S1P receptors on neuronal cells as a target of medicine for epilepsy

• Project/Area Number: 24590112
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kobe University
• Principal Investigator: OKADA Taro 神戸大学, 医学(系)研究科(研究院), 准教授 (80304088)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: スフィンゴシン１－リン酸 / スフィンゴ脂質 / スフィンゴシンキナーゼ / エクソソーム / スフィンゴシン１リン酸

Outline of Final Research Achievements

Since it has recently been reported that alpha-synuclein (ASN) in cerebrospinal fluid is a biomarker of epilepsy, we investigated the effect of extracellular ASN on the neuronal cell functions. We found the extracellular ASN causes the inhibition of S1P1 receptor-Gi protein coupling. The ASN effect was subtype specific because it inhibits S1P1 as well as S1P3 receptors but doesn't inhibit S1P2-induced cell signaling. This finding is very important because it was already reported by our group that S1P receptor is involved in the neuronal functions. And this study also suggests the possibility of novel therapeutic strategy for treating epilepsy.

Research Products

• [Journal Article] Sphingosine kinases modulate the secretion of amyloid β precursor protein from SH-SY5Y neuroblastoma cells: the role of α-synuclein. (2014)
  • Author(s): Jesko H, Okada T, Strosznajder RP, Nakamura S.
  • Journal Title: Folia Neuropathol Volume: 52 Pages: 70-78
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes. (2013)
  • Author(s): Taketoshi Kajimoto, Taro Okada, Satoshi Miya, Lifang Zhang, Shun-ichi Nakamura
  • Journal Title: Nature Communications Volume: 4:2712 Issue: 1 Pages: 1-13
  • DOI: 10.1038/ncomms3712
  • Peer Reviewed
• [Presentation] Regulation of multivesicular body maturation by S1P signaling (2013)
  • Author(s): Nakamura, S., Kajimoto, T., Miya, S., Zhang, L., and Okada, T.
  • Organizer: 8th Sphingo-therapy conference
  • Place of Presentation: Yamanakaonsen-Kajikaso Royal Hotel
  • Invited
• [Book] 細胞工学 (2015)
  • Author(s): 梶本武利、岡田太郎、中村俊一
  • Total Pages: 5
  • Publisher: 秀潤社
• [Remarks] 神戸大学大学院医学研究科 生化学・分子生物学講座 生化学分野 研究業績
  • URL: http://www.med.kobe-u.ac.jp/biochemistry/publication.html
• [Remarks] 神戸大学大学院医学研究科生化学・分子生物学講座 生化学分野（中村研究室）
  • URL: http://www.med.kobe-u.ac.jp/biochemistry/Home.html
• [Remarks] 神戸大学医学部生化学分野ホームページ
  • URL: http://www.med.kobe-u.ac.jp/biochemistry/Home.html