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Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization.

Research Project

Project/Area Number 15K08904
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General internal medicine(including psychosomatic medicine)
Research InstitutionUniversity of Fukui

Principal Investigator

Shirafuji Norimichi  福井大学, 学術研究院医学系部門, 助教 (40529319)

Co-Investigator(Kenkyū-buntansha) 濱野 忠則  福井大学, 学術研究院医学系部門, 准教授 (40334817)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsホモシステイン / タウ蛋白 / 神経原線維変化 / タウオパチー / サルコシル不溶性画分のタウ蛋白 / 高ホモシステイン血症 / カスパーゼ
Outline of Final Research Achievements

Hcy activated glycogen synthase kinase 3, a major tau phosphokinase, and inactivated protein phosphatase 2A, a main tau phosphatase. Hcy exhibited cytotoxic effects associated with enhanced activation of caspase. Truncation of tau in the C-terminus, the cleavage site of caspase3 (i.e., D421, detected by the TauC3 antibody) also was increased. Total tau, phosphorylated tau, as well as C-terminal cleaved tau were increased in the sarkosyl insoluble tau fraction. Hcy also increased the level of tau oligomers, as indicated by the tau oligomer complex 1 (TOC1) antibody that specifically identifies oligomeric tau species, in the tris insoluble, sarkosyl soluble fraction.The levels of TOC1-positive oligomeric tau were increased in brain lysate from HHCy mice.
These observations suggest that Hcy increases the levels of phosphorylated tau as well as truncated tau species via caspase3 activation, and enhanced tau oligomerization and aggregation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (5 results)

All 2018 2017 2016

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization.2018

    • Author(s)
      Norimichi Shirafuji,Tadanori Hamano
    • Journal Title

      Molecular Sciences

      Volume: 19 Pages: 891-914

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody-positive paraneoplastic necrotizing myopathy associated with advancee gastric cancer that responded to intravenous immunoglobulin therapy.2017

    • Author(s)
      Yamaguchi T,Matsunaga A,Ikawa M,Shirafuji N
    • Journal Title

      Rinsho Shinkeigaku

      Volume: 28 Pages: 118-123

    • Related Report
      2017 Annual Research Report
    • Open Access
  • [Journal Article] Pioglitazone prevents tau oligomerization.2016

    • Author(s)
      Hamano T, Shirafuji N, Makino C, Yen SH, Kanaan NM, Ueno A, Suzuki J, Ikawa M, Matsunaga A, Yamamura O, Kuriyama M, Nakamoto Y.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 478 Issue: 3 Pages: 1035-1042

    • DOI

      10.1016/j.bbrc.2016.08.016

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Homocysteine Increases Tau Phosphorylation Truncation and Oligomerization.2018

    • Author(s)
      Norimichi Shirafuji
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] HYPOPERFUSION-INDUCED TAU HYPERPHOSPHORYLATION EXTENDS TO THE NON-HYPOPERFUSED AREA IN MOUSE BRAIN.2016

    • Author(s)
      Fujita,Y.,Hamano,T., Shirafuji,N.
    • Organizer
      Alzheimer's Association International Conference (AAIC) 2016
    • Place of Presentation
      Tronto, Canada
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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