| Project/Area Number |
15602001
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
ポストゲノムのナノサイエンス
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| Research Institution | University of Fukui (2004)
福井医科大学 (2003) |
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Principal Investigator |
HASEGAWA Kazuhiro University of Fukui, Faculty of Medical Sciences, Pathological Sciences, Research Associate, 医学部, 助手 (60324159)
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| Co-Investigator(Kenkyū-buntansha) |
NAIKI Hironobu University of Fukui, Faculty of Medical Sciences, Pathological Sciences, Professor, 医学部, 教授 (10227704)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | amyloid fibril / beta2-mocroglobulin / nano-material / synthetic peptide / conformational change / nanotechnology / beta amyloid / self-assembly / ドデシル硫酸ナトリウム / βアミロイド線維 / 線維形成制御 / 透析アミロイドーシス / 分子間相互作用 / トリフルオロエタノール / グリコサミノグリカン |
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| Research Abstract |
The aims of this study are (1) establishment of general molecular model of amyloid fibril formation and dissociation via the study of beta-amyloid and beta2-microglobulin (β2-m) amyloid (2) elucidation of the effect of various biological molecules or chemical compounds on the common pathogenesis of each amyloidosis, and suggest a strategy for treatment (3) invention of the control method for the formation and dissociation of amyloid fibril, and their application to nanotechnology. Results : (1) six peptides correspond to six of the seven beta sheet in the native structure of β2-m, and examined their amyloidogenisity. Among the peptides examined, peptide(21-31) showed fibril formation. (2) in β2-m amyloid fibril formation, partial unfolding of β2-m is believed to be prerequisite to its assembly into Aβ2M amyloid fibrils. In this study, low concentrations of trifluoroethanol and sodium dodecyl sulfate was found to induce the amyloidogenic partial unfolding of β2-m and result in the extension of Aβ2M amyloid fibrils at a neutral pH. (3) Polyphenols or vitamin A related compounds are found to inhibit the fibril formation of β-amyloid fibrils and to destabilize the preformed fibrils in vitro. (4) a direct thermodynamic analysis of amyloid fibril formation using isothermal titration calorimetry was develpoed. This investigation enables us to measure the heat capacity and enthalpy, and to estimate the stability and structural information on the conformational change of amyloidogenic proteins during fibril formation. As the conclusion of this study, remarkable advance on the clarification of the molecular mechanism of fibril formation in vitro was obtained. Furthermore, useful characteristics of amyloid fibril formation and dissociation for the application to nanotechnology were discovered.
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