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Why is the expression level of BTBD10 in the ALS motor neuron declined?

Research Project

Project/Area Number 24790264
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionTokyo Medical University

Principal Investigator

NAWA Mikiro  東京医科大学, 医学部, 助教 (10398620)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords筋萎縮性側索硬化症 / BTBD10 / 神経変性疾患 / 運動神経細胞死
Outline of Final Research Achievements

Amyotrophic lateral sclerosis(ALS) is a fatal neurodegenerative disease with both upper and lower motor neuronal death. We previously reported that BTBD10, an Akt activator, suppressed ALS-related neuronal cell death. In this study, we focused on the role of BTBD10 in ALS and observed that reduction of expression level of BTBD10 using siRNA leads to caspase dependent cell death in motor neuronal cell line. We also observed neuronal cell death and a locomotive defect in C. elegans lacking BTBD10 gene. Compared with wild type littermates, the expression level of BTBD10 in the surviving motor neurons in spinal anterior horn was declined in G93A-superoxide dismutase 1 transgenic mice. We compared the number of BTBD10-positive motor neurons in spinal cord between sporadic ALS(SALS) patient and non-ALS control. We also observed the number of BTBD10-positive motor neuron was significantly decreased in the surviving motor neurons in the lamina 9 of SALS cases.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (10 results)

All 2014 2013 2012 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (4 results) (of which Invited: 2 results) Remarks (2 results)

  • [Journal Article] KCTD20, a relative of BTBD10, is a positive regulator of Akt.2014

    • Author(s)
      Nawa M, Matsuoka M
    • Journal Title

      BMC Biochem

      Volume: not decided Issue: 1 Pages: 1-7

    • DOI

      10.1186/1471-2091-14-27

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] SH3-binding protein 5 mediates the neuroprotective effect of the secreted bioactive peptide Humanin by inhibiting c-Jun NH2-teminal kinase2013

    • Author(s)
      Takeshita Y, Hashimoto Y, Nawa M, Uchino H, Matsuoka M
    • Journal Title

      J Biol Chem

      Volume: 288 Issue: 34 Pages: 24691-24704

    • DOI

      10.1074/jbc.m113.469692

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Secreted calmodulin-like skin protein inhibits neuronal death in cell-based Alzheimer's disease models via the heterotrimeric Humanin receptor2013

    • Author(s)
      Hashimoto Y, Nawa M, Kurita M, Tokizawa M,Iwamatsu A, Matsuoka M
    • Journal Title

      Cell Death Dis

      Volume: 4 Issue: 3 Pages: 555-555

    • DOI

      10.1038/cddis.2013.80

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduced Expression of BTBD10, an Akt activator, Drives Impairment of Motor Function2012

    • Author(s)
      Nawa M, et al
    • Journal Title

      Cell Death and Differentiation

      Volume: (in press) Issue: 8 Pages: 1398-1407

    • DOI

      10.1038/cdd.2012.19

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] KCTD20, an isoform of BTBD10, is a novel Akt activator.2014

    • Author(s)
      Mikiro Nawa, Masaaki Matsuoka
    • Organizer
      日本薬理学会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] Decreased expression of BTBD10 in ALS motor neurons may contribute to the ALS pathogenesis2012

    • Author(s)
      Mikiro Nawa, Masaaki Matsuoka
    • Organizer
      Society for Neuroscience 42nd annual meeting
    • Place of Presentation
      New Orleans, LO
    • Related Report
      2012 Research-status Report
  • [Presentation] 新規ALS関連分子BTBD10の同定と機能解析ーALS運動神経細胞死機構解明を目指して

    • Author(s)
      名和 幹朗
    • Organizer
      東京線虫勉強会
    • Place of Presentation
      東京大学
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 運動神経細胞における細胞死抑制因子BTBD10発現低下はALS発症の一因である

    • Author(s)
      名和 幹朗、中台 枝里子、三谷 昌平、松岡 正明
    • Organizer
      第169回東京医科大学医学会総会
    • Place of Presentation
      東京医科大学病院
    • Related Report
      2012 Research-status Report
    • Invited
  • [Remarks] 東京医科大学薬理学講座ホームページ

    • URL

      http://www.tokyo-med.ac.jp/pharmacol/top.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 東京医科大学薬理学講座

    • URL

      http://www.tokyo-med.ac.jp/pharmacol/top.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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