Histone modification induced by alpha-synuclein
Project/Area Number |
17K09745
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Tohoku University |
Principal Investigator |
Sugeno Naoto 東北大学, 大学病院, 助教 (30509550)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | パーキンソン病 / エピジェネティクス / αーシヌクレイン / αシヌクレイン / ヒストン修飾 / 神経分化 / 免疫沈降 / クロマチン免疫沈降 / alpha-synuclein |
Outline of Final Research Achievements |
Alpha-synuclein (aS) is a key molecule to understand pathomechanisms underlying Parkinson’s disease. Physiological intracellular localization of aS is mainly pre-synaptic membrane, but a part of aS reside nucleus. We focused on the function of aS in nucleus, especially in epigenomic regulation of neuronal genes. At the first step of this project, we tried to find out the aS-interacting proteins in nucleus, and successfully achieved because some of the components of BAF complex that actively work during neuronal differentiation, were significantly bonded with aS. Also, the enzyme that catalyzes histone methylation was also involve in this complex. Interestingly, altered histone modification targeted by the enzyme was enhanced by aS expression in differentiated SH-SY5Y cells. Finally, we identified some neuronal genes affected by the histone methylation.
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Academic Significance and Societal Importance of the Research Achievements |
パーキンソン病発症の最大のリスクは加齢であり、現在進行中の高齢化社会において本疾患への対応は急務となっている。ドパミン補充療法が運動機能改善に役立つものの、一方でドパミン製剤による衝動制御障害は罹患者の生活を破壊しうるものであり発生を未然に防ぐ必要がある。本研究ではαシヌクレインを出発点とした分子生物学的アプローチにより、衝動制御障害のリスクとなりうる遺伝子の発現変化が導かれることを見出した。今後、実臨床へと発展させることにより衝動制御障害のリスクを事前に知ることが可能となると思われる。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Unveiling the coupling of flotillin-1 and extracellular α-synuclein: relevance to dopamine transporter trafficking and Lewy body formation2019
Author(s)
Kobayashi J, Hasegawa T, Sugeno N, Yoshida S, Miki Y, Fukuda M, Kawahata I, Yamakuni T, Tomiyama A, Kawata Y, Ezura M, Kikuchi A, Baba T, Wakabayashi K, Takeda A, Aoki M
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Journal Title
FASEB Journal
Volume: 33
Issue: 9
Pages: 10240-10256
DOI
Related Report
Peer Reviewed
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[Journal Article] Longitudinal changes in 18F-THK5351 PET in corticobasal syndrome2019
Author(s)
Ezura M, Kikuchi A, Ishiki A, Okamura N, Hasegawa T, Harada R, Watanuki S, Funaki Y, Hiraoka K, Baba T, Sugeno N, Oshima R, Yoshida S, Kobayashi J, Kobayashi M, Tano O, Nakashima I, Mugikura S, Iwata R, Taki Y, Furukawa K, Arai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A, Aoki M
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Journal Title
Eur J Neurol
Volume: 26
Issue: 9
Pages: 1205-1211
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.2018
Author(s)
Yoshida S, Hasegawa T, Suzuki M, Sugeno N, Kobayashi J, Ueyama M, Fukuda M, Ido-Fujibayashi A, Sekiguchi K, Ezura M, Kikuchi A, Baba T, Takeda A, Mochizuki H, Nagai Y and Aoki M.
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Journal Title
Hum Mol Genet.
Volume: 27
Issue: 5
Pages: 823-836
DOI
Related Report
Peer Reviewed / Open Access
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