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2013 Fiscal Year Final Research Report

Novel pathological pathway of ALS/FTLD-U

Research Project

  • PDF
Project/Area Number 23591254
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionKeio University

Principal Investigator

ITO Daisuke  慶應義塾大学, 医学部, 講師 (80286450)

Project Period (FY) 2011 – 2013
Keywordsubiquitin / optineurin / 筋萎縮性側策硬化症 / endosome / autophagy
Research Abstract

Ubiquilin (UBQLN) 2 localized in endosomal vesicles formed by the ALS-linked molecule optineurin (OPTN) and also co-localized with an initiator of the autophagic process, ULK1, after amino acid starvation. OPTN-vesicles were ubiquitin- and p62-immunopositive. An ALS-linked mutation (E478G) in OPTN abolished vesicle formation. ALS-linked mutations in UBQLN2 additively enhanced UBQLN2 aggregation and formation of inclusion bodies, resulting in mislocation from OPTN-vesicles. UBQLN2 was found to be a potent regulator of the levels of OPTN and the FTD-linked secretory factor progranulin, possibly via the endosomal system, and ALS-linked mutations disturbed these functional consequences. This study demonstrates that ALS-linked mutations in both OPTN and UBQLN2 interfere with the constitution of specific endosomal vesicles, suggesting that the vesicles are involved in protein homeostasis and that these proteins function in common pathological processes.

  • Research Products

    (9 results)

All 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (3 results)

  • [Journal Article] Evidence of TRK-Fused Gene (TFG1) function in the ubiquitin-proteasome system2014

    • Author(s)
      Yagi T, Ito D, Suzuki N
    • Journal Title

      Neurobiol Dis

      Volume: 66C Pages: 83-91

    • Peer Reviewed
  • [Journal Article] Meningoencephalopathy as a clinical manifestation of Epstein–Barr virus-associated hemophagocytic syndrome2013

    • Author(s)
      Koizumi K, Tsukada Y, Ito D, Momoshima S,Okamoto S, Suzuki N
    • Journal Title

      Neurology and Clinical Neuroscience

      Volume: 1(2) Pages: 84-86

    • Peer Reviewed
  • [Journal Article] The human lipodystrophy protein seipin is an ER membrane adaptor for the adipogenic PA phosphatase lipin 12013

    • Author(s)
      Sim MFM, Dennis RJ, Aubry EM, Ramanathan N, Sembongi H, Saudek V, Ito D, O'Rahilly S, Siniossoglou S, Rochford JJ
    • Journal Title

      Molecular Metabolism

      Volume: 2(1) Pages: 38-46

    • Peer Reviewed
  • [Journal Article] Enhanced aggregation of androgen receptor in induced pluripotent stem cell-derived neurons from spinal and bulbar muscular atrophy2013

    • Author(s)
      Nihei Y, Ito D, Okada Y, Akamatsu W, Yagi T, Yoshizaki T, Okano H, Suzuki N
    • Journal Title

      J Biol Chem

      Volume: 288(12) Pages: 8043-52

    • Peer Reviewed
  • [Journal Article] Drug-induced intracranial cystic lesion : a complication of antibiotic treatment via an Ommaya reservoir2013

    • Author(s)
      Yagi T, Osaka M, Ito D, Nihei Y, Ohira T, Takahashi S, Suzuki N
    • Journal Title

      Neurology and Clinical Neuroscience

      Volume: 1(1) Pages: 41

    • Peer Reviewed
  • [Journal Article] Neuroanatomical characterisation of the expression of the lipodystrophy and motor-neuropathy gene Bscl2 in adult mouse brain2012

    • Author(s)
      Garfield AS, Chan WS, Dennis RJ, Ito D, Heisler LK, Rochford JJ
    • Journal Title

      PLoS One

      Volume: 7(9) Pages: e45790

    • Peer Reviewed
  • [Presentation] TDP-43、FUS/TLSとAtaxin2によるALS/FTLD-Uの分子病態2013

    • Author(s)
      伊東大介
    • Organizer
      第32回日本認知症学会
    • Place of Presentation
      長野(学会賞受賞講演)
    • Year and Date
      2013-11-08
  • [Presentation] Progress in disease specific induced pluripotent stem cell research for age-related neurodegenerative disease2013

    • Author(s)
      Ito D
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜(シンポジウム)
    • Year and Date
      2013-09-13
  • [Presentation] Modeling of age-related neurodegenerative diseases with induced pluripotent stem cells2013

    • Author(s)
      Ito D, Suzuki N
    • Organizer
      Neuro2013
    • Place of Presentation
      Kyoto(Symposium)
    • Year and Date
      2013-06-22

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Published: 2015-07-16  

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