| Project/Area Number |
24591272
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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 |
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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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Masaki 京都府立医科大学, 医学研究科, 准教授 (80264753)
徳田 隆彦 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80242692)
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| Co-Investigator(Renkei-kenkyūsha) |
TOKUDA Takahiko 京都府立医科大学, 医学研究科, 教授 (80242692)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | α-シヌクレイン / オートファジー分解 / 凝集体形成 / p62 / オートファジー / リン酸化 / BAG3 / パーキンソン病 |
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| Outline of Final Research Achievements |
The aim of this study is to elucidate the degradation and aggregate formation of α-synuclein associated with Parkinson's disease. α-Synuclein fibrils were introduced into cultured cells, and their degradation was examined immunocytochemically. Autophagy-associated proteins were colocalized to these aggregates. Their degradation was inhibited by knockdown of Atg-5. Moreover, the nucleation activity of α-synuclein fibrils was reduced by inhibition of the lysosomal protein cathepsin B, resulting in a decrease in α-synuclein aggregates. These results suggested that the cleavage of α-synuclein fibrils into lysosomes via autophagy and endocytosis was involved in α-synuclein-aggregate formation.
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