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Investigation of contribution of novel tight junction molecule at the two big central nervous system barriers and its usefulness as a therapeutic target for multiple sclerosis

Research Project

Project/Area Number 16K15475
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionTohoku University

Principal Investigator

Uchida Yasuo  東北大学, 薬学研究科, 助教 (70583590)

Co-Investigator(Renkei-kenkyūsha) TACHIKAWA Masanori  東北大学, 大学院薬学研究科, 准教授 (00401810)
TERASAKI Tetsuya  東北大学, 大学院薬学研究科, 教授 (60155463)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsClaudin-11 / 多発性硬化症 / 血液脳関門 / 血液脊髄関門 / 血液脳脊髄液関門 / 血液クモ膜関門 / 定量プロテオミクス / 密着結合 / 中枢関門 / Claudin11
Outline of Final Research Achievements

Multiple sclerosis is a disorder that autoreactive lymphocytes invade into central nervous system (CNS) and destroy it. The inhibition of disruption of the CNS barriers (which allows the lymphocytes invade into the CNS) is an important therapeutic strategy. However, it remained to be elucidated for the molecular mechanism of CNS barrier breakdown. The present study was the first to clarify that “claudin-11” contributes to the tight junction formation of several CNS barriers and its down-regulation causes the breakdown of CNS barriers in multiple sclerosis.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Int'l Joint Research] Cochin Institute(フランス)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Greifswald(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Cochin Institute(フランス)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Inner Blood-Retinal Barrier Dominantly Expresses Breast Cancer Resistance Protein: class FormattedString { value: Comparative Quantitative Targeted Absolute Proteomics Study of CNS Barriers in Pig }2017

    • Author(s)
      Zhang Z, Uchida Y, Hirano S, Ando D, Kubo Y, Auriola S, Akanuma S, Hosoya K, Urtti A, Terasaki T, Tachikawa M
    • Journal Title

      Mol Pharm

      Volume: 14 Issue: 11 Pages: 3729

    • DOI

      10.1021/acs.molpharmaceut.7b00493

    • URL

      https://localhost/en/publications/fff2583f-3733-4491-8bbc-e7c2c6066534

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Actin filament-associated protein 1 (AFAP-1) is a key mediator in inflammatory signaling-induced rapid attenuation of intrinsic P-gp function in human brain capillary endothelial cells.2017

    • Author(s)
      Yutaro Hoshi, Yasuo Uchida, Masanori Tachikawa, Sumio Ohtsuki, Tetsuya Terasaki
    • Journal Title

      Journal of Neurochemistry

      Volume: 印刷中 Issue: 2 Pages: 247-262

    • DOI

      10.1111/jnc.13960

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 多発性硬化症における中枢関門の破綻への新規密着結合分子claudin-11 の寄与の解明2018

    • Author(s)
      内田康雄, 住谷智仁, 立川正憲, 山川達也, 村田将, 八木悠太, 佐藤和貴, 伊藤克彰, 大槻純男, Pierre-Olivier Couraud, 鈴木貴, 寺崎哲也
    • Organizer
      日本薬剤学会第33 年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 中枢関門の密着結合形成におけるclaudin-11の寄与と多発性硬化症におけるその発現低下の解明2018

    • Author(s)
      住谷智仁、内田康雄、山川達也、村田将、八木悠太、佐藤和貴、伊藤克彰、立川正憲、大槻純男、鈴木貴、寺崎哲也
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脳転移性メラノーマ細胞由来exosomesによるヒト脳毛細血管内皮細胞株hCMEC/D3のエネルギー代謝抑制制御2017

    • Author(s)
      TRAN Quynh-Phuong、内田康雄、黒田広樹、梅津美奈、八木悠太、立川正憲、寺崎哲也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 中枢関門におけるandrogen刺激に応答したclaudin-11発現調節作用の解明と血液クモ膜関門におけるclaudin-11の発現解析2017

    • Author(s)
      住谷智仁、内田康雄、 山川達也、村田将、張正宇、立川正憲、大槻純男、寺崎哲也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] LC-MS/MS-based research for Blood-Brain Barrier and Malignant Brain Tumor2017

    • Author(s)
      Uchida Y
    • Organizer
      Seminar in Institute for Research in Biomedicine, University of Barcelona
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ブタBRB, BBB及びBCSFBの輸送担体の絶対発現量解析:BCRPの重要性2017

    • Author(s)
      張正宇、内田康雄、平野誠巳、安藤大介、久保義行、 Seppo Auriola、赤沼伸乙、立川正憲、細谷健一、Arto Urtti、寺崎哲也
    • Organizer
      日本薬剤学会第32年会 (最優秀発表賞受賞)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of label free comprehensive absolute quantification method by SWATH-MS combined with in silico peptide selection criteria ~Its application for the hepatic drug delivery~2017

    • Author(s)
      平野誠巳、内田康雄、立川正憲、後藤諒平、寺崎哲也
    • Organizer
      日本薬物動態学会第32回年会(優秀口頭発表賞受賞)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Proteomics based characterization of the blood-spinal cord barrier transporters in rats: Comparison with the blood-brain barrier2017

    • Author(s)
      八木悠太、立川正憲、内田康雄、寺崎哲也
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Next generation quantitative proteomics “SWATH 法” の基礎と応用2016

    • Author(s)
      内田康雄
    • Organizer
      第12 回 東北大学学際科学フロンティア研究所FRIS セミナー
    • Place of Presentation
      仙台
    • Year and Date
      2016-08-10
    • Related Report
      2016 Research-status Report
    • Invited
  • [Remarks] 研究業績

    • URL

      http://www.pharm.tohoku.ac.jp/~soutatsu/dds/profile/uchida.htm

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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