2008 Fiscal Year Final Research Report
Molecular pathogenesis of dialysis-related amyloidosis-A fusion of the in vitro model and the animal model-
Project/Area Number |
18390120
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | University of Fukui |
Principal Investigator |
NAIKI Hironobu University of Fukui, 医学部, 教授 (10227704)
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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)
HIGUCH Keiichi 信州大学, 大学院・医学研究科, 教授 (20173156)
GOTO Yuji 大阪大学, 蛋白質研究所, 教授 (40153770)
|
Project Period (FY) |
2006 – 2008
|
Keywords | 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 / 試験管内分子間相互作用 / トランスジェニックマウス |
Research Abstract |
本研究でわれわれは、長期血液透析患者に発症するβ2-ミクログロブリン(β2-m)アミロイドーシス発症の分子機構解明を目指し、リゾフォスファチジン酸など一部のリゾリン脂質、各種遊離脂肪酸等、陰性荷電を有する生体界面活性分子が、生理的条件下におるβ2-mアミロイド線維の試験管内伸長反応を促進することを明らかにした。また、モデル動物の確立を目指し、ヒトβ2-mトランスジェニックマウスを作成した。
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[Journal Article] Destruction of amyloid fibrils of a β2-microgobulin fragment by laser beam irradiation2009
Author(s)
Ozawa, D., Yagi, H., Ban, T.Kameda, A., Kawakami,T., Naiki, H., Goto, Y.
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Journal Title
J. Biol. Chem 284(2)
Pages: 1009-1017
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[Journal Article] Growth of β2-microglobulin-related amyloid fibrils by non-esterified fatty acids at a neutral pH2008
Author(s)
Hasegawa, K., Tsutsumi-Yasuhara, S., Ookoshi, T., Ohhashi,Y., Kimura, H., Takahashi, N., Yoshida, H., Miyazaki, R., Goto, Y., Naiki, H.
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Journal Title
Biochem.J 416(2)
Pages: 307-315
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[Journal Article] Lysophospholipids induce the nucleation and extension of β2-microglobulin-related amyloid fibrils at a neutral pH2008
Author(s)
Ookoshi, T. Hasegawa, K., Ohhashi, Y., Kimura, H., Takahashi, N., Yoshida, H., Miyazaki, R., Goto, Y., Naiki, H.
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Journal Title
Nephrol. Dial. Transplant 23(10)
Pages: 3247-3255
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[Journal Article] Procollagen C-proteinase enhancer-1(PCPE-1)interacts with β2-microglobulin(β2-m)and may help initiate β2-m amyloid fibril formation in connective tissues2008
Author(s)
Morimoto, H., Wada, J., Font, B., Mott, J.D., Hulmes D.J., Ookoshi, T., Naiki, H., Yasuhara, A., Nakatsuka, A., Fukuoka, K., Takatori, Y., Ichikawa, H., Akagi, S., Nakao, K., Makino, H.
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Journal Title
Matrix Biol 27(3)
Pages: 211-219
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[Journal Article] Cross-seeding and cross-competition in mouse apolipoprotein A-II amyloid fibrils and protein A amyloid fibrils2007
Author(s)
Yan, J., Fu, X., Ge, F., Zhang, B., Yao, J., Zhang, H., Qian, J., Tomozawa, H., Naiki, H., Sawashita, J., Mori, M., Higuchi, K.
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Journal Title
Am.J.Pathol 171(1)
Pages: 172-180
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[Journal Article] A toxic monomeric conformer of the polyglutamine protein.2007
Author(s)
Nagai, Y., Inui, T., Popiel, H.A., Fujikake, N., Hasegawa, K., Urade, Y., Goto, Y., Naiki, H., Toda, T.
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Journal Title
Nat. Struct. Mol. Biol 14(4)
Pages: 332-340
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[Journal Article] The anti-amyloidogenic effect is exerted against Alzheimer's β-amyloid fibrils in vitro by preferential and reversible binding of flavonoids to the amyloid fibril structure2007
Author(s)
Hirohata, M., Hasegawa, K., Tsutsumi-Yasuhara, S., Ohhashi, Y., Ookoshi, T., Ono, K., Yamada, M., Naiki, H.
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Journal Title
Biochemistry 46(7)
Pages: 1888-1899
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[Journal Article] Inhibitors of amyloid β-protein aggregation mediated by GM1-containing raft-like membranes2007
Author(s)
Matsuzaki, K., Noguch, T., Wakabayashi, M., Ikeda, K., Okada, T., Ohashi, Y., Hoshino, M., Naiki, H.
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Journal Title
Biochim. Biophys. Acta-Biomembranes 1768(1)
Pages: 122-130
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[Journal Article] 3D structure of amyloid protofilaments of β2-microglobulin fragment probed by solid-state NMR2006
Author(s)
Iwata, K., Fujiwara, T., Matsuki, Y., Akutsu, H., Takahashi, S., Naiki, H., Goto, Y.
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Journal Title
Proc. Natl. Acad. Sci. U.S.A. 103(48)
Pages: 18119-18124
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[Journal Article] Real-time and single fibril observation of the formation of amyloid β spherulitic structures2006
Author(s)
Ban, T., Morigaki, K., Yagi, H., Kawasaki, T., Kobayashi, A., Yuba, S., Naiki, H., Goto, Y.
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Journal Title
J.Biol.Chem 281(44)
Pages: 33677-33683
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[Journal Article] Conformation of amyloid fibrils of β2-microglobulin probed by tryptophan mutagenesis2006
Author(s)
Kihara, M., Chatani, E., Iwata, K., Yamamoto, K., Matsuura, T., Nakagawa, A., Naiki, H., Goto, Y.
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Journal Title
J.Biol.Chem 281(41)
Pages: 31061-31069
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