Elucidation of characters and neurotoxic mechanisms of alpha-synuclein oligomers and its application to molecular targeted therapy
| Project/Area Number |
23591252
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
TOKUDA Takahiko 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (80242692)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Toshiki 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30264782)
NAKAGAWA Masanori 京都府立医科大学, 医学(系)研究科(研究院), 教授 (50198040)
WATANABE Yoshihisa 京都府立医科大学, 医学(系)研究科(研究院), 講師 (50363990)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | α-シヌクレイン / オリゴマー / 神経細胞毒性 / パーキンソン病 / 分子標的治療 / アルファ・シヌクレイン / 神経細胞変性 / 原子間力顕微鏡 / A30P変異α-シヌクレイン |
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| Research Abstract |
We established the preparing method of alpha-synuclein (A-syn) oligomers and protofibrils by incubating high-concentration solution, 3 mg/mL, of recombinant A-syn with stirring for 7 days at 37 C. Although recombinant A-syn molecules and natural A-syn molecules derived from human CSF were eluted from gel-filtration chromatography at around fractions of 60-70 kDa, those molecules were not dissociated with 8M urea, and accordingly have been demonstrated to exist as monomers in aqueous solution. In cultured cells, intracellular aggregates were formed by adding mixture of recombinant A-syn oligomers and protofibrils into the culture medium, and their degradation was dependent on the autophagy pathway.
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] Knockdown of the Drosophila Fused in Sarcoma (FUS) homologue causes deficient locomotive behavior and shortening of motoneuron terminal branches.2012
Author(s)
Sasayama, H., Shimamura, M., Tokuda, T., Azuma, Y., Yoshida, T., Mizuno, T., Nakagawa, M., Fujikake, N., Nagai, Y. and Yamaguchi, M
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Journal Title
PLoS ONE
Volume: 7(6),
Issue: 6
Pages: e39483-e39483
DOI
Related Report
Peer Reviewed
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[Journal Article] Simultaneous impairment of intracranial and peripheral artery vasoreactivity in CADASIL patients.2012
Author(s)
Fujiwara Y, Mizuno T, Okuyama C, Nagakane Y, Watanabe-Hosomi A, Kondo M, Kuriyama N, Tokuda T, Matsushima S, Nishimura T, Nakagawa M
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Journal Title
Cerebrovascular Diseases
Volume: 33
Issue: 2
Pages: 128-134
DOI
Related Report
Peer Reviewed
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[Presentation] パーキンソニズム患者の髄液プロテオーム解析
Author(s)
徳田隆彦, 石神紀子, 中川正法, 池川雅哉, 近藤誉之, 小森美華
Organizer
第6回パーキンソン病・運動障害疾患コングレス(Movement Disorder Society of Japan)
Place of Presentation
京都
Related Report
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