Elucidation of the role of heparan sulfate 6O-sulfotransferase to the progression of Alzheimer's disease

• Project/Area Number: 18770119
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Aichi Medical University
• Principal Investigator: NAGAI Naoko Aichi Medical University, 分子医科学研究所, 助教 (00367799)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 糖鎖 / ヘパラン硫酸 / ヘパラン硫酸60-硫酸基転移酵素 / アルツハイマー病 / βセクレターゼ / ヘパラン硫酸硫酸基転移酵素 / アミロイドβ前駆体タンパク質 / 細胞内局在 / 酵素 / 脳神経疾患

Research Abstract

アミロイド前駆体タンパク質からアミロイドβペプチドを切り出し、アルツハイマー病の進行に関与するとされる酵素であるβセクレターゼの活性が阻害された場合、ヘパラン硫酸6O-硫酸基転移酵素は小胞体に蓄積した。このとき、ヘパラン硫酸6O-硫酸基転移酵素とアミロイド前駆体タンパク質は共局在し、両者の相互作用が免疫沈降法により確認された。よってアミロイド前駆体タンパク質がヘパラン硫酸6O-硫酸基転移酵素の局在を調節する因子である可能性が示された。

Research Products

• [Journal Article] 6-O-Sulfation of heparan sulfate differentially regulates various fibroblast growth factor-dependent signalings in culture (2008)
  • Author(s): Sugaya N, Habuchi H, Nagai N, Ashikari-Hada S, *Kimata K
  • Journal Title: Journal of Biological Chemistry 283(16) Pages: 10366-10376
  • Peer Reviewed
• [Journal Article] ヘパラン硫酸による高分子リガンドの細胞内取り込み機構 (2008)
  • Author(s): 永井尚子、木全弘治
  • Journal Title: 蛋白質核酸酵素 9月号増刊 Pages: 1564-1569
• [Journal Article] Mice deficient in heparan sulfate 6-O-sulfotransferase-1 exhibit defective heparan sulfate biosynthesis, abnormal placentation, and late embryonic lethality (2007)
  • Author(s): Habuchi H, Nagai N, Sugaya N, Atsumi F, Stevens RL, *Kimata K
  • Journal Title: Journal of Biological Chemistry 282(21) Pages: 15578-15588
  • Peer Reviewed
• [Journal Article] Regulation of heparan sulfate 6-0-sulfation by beta-secretase activity (2007)
  • Author(s): Nagai N, Habuchi H, Kitazume S, Toyoda H, Hashimoto Y, *Kimata K
  • Journal Title: Journal of Biological Chemistry 282(20) Pages: 14942-14951
  • Peer Reviewed
• [Journal Article] Regulation of Heparan Sulfate 6-O-Sulfation by β-Secretase Activity (2007)
  • Author(s): Naoko Nagai
  • Journal Title: Journal of Biological Chemistry 282(20) Pages: 14942-14951
• [Presentation] Regulation of heparan sulfate 6-0-sulfation by b-secretase activity (2008)
  • Author(s): Nagai N
  • Organizer: Gordon Research Conference
  • Place of Presentation: Procter academy, NH, USA
  • Year and Date: 2008-07-06
• [Presentation] Regulation of heparan sulfate 6-O-sulfation by β-secretase activity (2008)
  • Author(s): Naoko Nagai
  • Organizer: Gordon Research Conference
  • Place of Presentation: Procter Academy
  • Year and Date: 2008-07-06
• [Presentation] ヘパラン硫酸6-O-硫酸基転移酵素3(HS6ST3)に結合する細胞内因子の探索 (2007)
  • Author(s): 永井 尚子
  • Organizer: BMB2007
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-14
• [Presentation] ヘパラン硫酸6-0-硫酸基転移酵素HS6ST3の細胞内局在調節機構 (2007)
  • Author(s): 永井尚子
  • Organizer: 第5回糖鎖科学コンソーシアムシンポジウム
  • Place of Presentation: 品川
  • Year and Date: 2007-11-27