Exosome-like synthetic liposomes containing glycosphingolipids for therapy of Alzheimer's disease

• Project/Area Number: 26440041
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Hokkaido University
• Principal Investigator: Yuyama Kohei 北海道大学, 先端生命科学研究院, 特任准教授 (80415546)
• 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: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2015: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
• Keywords: エクソソーム / 細胞外小胞 / アルツハイマー病 / アミロイドbeta / スフィンゴ糖脂質

Outline of Final Research Achievements

Exosome is a subtype of extracellular vesicle, released from various cells including brain neurons. Neuronal cell line (N2a)-derived exosomes can bind amyloid-beta peptide (Abeta) in GSL-dependent manner and clear it through transporting into microglia. In this study, we validated that mouse neuronal exosomes, not glial ones, had abundant GSLs and could capture Abeta. Infusion of the neuronal exosomes into APP transgenic mice decreased Abeta and amyloid depositions, similar to previously reported neuroblastoma-derived exosomes. However, synthetic liposomes containing neuronal GSLs had no potency to bind Abeta. Future challenge is to construct exosome-like liposomes referred to total lipidomics data of neuronal exosomes.

Research Products

• [Journal Article] Exosomes as Carriers of Alzheimer's Amyloid-beta (2017)
  • Author(s): Yuyama K., Igarashi Y.
  • Journal Title: Frontiers in Neuroscience Volume: 印刷中
  • DOI: 10.3389/fnins.2017.00229
  • Peer Reviewed
• [Journal Article] Physiological and Pathological Roles of Exosomes in the Nervous System (2016)
  • Author(s): Yuyama K., Igarashi Y.
  • Journal Title: Biomolecular Concepts Volume: 7 Issue: 1 Pages: 53-68
  • DOI: 10.1515/bmc-2015-0033
  • Peer Reviewed
• [Journal Article] A potential function for neuronal exosomes: sequestering intracerebral amyloid-β peptide. (2015)
  • Author(s): Yuyama K., Sun H., Usuki S., Sakai S., Hanamatsu H., Mioka T., Kimura N., Okada M., Tahara H., Furukawa J., Fujitani N., Shinohara Y., and Igarashi Y.
  • Journal Title: FEBS letters Volume: 589 Pages: 84-88
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Decreased amyloid-beta pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. (2014)
  • Author(s): Yuyama, K., Sun, H., Sakai, S., Mitsutake, S., Okada, M., Tahara, H., Furukawa, J., Fujitani, N., Shinohara, Y. & Igarashi, Y.
  • Journal Title: J Biol Chem Volume: 289 Issue: 35 Pages: 24488-24498
  • DOI: 10.1074/jbc.m114.577213
  • Peer Reviewed / Open Access
• [Presentation] アルツハイマー病予防・治療のためのエクソソーム機能利用 (2017)
  • Author(s): 湯山耕平
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター (宮城県仙台市)
  • Year and Date: 2017-03-08
• [Presentation] アルツハイマー病予防のためのスフィンゴ脂質含有細胞外ベシクル (2016)
  • Author(s): 湯山耕平
  • Organizer: 第９回セラミド研究会学術集会
  • Place of Presentation: 東京ユビキタス協創広場CANVAS (東京都中央区)
  • Year and Date: 2016-10-27
  • Invited
• [Presentation] 神経細胞由来エクソソームのアミロイドbetaクリアランス効果 (2015)
  • Author(s): 湯山耕平, 孫慧, 五十嵐靖之
  • Organizer: 日本認知症学会学術集会
  • Place of Presentation: リンクステーションホール青森(青森県青森市)
  • Year and Date: 2015-10-02
• [Presentation] 神経細胞由来エクソソームのアミロイドbeta蛋白質除去効果 (2014)
  • Author(s): 湯山耕平, 孫慧, 五十嵐靖之
  • Organizer: 第１回日本細胞外顆粒学会
  • Place of Presentation: グランドプリンスホテル広島（広島県広島市）
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] アミロイドbeta蛋白質代謝におけるスフィンゴ糖脂質含有細胞外顆粒エクソソームの役割 (2014)
  • Author(s): 湯山耕平、孫慧、古川潤一、篠原康郎、五十嵐靖之
  • Organizer: 第33回日本糖質学会
  • Place of Presentation: 名古屋大学（愛知県名古屋市）
  • Year and Date: 2014-08-10 – 2014-08-12
  • Invited
• [Remarks] 北海道大学プレスリリース
  • URL: http://www.hokudai.ac.jp/news/140818_pr_pharm.pdf