Development of preventive and therapeutic treatments based on the pathogenesis of the transmission of amyloidosis
| Project/Area Number |
26293084
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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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) |
澤下 仁子 信州大学, 学術研究院医学系, 助教 (40359732)
森 政之 信州大学, 学術研究院医学系, 准教授 (60273190)
亀谷 富由樹 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)
矢崎 正英 信州大学, 学術研究院医学系, 准教授 (70372513)
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| Co-Investigator(Renkei-kenkyūsha) |
NAKAMURA Soichiro 信州大学, 役員等, 理事 (00105305)
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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 |
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 実験病理学 / アミロイドーシス / 蛋白質 / 疾患モデル動物 / 伝播 / ApoA-II / トランスサイレチン / 治療 / 老化 / 運動 |
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| Outline of Final Research Achievements |
We investigated mouse AApoAII amyloidosis and in vitro fibril formation to understand the pathogenesis of the transmission of amyloidosis and develop new therapeutic treatments. We revealed that 1) Treatment with the fibril-formation-inhibitory peptide which blocks the active ends of amyloid fibrils for seeding reaction prevented amyloid deposition in amyloidosis induced mice. 2) Amyloid deposition could be induced by the injection of white blood cells (lymphocyte and monocyte) or red blood cells isolated from amyloid-laden mice. 3) Caloric restriction (60% CR) improved ApoA-II metabolism, inflammation and mitochondria function, and suppressed amyloid deposition. 4) Wild and variant TTR amyloid proteins were identified in the small area cut out from tissue sections of patients with accelerated amyloid deposition after domino liver transplantation using laser micro dissection and mass spectrometry analysis.
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Report
(4 results)
Research Products
(80 results)
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[Journal Article] The pathological and biochemical identification of possible seed-lesions of transmitted transthyretin amyloidosis after domino liver transplantaion.2015
Author(s)
Yoshinaga, T, Yazaki M, Sekijima Y, Kametani F, Miyashita K, Hachiya N, Tanaka T, Koaudo N, Higuchi K, Ikeda S.
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Journal Title
J Path: Clin Res 2015
Volume: 1
Issue: 2
Pages: 1-8
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Extracellular deposition of mouse senile AApoAII amyloid fibrils induced different unfolded protein responses in the liver, kidney, and heart.2015
Author(s)
Luo H, Sawashita J, Tian G, Liu Y, Li L, Ding X, Xu Z, Yang M, Miyahara H, Mori M, Qian J, Wang Y, Higuchi K.
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Journal Title
Laboratory Investigation
Volume: 95
Issue: 3
Pages: 320-333
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] 全身性アミロイドの伝播2017
Author(s)
樋口京一
Organizer
第36回日本認知症学会学術集会
Place of Presentation
石川県立音楽堂他（金沢市）
Year and Date
2017-11-24
Related Report
Invited
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[Presentation] 動物のアミロイドーシス2017
Author(s)
樋口京一
Organizer
日本アミロイドーシス研究会第5回学術集会
Place of Presentation
メルパルク京都（京都市）
Year and Date
2017-08-19
Related Report
Invited
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[Presentation] Transgenic mouse models of WT and D76N β2-microglobulin amyloidosis.2015
Author(s)
Miyahara H, Yang M, Igarashi Y, Zhang P, Li L, Sawashita J, Thian G, Mori M, Higuchi K.
Organizer
Mini-workshop on Amyloidosis, Japan-Italy-UK
Place of Presentation
University College London (London, UK)
Year and Date
2015-09-28
Related Report
Int'l Joint Research / Invited
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[Presentation] Deposition of mouse senile AApoAII amyloid fibrils induced unfolded protein responses in the liver, kidney, and heart.2014
Author(s)
Luo H, Sawashita J, Tian G, Liu Y, Li L, Ding X, Xu Z, Yang M, Miyahara H, Mori M, Qian J, Wang Y, Higuchi K.
Organizer
The 14th International Symposium on Amyloidosis.
Place of Presentation
JW Marriott Indianapolis (Indianapolis, USA)
Year and Date
2014-04-27 – 2014-05-02
Related Report
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