Integrative pathology of Amyloidosis: Exploratory research on the basis of transmission phenomena
| Project/Area Number |
17H04063
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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) |
森 政之 信州大学, 学術研究院医学系, 准教授 (60273190)
矢崎 正英 信州大学, 学術研究院保健学系, 教授 (70372513)
宮原 大貴 信州大学, 先鋭領域融合研究群バイオメディカル研究所, 助教(特定雇用) (90823287)
澤下 仁子 信州大学, 学術研究院医学系, 助教 (40359732)
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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2017: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 実験病理学 / アミロイドーシス / 疾患モデル動物 / 老化 / 蛋白質化学 / マウス / 伝播 / リポ蛋白質 / 疾患モデル動 / 蛋白質 / ApoA-II / アミロイド / 病理学 |
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| Outline of Final Research Achievements |
We investigated "Prion like transmission" and "Age-related disruption of proteostasis" of amyloidosis using mouse AApoAII amyloidosis.
We found fibrillar molecules having amyloidosis inducing activity in white blood cells and serum of amyloid laden mice, and amyloid fibrils made of short ApoA-II without C-terminal in intestine in which the earliest deposition is observed. We believe that more amyloidogenic N-terminal ApoA-II fragments polymerize to amyloid fibri firstl in intestine and blood transports these fibrils to other organs in which fibrils works as templates for full length ApoA-II to make amyloid fibrils.
We used calorie restriction, exercise and treatment with anti-oxidative stress reagents for decelerating aging and revealed that these treatments prevented amyloidosis significantly, We investigated the age-related amyloidosis of C57BL/6 mice that is a standard mouse strain for aging research in various institutes.
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| Academic Significance and Societal Importance of the Research Achievements |
30種類以上報告されているアミロイドーシスには、アミロイド線維がseedとして作用し、自己増殖するという「伝播現象」と、年齢（老化）が最も大きな発症危険因子であるという「共通点」が認められている。本研究では、血球及び血漿中に伝播力を持つ物質が存在すること、腸管で末端が切断されたアミロイド原性が高い前駆タンパク質が最初にアミロイド線維を形成し、その後全身へ伝播することを示したことは、アミロイドーシスに共通した発症抑制方法の開発での意義は大きい。高齢化の進行が進む現状において、老化を遅延させる食事制限、運動、抗酸化剤の投与などが、アミロイドーシスの発症を抑制することを示したことは社会的意義が高い。
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Report
(4 results)
Research Products
(48 results)
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[Journal Article] Amyloidosis-inducing activity of blood cells in mouse AApoAII amyloidosis2018
Author(s)
Ding X, Liu Y, Yang M, Li L, Miyahara H, Dai J, Xu Z, Matsumoto K, Mori M, Higuchi K, Sawashita J.
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Journal Title
Experimental Animals
Volume: 67
Issue: 2
Pages: 105-115
DOI
NAID
ISSN
0007-5124, 1341-1357, 1881-7122
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comprehensive proteomic profiles of mouse AApoAII amyloid fibrils provide insights into the involvement of lipoproteins in the pathology of amyloidosis2018
Author(s)
Miyahara H, Sawashita J, Ishikawa E, Yang M, Ding X, Liu Y, Hachiya N, Kametani F, Yazaki M, Mori M, Higuchi K
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Journal Title
J Proteomics
Volume: 172
Pages: 111-121
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Amyloidosis-inducing activity of blood components in mouse AApoAII amyloidosis.2018
Author(s)
Xin Ding, Yingye Liu, Mu Yang, Lin Li, Hiroki Miyahara, Jian Dai, Zhe Xu, Kiyoshi Matsumoto, Masayuki Mori, Jinko Sawashita, Keiichi Higuchi
Organizer
The XVIth International Symposium on Amyloidosis
Related Report
Int'l Joint Research
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