Biological analysis of phosphorylated α-synuclein as a therapeutic target for Parkinson's disease

• Project/Area Number: 19590979
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Yamagata University
• Principal Investigator: ARAWAKA Shigeki Yamagata University, 大学院・医学系研究科, 助教 (00344789)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2008: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2007: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 神経生化学 / 神経病態科学 / 神経変性疾患 / パーキンソン病 / αシヌクレイン / リン酸化 / キナーゼ / 脳神経疾患 / 神経科学

Research Abstract

パーキンソン病(PD)のレビー小体を構成するαシヌクレイン(αS)の129番目セリン残基のリン酸化が、αSの毒性を促進させる可能性がある。本研究課題はαS リン酸化反応を検討し、1)SH-SY5Y細胞でGRK3、GRK5、GRK6、CK2 がリン酸化に関与、2)αSの細胞内局在により寄与するキナーゼが異なる、3)AAVウイルスでαSとキナーゼをラット中脳黒質に共接種しドパミン神経細胞死を生ずる系の作製に成功した。

Research Products

• [Journal Article] Contribution of endogenous G-coupled receptor kinases to Ser129 phosphorylation of -synuclein in HEK293 cells (2009)
  • Author(s): Sakamoto M, Arawaka S (corresponding author), Hara S, Sato H, Cui C, Machiya Y, Koyama S, Wada M, Kawanami T, Kurita K, Kato T
  • Journal Title: Biochem Biophys Res Commun 384 Pages: 378-382
  • Peer Reviewed
• [Journal Article] N-terminal region of alpha-synuclein is essential for the fatty acid-induced oligomerization of the molecules (2008)
  • Author(s): Karube H, Sakamoto M, Arawaka S (corresponding author), Hara S, Sato H, Ren CH, Goto S, Koyama S, Wada M, Kawanami T, Kurita K, Kato T
  • Journal Title: FEBS Lett 582 Pages: 3693-3700
  • Peer Reviewed
• [Journal Article] N-terminal region of alpha-synuclein is essential for the fatty acid-induced oligomerization of the molecules (2008)
  • Author(s): Karube H
  • Journal Title: FEBS letters 582 Pages: 3693-3700
  • Peer Reviewed
• [Presentation] 内因性GRKsおよびCK1εのαシヌクレインSer129リン酸化反応への寄与 (2008)
  • Author(s): 原進、荒若繁樹
  • Organizer: 日本生化学学会・日本分子生物学会合同学会BMB2008
  • Place of Presentation: 神戸
• [Presentation] 内因性GRKsのαシヌクレインSer129リン酸化反応への寄与 (2008)
  • Author(s): 原進、荒若繁樹
  • Organizer: 第49回日本神経学会
  • Place of Presentation: 横浜
• [Presentation] Biological contribution of G-protein-coupled receptor kinases to phosphorylation of alpha-synuclein at S129 in the pathogenesis of sporadic Parkinson's disease (2007)
  • Author(s): Hara S、Arawaka S
  • Organizer: Society of Neuroscience 2007
  • Place of Presentation: サンディエゴ、アメリカ合衆
  • Year and Date: 2007-11-04
• [Presentation] Biological contribution of G-protein-coupled receptor kinases to phosphorylation of alpha-synuclein at Ser129 in pathogenesis of sporadic Parkinson's disease (2007)
  • Author(s): 原 進
  • Organizer: Society of Neuroscience 2007
  • Place of Presentation: アメリカ合衆国
  • Year and Date: 2007-11-04
• [Presentation] Contribution of endogenous GRKs to phosphorylation of alpha-synuclein at S129 in cultured cells (2007)
  • Author(s): Sato H 、Arawaka S
  • Organizer: International psychogeriatric association
  • Place of Presentation: 大阪
  • Year and Date: 2007-10-17
• [Presentation] Contribution of endogenous GRKs to phosphorylation of alpha-synuclein at Ser129 in cultured cells (2007)
  • Author(s): 佐藤 裕康
  • Organizer: International psychogeriatric association 2007
  • Place of Presentation: 大阪
  • Year and Date: 2007-10-17
• [Presentation] GRK5によるα-synucleinセリン129リン酸化に関する細胞生物学的検討 (2007)
  • Author(s): 荒若 繁樹
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-05-17