Simultaneous control of the production and degradation of Amyloid be-ta by Sphingosine kinase/sphingosine-1-phosphate signaling

• Project/Area Number: 26430059
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Okayama University (2015-2016); Juntendo University (2014)
• Principal Investigator: TAKASUGI NOBUMASA 岡山大学, 医歯薬学総合研究科, 准教授 (60436590)
• Co-Investigator(Renkei-kenkyūsha): TOMITA Taisuke 東京大学, 大学院 薬学系研究科, 教授 (30292957)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: アルツハイマー病 / S1P / SphK2 / 脂質代謝酵素 / アミロイドβ / スフィンゴシンキナーゼ / スフィンゴシン-1-リン酸 / アポリポプロテインE / スフィンゴシン-１-リン酸 / アストロサイト / Sphingosine kinase / Sphingosine-1-phosphate / APP / Amyloid-beta

Outline of Final Research Achievements

Alzheimer disease (AD)is a progressive neurodegenerative disease. The over-production and aggregation of Amyloid beta (Aβ) peptides in brains are considered to be the major pathogenic event for AD. We identified Sphingosine kinase 2 (SphK2) activity is upregulated in AD, and caused to increase the level of Aβ. These results strongly suggest SphK2 and its product sphingosine-1-phosphate are the therapeutic target for AD.

Research Products

• [Journal Article] Consecutive Analysis of BACE1 Function on Developing and Developed Neuronal Cells (2017)
  • Author(s): Kamikubo Y, Takasugi N, Niisato K, Hashimoto Y, Sakurai T
  • Journal Title: J Alzheimers Diｓ Volume: 56 Issue: 2 Pages: 641-653
  • DOI: 10.3233/jad-160806
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Synthetic ceramide analogues increase amyloid-β 42 production by modulating γ-secretase activity. (2014)
  • Author(s): Nobumasa Takasugi; Tomoki Sasaki; Mitsuru Shinohara; Takeshi Iwatsubo; Taisuke Tomita
  • Journal Title: Biochemical and biophysical research communications. Volume: 457 Issue: 2 Pages: 194-199
  • DOI: 10.1016/j.bbrc.2014.12.087
  • Peer Reviewed / Open Access
• [Presentation] APP-βCTF に特異的に結合するエンドソームタンパ ク質の解析 (2016)
  • Author(s): 高杉 展正
  • Organizer: 日本薬学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-03-27
• [Presentation] SphK2/S1P シグナルによるアルツハイマー病治療法の開発 (2016)
  • Author(s): 野田 祐佳、高杉 展正
  • Organizer: 第129回日本薬理学会近畿部会
  • Place of Presentation: 広島県医師会館
• [Presentation] The analysis of endosomal proteins, which specifically interact with APP-βCTF (2015)
  • Author(s): 高杉 展正
  • Organizer: 第128回 日本薬理学会近畿部会
  • Place of Presentation: 千里ライフサイエンスセンター
  • Year and Date: 2015-11-20
• [Presentation] The analysis of endosomal proteins, which specifically interact with APP-βCTF (2015)
  • Author(s): 高杉 展正
  • Organizer: Neuroscience 2015
  • Place of Presentation: McCormick Place in Chicago
  • Year and Date: 2015-10-18
• [Presentation] APP-βCTFに特異的に結合するエンドソームタンパク質の解析 (2015)
  • Author(s): 高杉 展正、 新家 瑠奈、 櫻井 隆
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-19
• [Patent(Industrial Property Rights)] アルツハイマー病予防治療薬のスクリーニング法 (2014)
  • Inventor(s): 高杉 展正、 櫻井 隆、 清水 瑠奈
  • Industrial Property Rights Holder: 高杉 展正、 櫻井 隆、 清水 瑠奈
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-132309
  • Filing Date: 2014-06-17