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2011 Fiscal Year Final Research Report

Identification for serum biomarker for ALS associated with the function of TDP-43

Research Project

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Project/Area Number 22659169
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionNiigata University

Principal Investigator

ONODERA Osamu  新潟大学, 脳研究所, 教授 (20303167)

Project Period (FY) 2010 – 2011
Keywords神経分子病態学
Research Abstract

Amyotrophic lateral sclerosis(ALS) is an adult-onset neurodegenerative disease caused by selective loss of motor neurons. In the ALS motor neurons, TAR DNA-binding protein of 43 kDa(TDP-43) is dislocated from the nucleus to cytoplasm and forms inclusions, suggesting that loss of a nuclear function of TDP-43 may underlie the pathogenesis of ALS. TDP-43 functions in RNA metabolism include regulation of transcription, mRNA stability, and alternative splicing of pre-mRNA. However, a function of TDP-43 in tissue affected with ALS has not been elucidated. We sought to identify the molecular indicators reflecting on a TDP-43 function. Using exon array analysis, we observed a remarkable alteration of splicing in several genes as a result of the depletion of TDP-43 expression in two types of cultured cells. In the cells treated with TDP-43 siRNA, wild-type splicing variants decreased and transcripts lacking some exons increased. The RNA binding ability of TDP-43 was necessary for inclusion and exclusion of these exons. Moreover, we found an increment of splicing varinats in motor cortex, spinal cord and spinal motor neurons collected by laser microdissection with ALS. Our results suggest a loss of TDP-43 function in tissues affected with ALS, supporting the hypothesis that a loss of function of TDP-43 underlies the pathogenesis of ALS.

  • Research Products

    (9 results)

All 2012 2011 Other

All Journal Article (3 results) Presentation (6 results)

  • [Journal Article] Co-occurrence of argyrophilic grain disease in sporadic amyotrophic lateral sclerosis2012

    • Author(s)
      Soma K, Fu YJ, Wakabayashi K, Onodera O, Kakita A, Takahashi H
    • Journal Title

      Neuropathology

      Volume: 38 Pages: 54-60

  • [Journal Article] 家族性ALS ALS10(遺伝性ALS-TDP)の臨床と病理2011

    • Author(s)
      今野卓哉, 石原智彦, 西澤正豊, 小野寺理
    • Journal Title

      Clinical Neuroscience

      Volume: 29巻 Pages: 1019-1021

  • [Journal Article] Pri mary lateral sclerosis : Upper-motor-pred ominant amyotrophic lateral sclerosis with frontotemporal lobar degeneration-immunohistochemical and biochemical analyses of TDP-432011

    • Author(s)
      Kosaka T, Fu YJ, Shiga A, Ishidaira H, Tan CF, Tani T, Koike R, Onodera O, Ni shizawa M, Kakita A, Takahashi H
    • Journal Title

      Neuropathology

    • DOI

      doi:10.1111/j.1440-1789.2011.01271.x.

  • [Presentation] Alteration of snRNAs in amyotrophic lateral sclerosis 20112011

    • Author(s)
      T. ISHIHARA, A. SHIGA, A. KAKITA, A. YOKOSEKI, M. NISHIZAWA, H. TAKAHASHI, O. ONODERA
    • Organizer
      米国神経科学会
    • Year and Date
      20110000
  • [Presentation] Aberrant splicing of POLDIP3 gene in motor neuron with ALS2011

    • Author(s)
      A. SHIGA, T. ISHIHARA, A. MIYASHITA, T. KATO, M. KUWABARA, A. YOKOSEKI, R. KUWANO, A. KAKITA, H. TAKAHASHI, M. NISHIZAWA, O. ONODERA
    • Organizer
      米国神経科学会
    • Year and Date
      20110000
  • [Presentation] Alteration of snRNAs in amyotrophic lateral sclerosis2011

    • Author(s)
      T. ISHIHARA, A. SHIGA, A. KAKITA, A. YOKOSEKI, M. NISHIZAWA, H. TAKAHASHI, O. ONODERA
    • Organizer
      6th Brain Research Conference : RNA-Binding Proteins in Neurological Disease
    • Year and Date
      20110000
  • [Presentation] Aberrant splicing of POLDIP3 gene in motor neuron with ALS2011

    • Author(s)
      A. SHIGA, T. ISHIHARA, A. MIYASHITA, T. KATO M. KUWABARA, A. YOKOSEKI, R. KUWANO, A. KAKITA, H. TAKAHASHI, M. NISHIZAWA, O. ONODERA
    • Organizer
      6th Brain Research Conference : RNA-Binding Proteins Neurological Disease
    • Year and Date
      20110000
  • [Presentation] Tardbp欠損マウスのmRNA選択的スプライシングと組織特異的な多様性2011

    • Author(s)
      廣川祥子,佐藤俊哉,石原知彦,藤野赳至,近藤千草,横山峯介,崎村健司,西澤正豊,小野寺理
    • Organizer
      分子生物学会
    • Year and Date
      20110000
  • [Presentation] ALS関連蛋白TDP-43の自己発現調節機能に関与するスプライシング因子の検討

    • Author(s)
      桑原美咲,石原智彦,志賀篤,今野卓哉,小山哲秀,西澤正豊,小野寺理
    • Organizer
      分子生物学会

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Published: 2013-07-31  

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