| Project/Area Number |
23390093
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MORI Masayuki 信州大学, 医学系研究科, 准教授 (60273190)
SAWASHITA Jinko 信州大学, 医学系研究科, 助教 (40359732)
KAMETANI Fuyuki 公益財団法人東京都医学総合研究所・認知症, 高次脳機能研究分野, 主席研究員 (70186013)
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| Co-Investigator(Renkei-kenkyūsha) |
HIROSE Masamichi 岩手医科大学, 薬学部, 教授 (40273081)
KAKUTA Sigeru 東京大学, 農学生命科学研究科, 准教授 (80345032)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2011: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | 疾患モデル動物 / アミロイドーシス / 伝播 / 線維形成 / Apolipoprotein A-II / 治療 / マウス / SAA / ApoA-II / トランスジェニックマウス / 小胞体ストレス / アミロイド / コレステロール / ApoA-I |
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| Research Abstract |
Amyloidosis refers to a group of protein folding disorders characterized by accumulation of fine amyloid fibrils. The patients of amyloidoses are increasing and it has been longing for the development of new therapeutic and preventive procedures.
We used animal models of amyloidosis including mouse AApoAII and AA amyloidosis and revealed that 1) Amyloidosis may be transmitted by prion-like infectious process. We found that amyloid fibrils in the feces and blood/blood cells could serve as self-propagating agents for the instigation and progression of amyloidosis. 2) Activated endoplasmic reticulum (ER) stress signals play an important role both in protecting and damaging tissues associated with amyloid deposition. 3) Deficiency of apoliporptein A-I accelerated amyloidosis.
We succeeded in suppressing amyloid deposition in mice by treatment with the C-terminal peptide of type F ApoA-II protein which blocks the active ends of premature amyloid fibrils for self-propagation.
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