2013 Fiscal Year Final Research Report
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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| 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 |
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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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