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2013 Fiscal Year Final Research Report

Novel therapeutic approaches using the delivery of specific miRNAs for polyglutamine diseases

Research Project

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Project/Area Number 23390231
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionNagoya University

Principal Investigator

ADACHI Hiroaki  名古屋大学, 医学(系)研究科(研究院), 寄附講座准教授 (40432257)

Co-Investigator(Kenkyū-buntansha) SOBUE Gen  名古屋大学, 医学系研究科, 教授 (20148315)
KOIKE Haruki  名古屋大学, 医学部附属病院, 病院講師 (80378174)
TANAKA Fumiaki  横浜市立大学, 医学系研究科, 教授 (30378012)
Research Collaborator MIYAZAKI Yu  名古屋大学, 医学系研究科, 客員研究者
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords球脊髄性筋萎縮症 / アンドロゲンレセプター / CAGリピート / miRNA / CELF2 / 運動ニューロン病
Research Abstract

Spinal and bulbar muscular atrophy (SBMA) is an inherited neurodegenerative disorder caused by the expansion of the polyglutamine (polyQ) tract of the androgen receptor. Recent functional studies have shown the potent activity of specific miRNAs as disease modifiers both in vitro and in vivo. Thus, potential therapeutic approaches that target the miRNA processing pathway have recently attracted attention. We demonstrated a novel therapeutic approach using the adeno-associated virus (AAV) vector;mediated delivery of a specific miRNA for SBMA. We found that miR-196a enhanced the decay of the AR mRNA by silencing CUGBP, Elav-like family member 2 (CELF2). CELF2 directly acted on AR mRNA and enhanced the stability of AR mRNA. Furthermore, we found that the early intervention of miR-196a delivered by an AAV vector ameliorated the SBMA phenotypes in a mouse model. Our results establish the proof of principle that disease-specific miRNA delivery could be useful in neurodegenerative diseases.

  • Research Products

    (8 results)

All 2013 2012 Other

All Journal Article (3 results) Presentation (3 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Genistein, a natural product derived from soybeans, ameliorates polyglutamine-mediated motor neuron disease2013

    • Author(s)
      Qiang Q, Adachi H, Huang Z, Jiang YM, Katsuno M, Minamiyama M, Doi H, Matsumoto S, Kondo N, Miyazaki Y, Iida M, Tohnai G, Sobue G
    • Journal Title

      J Neurochem

      Volume: 126 Pages: 122-130

    • DOI

      10.1111/jnc.12172

  • [Journal Article] p62/SQSTM1 differentially removes the toxic mutant androgen receptor via autophagy and inclusion formation in a spinal and bulbar muscular atrophy mouse model2013

    • Author(s)
      DoiH, AdachiH, KatsunoM, MinamiyamaM, MatsumotoS, KondoN, MiyazakiY, IidaM, TohnaiG, QiangQ, TanakaF, YanagawaT, WarabiE, IshiiT, SobueG
    • Journal Title

      J Neurosci

      Volume: 33 Pages: 7710-7727

    • DOI

      10.1523/JNEUROSCI.3021-12.2013

  • [Journal Article] Viral delivery of miR-196a ameliorates the spinal and bulbar muscular atrophy phenotype via the silencing of CUGBP, Elav-like family member 22012

    • Author(s)
      Miyazaki Y, Adachi H, Katsuno M, Minamiyama M, Jiang YM, Huang Z, Doi H, Matsumoto S, Kondo N, Iida N, Tohnai G, Tanaka F, Muramatsu S, Sobue G
    • Journal Title

      Nat Med 18

      Pages: 1136-1141

    • DOI

      10.1038/nm.2791

  • [Presentation] miR-196aはCELF2の発現抑制を介しSBMAの表現型を有意に改善する2013

    • Author(s)
      宮崎雄, 足立弘明 , 勝野雅央, 村松慎一, 祖父江元
    • Organizer
      第54回日本神経学会総会, 東京都千代田区
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2013-05-31
  • [Presentation] Viral delivery of miR-196a ameliorates the SBMA phenotype via the silencing of CELF22012

    • Author(s)
      Miyazaki Y, Adachi H, Katsuno M, Tanaka F, Muramatsu S, Sobue G
    • Organizer
      Neuroscience 2012
    • Place of Presentation
      New Orleans
    • Year and Date
      2012-10-16
  • [Presentation] miR-196aはSBMAにおいて異常ARmRNAの不安定化を促進し表現型を有意に改善させる2012

    • Author(s)
      宮崎雄, 足立弘明, 勝野雅央, 南山誠, 蒋月梅, 土井英樹, 松本慎二郎, 近藤直英, 飯田円, 藤内玄規, 田中章景, 村松慎一, 祖父江元
    • Organizer
      第53回日本神経学会総会
    • Place of Presentation
      東京千代田区(東京国際フォーラム)
    • Year and Date
      2012-05-24
  • [Book] 球脊髄性筋萎縮症に対する分子標的治療法の開発.すべてがわかるALS・運動ニューロン疾患辻省次, 祖父江元編2013

    • Author(s)
      勝野雅央, 足立弘明, 祖父江元
    • Total Pages
      288-294
    • Publisher
      中山書店
  • [Remarks]

    • URL

      http://www.med.nagoya-u.ac.jp/neurology/research/index.html

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Published: 2015-06-25  

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