Molecular pathological environments promoting/inhibiting the development of amyloidosis: the synergistic interaction of protein science and animal models
| 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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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Supersaturation-limited and unlimited phase spaces compete to produce maximal amyloid fibrillation near the critical micelle concentration of sodium dodecyl sulfate.2015
Author(s)
So, M., Ishii, A., Hata, Y., Yagi, H., Naiki, H. and Goto, Y.
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Journal Title
Langmuir
Volume: 31(36)
Issue: 36
Pages: 9973-9982
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] A heterozygous female with Fabry disease due to a novel α-galactosidase A mutation exhibits a unique synaptopodin distribution in vacuolated podocytes.2015
Author(s)
Takahashi N, Yokoi S, Kasuno K, Kogami A, Tsukimura T, Togawa T, Saito S, Ohno K, Hara M, Kurosawa H, Hirayama Y, Kurose T, Yokoyama Y, Mikami D, Kimura H, Naiki H, Sakuraba H, Iwano M.
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Journal Title
Clin Nephrol.
Volume: 83
Issue: 05
Pages: 301-308
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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[Journal Article] Heat of supersaturation-limited amyloid burst directly monitored by isothermal titration calorimetry.2014
Author(s)
Ikenoue, T., Lee, Y.-H., Kardos, J., Yagi, H., Ikegami, T., Naiki, H. and Goto, Y.
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: 111
Issue: 18
Pages: 6654-6659
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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