| Project/Area Number |
22390075
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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 | University of Fukui |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HASEGAWA Kazuhiro 福井大学, 医学部, 助教 (60324159)
OOKOSHI Tadakazu 福井大学, 医学部, 助教 (90362037)
OZAWA Daisaku 福井大学, テニュアトラック推進本部, 助教 (60554524)
BAN Tadato 福井大学, 医学部, 特命助教 (00579667)
HIGUCHI Keiichi 信州大学, 大学院・医学研究科, 教授 (20173156)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2011: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2010: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
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| Keywords | 蛋白質 / 病理学 / 透析アミロイドーシス / β2-ミクログロブリン / アミロイド線維 |
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| Research Abstract |
In order to clarify the molecular pathogenesis of amyloidoses including dialysis -related amyloidosis orβ2-microglobulin (β2-m) amyloidosis, we constructed experimental amyloid fibril formation systems in vivo and in vitro, and then evaluated the roles of the various biological molecules on the amyloid fibril formation. The key findings of this study are as follows: (1) The detailed molecular mechanism of α2-macroglobulin as an extracellular molecular chaperon in the inhibition of β2-microglobulin amyloid fibril formation was clarified. (2) Human β2-m transgenic mice expressing excess amount of β2-m did not showed the amyloid symptom, indicating unknown intrinsic factors are required for the deposition of amyloid fibril in vivo. (3) Toxic effect of the β2-m amyloid fibril on the cultured synovial fibroblast cells was evaluated. (4) We improved the in vitro fibril formation system to investigate the effect of various biological molecules and organic compounds on the fibrillogenesis at near physiological conditions.
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