Structure and function analysis of alpha-synuclein in Parkinson's disease

• Project/Area Number: 26293210
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Osaka University
• Principal Investigator: Mochizuki Hideki 大阪大学, 医学(系)研究科(研究院), 教授 (90230044)
• Co-Investigator(Kenkyū-buntansha): 藤原 悟 国立研究開発法人日本原子力研究開発機構, その他部局等, 研究員 (10354888) ; 八木 寿梓 鳥取大学, 工学(系)研究科(研究院), 助教 (10432494) ; 八木 直人 公益財団法人高輝度光科学研究センター, その他部局等, 研究員 (80133940) ; 荒木 克哉 大阪大学, 医学部附属病院, 医員 (50649431)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
• Keywords: 神経変性疾患 / パーキンソン病 / レビー小体 / αシヌクレイン / 生物物理学 / SPring-8 / J-PARC / 構造解析 / 神経内科学 / アミロイド線維 / 神経科学

Outline of Final Research Achievements

Lewy bodies are deeply involved in the onset of Parkinson 's disease. However, its fine structure is not well understood. We analyzed the fine structure of Lewy bodies in the brain of Parkinson's disease patients using X-ray or infrared ray at a large synchrotron radiation facility (SPring-8) and neutron beam at Japan Proton Accelerator Research Complex (J-PARC). This research using innovative methods revealed the fine structure of Lewy bodies and provided new clues to the development of early diagnosis method and fundamental treatment method.

Research Products

• [Journal Article] A small-angle X-ray scattering study of alpha-synuclein from human red blood cells. (2016)
  • Author(s): Araki K, Yagi N, Nakatani R, Sekiguchi H, So M, Yagi H, Ohta N, Nagai Y, Goto Y, Mochizuki H.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 30473-30473
  • DOI: 10.1038/srep30473
  • NAID: 120006557626
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] “Dynamical Behavior of Human α-Synuclein Studied by Quasielastic Neutron Scattering” (2016)
  • Author(s): Satoru Fujiwara , Katsuya Araki, Tatsuhito Matsuo, Hisashi Yagi, Takeshi Yamada, Kaoru Shibata, Hideki Mochizuki
  • Journal Title: PLoS ONE Volume: 11 Issue: 4 Pages: e0151447-e0151447
  • DOI: 10.1371/journal.pone.0151447
  • Peer Reviewed / Open Access
• [Journal Article] Synchrotron FTIR Micro-Spectroscopy for Structural Analysis of Lewy Bodies in the Brain of Parkinson’s Disease Patients (2015)
  • Author(s): K. Araki, N. Yagi, Y. Ikemoto, S. Choong, H. Hayakawa, G. Beck, H. Sumi, H. Fujimura, T. Moriwaki, Y. Nagai, Y. Goto and H. Mochizuki
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 17625-17625
  • DOI: 10.1038/srep17625
  • NAID: 120006557628
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] The structure analysis for alpha-synuclein and Lewy bodies of Parkinson's disease patients with synchrotron radiation. (2016)
  • Author(s): Katsuya Araki, Naoto Yagi, Rie Nakatani, Hideki Hayakawa, Kousuke Baba, Yuji Goto, Hideki Mochizuki.
  • Organizer: 5th Asian and Oceanian Parkinson’s Disease and Movement Disorders Congress (AOPMC)
  • Place of Presentation: Manila, Philippines
  • Year and Date: 2016-03-11
  • Int'l Joint Research
• [Presentation] The structure analysis for alpha-synuclein and Lewy bodies with synchrotron radiation. (2016)
  • Author(s): Katsuya Araki, Naoto Yagi, Rie Nakatani, Hideki Hayakawa, Kousuke Baba, Yuji Goto, Hideki Mochizuki.
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸コンベンションセンター
• [Presentation] 放射光顕微赤外分光法を用いた剖検脳のグリア細胞内嗜銀性封入体の構造解析． (2016)
  • Author(s): 荒木克哉，八木直人，池中健介，早川英規，永井義隆，藤村晴俊，望月秀樹．
  • Organizer: 第10回パーキンソン病・運動障害疾患コングレス
  • Place of Presentation: 京都ホテルオークラ
• [Presentation] パーキンソン病の新しい治療に向けて ～凝集阻害因子のハイスループットスクリーニング～ (2015)
  • Author(s): 荒木克哉，薮本大紀，宗正智，馬場孝輔，後藤祐児，望月秀樹
  • Organizer: 第33回 日本神経治療学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-11-27
• [Presentation] Synchrotron FTIR micro-spectroscopy for structural analysis of Lewy bodies in the brain of Parkinson’s disease patients. (2015)
  • Author(s): Katsuya Araki
  • Organizer: Australian National University (ANU) & IPR Joint Symposium 2015 “PROTEIN STRUCTURE AND FUNCTION”
  • Place of Presentation: Canberra, Australia
  • Year and Date: 2015-11-10
  • Int'l Joint Research
• [Presentation] The structure analysis for alpha-synuclein and Lewy bodies with synchrotron radiation. (2015)
  • Author(s): Katsuya Araki, Naoto Yagi, Rie Nakatani, Hideki Hayakawa, Kousuke Baba, Yuji Goto, Hideki Mochizuki.
  • Organizer: 第56回 日本神経学会学術大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20
• [Presentation] Structure and function of α-synuclein (2014)
  • Author(s): 望月秀樹
  • Organizer: 日本神経科学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-12
• [Remarks] パーキンソン病発症の鍵を握る「αシヌクレイン」の 生体内により近い状態での構造解析に成功
  • URL: http://www.spring8.or.jp/ja/news_publications/press_release/2016/160808/
• [Remarks] パーキンソン病発症につながる「病態」タンパク質分子の異常なふるまいを発見
  • URL: http://www.qst.go.jp/topics/itemid034-000158.html
• [Remarks] パーキンソン病発症の鍵を握る「αシヌクレイン」の生体内により近い状態での構造解析に成功
  • URL: http://resou.osaka-u.ac.jp/ja/tag_view?tag=%E8%8D%92%E6%9C%A8%E5%85%8B%E5%93%89
• [Remarks] 全自動蛋白凝集検出装置HANABI
  • URL: http://www.protein.osaka-u.ac.jp/physical/HANABI/jp.html