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Establishment of the system eliminating amyloid-beta across the blood-brain barrier

Research Project

Project/Area Number 26461271
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionYamaguchi University

Principal Investigator

SANO Yasuteru  山口大学, 医学(系)研究科(研究院), 助教 (20379978)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords血液脳関門 / アルツハイマー病
Outline of Final Research Achievements

The clearance of amyloid β from the brain could be a novel therapeutic target for Alzheimer’s disease (AD). Although LRP1 and ABC transporters were the Aβ transporters at the blood-brain barrier (BBB), conflicting data exist regarding the contribution of these proteins to the clearance of Aß through the BBB. In this study, we examined the expression of LRP1, p-glycoprotein, ABCG2 in the human brain pericytes (HBPCT) and human brain microvascular endothelial cells (HBMECs) using real time PCR, western blot, and immunostaining analyses. LRP1 were mainly expressed in HBPCT, not HBMECs. On the other hand, P-glycoprotein and ABCG2 were predominantly expressed in HBMECs. In addition, we disclosed that RAP, an inhibitor of LRP1, deceased the uptake of FAM-Aβ40 into HBPCT cells. These results indicated that Aβ could be transported across not only HBMEC but also HBPCTs via these receptor and transporter.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (18 results)

All 2017 2016 2015 2014

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (9 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Establishment of a New Conditionally Immortalized Human Skeletal Muscle Microvascular Endothelial Cell Line2017

    • Author(s)
      Sano, H. Sano, Y. Ishiguchi, E. Shimizu, F. Omoto, M. Maeda, T. Nishihara, H. Takeshita, Y. Takahashi, S. Oishi, M. Kanda, T.
    • Journal Title

      Journal of Cellular Physiology

      Volume: 印刷中 Issue: 12 Pages: 3286-3295

    • DOI

      10.1002/jcp.25772

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Astrocytes contribute to Aβ-induced blood brain barrier damage through activation of endothelial MMP9.2017

    • Author(s)
      Spampinato SF, Merlo S, Sano Y, Kanda T, Sortino MA.
    • Journal Title

      J Neurochem.

      Volume: 印刷中 Issue: 3 Pages: 464-477

    • DOI

      10.1111/jnc.14068

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of neuromyelitis optica-IgG at the blood-brain barrier in vitro.2016

    • Author(s)
      Takeshita Y, Obermeier B, Cotleur AC, Spampinato SF, Shimizu F, Yamamoto E, Sano Y, Kryzer TJ, Lennon VA, Kanda T, Ransohoff RM.
    • Journal Title

      Neurol Neuroimmunol Neuroinflamm.

      Volume: 4 Issue: 1

    • DOI

      10.1212/nxi.0000000000000311

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rituximab-associated Progressive Multifocal Leukoencephalopathy Derived from Non-Hodgkin Lymphoma: Neuropathological Findings and Results of Mefloquine Treatment2015

    • Author(s)
      Sano Y, Nakano Y, Omoto M, Takao M, Ikeda E, Oga A, Nakamichi K, Saijo M, Maoka T, Sano H, Kawai M, Kanda T.
    • Journal Title

      Internal Medicine

      Volume: 54 Issue: 8 Pages: 965-970

    • DOI

      10.2169/internalmedicine.54.2308

    • NAID

      130005065265

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sphingosine 1 Phosphate at the Blood Brain Barrier: Can the Modulation of S1P Receptor 1 Influence the Response of Endothelial Cells and Astrocytes to Inflammatory Stimuli?2015

    • Author(s)
      Spampinato SF, Obermeier B, Cotleur A, Love A, Takeshita Y, Sano Y, Kanda T, Ransohoff RM.
    • Journal Title

      PLoS One.

      Volume: 10 Issue: 7 Pages: e0133392-e0133392

    • DOI

      10.1371/journal.pone.0133392

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pertussis Toxin Exploits Specific Host Cell Signaling Pathways for Promoting Invasion and Translocation of Escherichia coli K1 RS218 in Human Brain-derived Microvascular Endothelial Cells.2015

    • Author(s)
      Karassek S, Starost L, Solbach J, Greune L, Sano Y, Kanda T, Kim K, Schmidt MA.
    • Journal Title

      J Biol Chem.

      Volume: 290 Issue: 41 Pages: 24835-24843

    • DOI

      10.1074/jbc.m115.650101

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fingolimod prevents blood-brain barrier disruption induced by the sera from patients with multiple sclerosis.2015

    • Author(s)
      Nishihara H, Shimizu F, Sano Y, Takeshita Y, Maeda T, Abe M, Koga M, Kanda T.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 3 Pages: e0121488-e0121488

    • DOI

      10.1371/journal.pone.0121488

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Markedly Increased IP-10 Production by Blood-Brain Barrier in Neuromyelitis Optica.2015

    • Author(s)
      Shimizu F, Nishihara H, Sano Y, Takeshita Y, Takahashi S, Maeda T, Takahashi T, Abe M, Koga M, Kanda T.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 3 Pages: e0122000-e0122000

    • DOI

      10.1371/journal.pone.0122000

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] An in vitro blood-brain barrier model combining shear stress and endothelial cell/astrocyte co-culture2014

    • Author(s)
      Takeshita Y, Obermeier B, Cotleur A, Sano Y, Kanda T, Ransohoff RM
    • Journal Title

      J Neurosci Methods

      Volume: 232 Pages: 165-72

    • DOI

      10.1016/j.jneumeth.2014.05.013

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 皮膚筋炎の治療における副腎皮質ステロイドの筋微小血管内皮細胞への影響2016

    • Author(s)
      佐野泰照,尾本雅俊,石口絵梨,西原秀昭,竹下幸男,前田敏彦,古賀道明,神田隆
    • Organizer
      第28回日本神経免疫学会学術集会
    • Place of Presentation
      長崎県,長崎市(長崎ブリックホール)
    • Year and Date
      2016-09-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] The effects of glucocorticoid to endomysial microvessels in the treatment for dermatomyositis.2016

    • Author(s)
      Sano Y, Omoto M, Maeda T, Nishihara H, Takeshita Y, Kanda T
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      兵庫県,神戸市(神戸国際会議場)
    • Year and Date
      2016-05-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] Establishment of a new human muscle microvascular endothelial cell line.2016

    • Author(s)
      Sano Y, Omoto M, Kanda T
    • Organizer
      American Academy of Neurology (AAN) 68th Annual Meeting.
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2016-04-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト血液脳関門を介したアミロイドβ蛋白排出におけるABC輸送体の役割2015

    • Author(s)
      佐野 泰照, 前田 敏彦, 安部 真彰, 川井 元晴, 神田 隆
    • Organizer
      第34回日本認知症学会学術集会
    • Place of Presentation
      青森市(リンクステーションホテル青森)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒト筋微小血管内皮細胞の細胞生物学的特徴2015

    • Author(s)
      佐野 泰照, 尾本 雅俊, 佐野 宏徳, 前田 敏彦, 安部 真彰, 西原 秀昭, 神田 隆
    • Organizer
      第27回日本神経免疫学会学術集会
    • Place of Presentation
      岐阜市(長良川国際会議場)
    • Year and Date
      2015-09-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Establishment of a new human muscle microvascular endothelial cell line2015

    • Author(s)
      Yasuteru Sano, Hironori Sano, Toshihiko Maeda, Masaaki Abe, Masatoshi Omoto, and Takashi Kanda
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      新潟市(ホテル日航新潟)
    • Year and Date
      2015-05-20
    • Related Report
      2015 Research-status Report
  • [Presentation] Analysis of factors regulating the expression of AQP4 in human astrocyte2014

    • Author(s)
      Yasuteru Sano, Mariko Oishi, Hiroyo Haruki, Fumitaka Shimizu, Masaaki Abe, and Takashi Kanda
    • Organizer
      12th International Congress of NeuroImmunology
    • Place of Presentation
      Mainz, Germany
    • Year and Date
      2014-11-09 – 2014-11-13
    • Related Report
      2014 Research-status Report
  • [Presentation] Role ATP-binding cassette transporters in efflux of amyloid-β at the human blood-brain barrier2014

    • Author(s)
      Yasuteru Sano, Kazuyuki Saito, Masaaki Abe, Hideaki Nishihara, and Takashi Kanda
    • Organizer
      Neuroscience 2014
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 血液脳関門のAβ蛋白輸送担体を制御する因子の検索2014

    • Author(s)
      佐野泰照,清水文崇,前田敏彦,安部真彰,大石真莉子,佐野宏徳,西原秀昭,神田 隆
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Year and Date
      2014-05-21 – 2014-05-24
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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