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Involvement of NUB1 in the early phase of Lewy body disease

Research Project

Project/Area Number 26430050
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionHirosaki University

Principal Investigator

TANJI Kunikazu  弘前大学, 医学研究科, 助教 (10271800)

Co-Investigator(Kenkyū-buntansha) 若林 孝一  弘前大学, 医学研究科, 教授 (50240768)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords脳神経疾患 / レビー小体病 / シャペロン分子 / レビー小体型認知症 / 分解システム / 神経変性 / リン酸化 / 凝集 / 神経変性疾患 / タンパク質分解 / アルツハイマー病 / パーキンソン病
Outline of Final Research Achievements

Abnormal α-synuclein (Syn) is deposited in neuronal cytoplasmic inclusions and presynapses in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Previously we have shown that NUB1 is accumulated in these specific regions together with abnormal Syn and that NUB1 is able to inhibit α-synuclein aggregation in cultured cells. We therefore created transgenic (Tg) mice expressing both NUB1 and abnormal Syn to investigate the role of NUB1 on degradation of abnormal Syn in vivo. Immunohistochemical and biochemical studies confirmed that NUB1 was over-expressed in neurons of mice expressing NUB1 (NUB1 Tg), and both NUB1 and abnormal Syn (double Tg). Normal and abnormal Syn levels were unchanged between abnormal Syn Tg mice (Lewy body disease model mice) and double Tg mice. Pathological observations were almost similar between them. Biochemical analysese showed that level of insoluble Syn were lower in double Tg mice compared with abnormal Syn Tg mice.

Report

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

    (5 results)

All 2016

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (2 results)

  • [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)2016

    • Author(s)
      Klionsky DJ., Abdelmohsen K., Abe A., Abedin MJ.,Inomata M., et al.
    • Journal Title

      Autophagy

      Volume: 12(1) Issue: 1 Pages: 1-222

    • DOI

      10.1080/15548627.2015.1100356

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Alteration of Upstream Autophagy-Related Proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1) in Lewy Body Disease2016

    • Author(s)
      Miki Y, Tanji K, Mori F, Utsumi J, Sasaki H, Kakita A, Takahashi H, Wakabayashi K.
    • Journal Title

      Brain Pathol

      Volume: - Issue: 3 Pages: 359-370

    • DOI

      10.1111/bpa.12297

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The role of NUB1 in alpha-synuclein degradation in Lewy body disease model mice2016

    • Author(s)
      Tanji K, Miki Y, Maruyama A, Mori F, Mimura J, Itoh K, Kamitani T, Wakabayashi K.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 470 Issue: 3 Pages: 635-642

    • DOI

      10.1016/j.bbrc.2016.01.093

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] レビー小体病におけるsynphilin-1結合タンパク質(NUB1)の役割 The role of NUB1 in abnormal alpha-synuclein status in vivo,2016

    • Author(s)
      丹治邦和, 三木康生, 丸山敦史, 森 文秋, 三村純正, 伊東 健, 神谷 哲, 若林孝一
    • Organizer
      第57回日本神経病理学会,
    • Place of Presentation
      ホテルニューキャッスル(青森 弘前市)
    • Year and Date
      2016-06-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] レビー小体病におけるsynphilin-1結合タンパク質(NUB1)の役割2016

    • Author(s)
      丹治邦和, 三木康生, 丸山敦史, 森 文秋, 三村純正, 伊東 健, 神谷 哲, 若林孝一
    • Organizer
      第57回日本神経病理学会
    • Place of Presentation
      ホテルニューキャッスル(青森県・弘前市)
    • Year and Date
      2016-06-01
    • Related Report
      2015 Research-status Report

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

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