| Project/Area Number |
25293094
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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 | University of Fukui |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HIGUCHI Keiichi 信州大学, 学術研究院医学系, 教授 (20173156)
HASEGAWA Kazuhiro 福井大学, 医学部, 助教 (60324159)
OZAWA Daisaku 福井大学, テニュアトラック推進本部, 助教 (60554524)
OOKOSHI Tadakazu 福井大学, 医学部, 助教 (90362037)
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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 |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2014: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2013: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
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| Keywords | アミロイドーシス / アミロイド線維 / β2-ミクログロブリン / 細胞外シャペロン / 血清アミロイド成分 / C反応性蛋白質 / 細胞傷害 / トランスジェニックマウス / 血清アミロイドP成分 / 蛋白質 / 病理学 / 透析アミロイド－シス |
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| Outline of Final Research Achievements |
(1) We found that C-reactive protein (CRP) and serum amyloid P component (SAP) may be a member of extracellular chaperones, and the pro- and anti-amyloidogenic activities of SAP are not mutually exclusive, but reflect two sides of the same coin. (2) We found that β2-microglobulin (β2-m) amyloid fibrils endocytosed by the cultured rabbit synovial fibroblasts induce necrosis and apoptosis by disrupting endosomal/lysosomal membranes, proposing a novel mechanism on the cytotoxicity of amyloid fibrils. (3) We histopathologically analyzed the distribution of glycosaminoglycans and proteoglycans in the β2-m amyloid deposits and found the specific distribution patterns of individual molecules. (4) We found that basement membrane components accelerate the initiation of amyloid β-peptide fibril growth in vitro, supporting the essential role of vascular basement membranes in the development of cerebral amyloid angiopathy.
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