 upregulation through a post-translational mechanism involving its augmentation in neuritic compartments. Our study on the molecular regulation of BACE1 has also revealed that LDL receptor-related protein 1 (LRP1) downregulates BACE1 through modulation of its endosomal transport and lysosomal degradation.
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Report
(4 results)
Research Products
(12 results)
