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Dock family proteins in demyelination and neuroinflammation

Research Project

Project/Area Number 25640043
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

NAMEKATA Kazuhiko  公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 副参事研究員 (70392355)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsDock3 / 脱髄疾患 / 神経変性 / Dock8 / Dockファミリー / 視神経炎症 / EAE
Outline of Final Research Achievements

Oligodendrocytes are the myelinating cells of axons in the central nervous system and these cells are damaged in demyelinating disorders including multiple sclerosis (MS) and optic neuritis. We examined if Dock3 can suppress demyelination in a cuprizone-induced demyelination model, an animal model of MS. We demonstrate that Dock3 overexpression protects myelin in the corpus callosum following cuprizone treatment. Furthermore, we show that cuprizone demyelinates optic nerves and the extent of demyelination is ameliorated in mice overexpressing Dock3. Cuprizone treatment impairs visual function, which was demonstrated by multifocal electroretinograms, an established non-invasive method, and Dock3 overexpression prevented this effect. In mice overexpressing Dock3, Erk activation is increased, suggesting this may at least partly explain the observed protective effects. Our findings suggest that Dock3 may be a therapeutic target for demyelinating disorders.

Report

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

    (28 results)

All 2015 2014 2013 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 8 results,  Acknowledgement Compliant: 11 results) Presentation (12 results) (of which Invited: 2 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury.2015

    • Author(s)
      Noro, T., Namekata, K., Kimura, A., Guo, X., Azuchi, Y., Harada, C., Nakano, T., Tsuneoka, H. and Harada, T.
    • Journal Title

      Cell Death and Disease

      Volume: 6 Issue: 4 Pages: e1720-e1720

    • DOI

      10.1038/cddis.2015.93

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Valproic acid prevents NMDA-induced retinal ganglion cell death via stimulation of neuronal TrkB receptor signaling2015

    • Author(s)
      Kimura, A., Namekata, K., Guo, X., Noro, T., Harada, C. and Harada, T.
    • Journal Title

      American Journal of Pathology

      Volume: 185 Issue: 3 Pages: 756-764

    • DOI

      10.1016/j.ajpath.2014.11.005

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Brimonidine suppresses loss of retinal neurons and visual function in a murine model of optic neuritis2015

    • Author(s)
      Guo, X., Namekata, K., Kimura, A., Noro, T., Azuchi, Y., Semba, K., Harada, C., Yoshida, H., Mitamura, Y. and Harada, T.
    • Journal Title

      Neuroscience Letters

      Volume: 592 Pages: 27-31

    • DOI

      10.1016/j.neulet.2015.02.059

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Valproic acid prevents retinal degeneration in a murine model of normal tension glaucoma2015

    • Author(s)
      Kimura, A., Guo, X., Noro, T., Harada, C., Tanaka, K., Namekata, K. and Harada, T
    • Journal Title

      Neuroscience Letters

      Volume: 588 Pages: 108-113

    • DOI

      10.1016/j.neulet.2014.12.054

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Expression of intraocular peroxisome proliferator-activated receptor gamma in patients with proliferative diabetic retinopathy.2015

    • Author(s)
      Katome T, Namekata K, Mitamura Y, Semba K, Egawa M, Naito T, Harada C, Harada T
    • Journal Title

      J Diabetes Complications

      Volume: 29 Issue: 2 Pages: 275-281

    • DOI

      10.1016/j.jdiacomp.2014.10.010

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Arundic acid attenuates retinal ganglion cell death by increasing glutamate/aspartate transporter expression in a model of normal tension glaucoma.2015

    • Author(s)
      Yanagisawa, M., Aida, T., Takeda, T., Namekata, K., Harada, T., Shinagawa, R. and *Tanaka. K.
    • Journal Title

      Cell Death and Disease

      Volume: 6 Issue: 3 Pages: e1693-e1693

    • DOI

      10.1038/cddis.2015.45

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Renin-angiotensin system regulates neurodegeneration in a mouse model of normal tension glaucoma2015

    • Author(s)
      Semba, K., Namekata, K., Guo, X., Harada, C., Harada, T. and Mitamura, Y
    • Journal Title

      Cell Death and Disease

      Volume: 5 Issue: 7 Pages: e1333-e1333

    • DOI

      10.1038/cddis.2014.296

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dock3 protects myelin in the cuprizone model for demyelination.2014

    • Author(s)
      Namekata K, Kimura A, Harada C, Yoshida H, Matsumoto Y, Harada T.
    • Journal Title

      Cell Death Dis.

      Volume: 5 Issue: 8 Pages: e1395-e1395

    • DOI

      10.1038/cddis.2014.357

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma.2014

    • Author(s)
      Semba K, Namekata K, Kimura A, Harada C, Mitamura Y, Harada T
    • Journal Title

      Cell Death Dis

      Volume: 5 Issue: 7 Pages: e1341-e1341

    • DOI

      10.1038/cddis.2014.306

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dock3 overexpression and p38 MAPK inhibition synergistically stimulate neuroprotection and axon regeneration after optic nerve injury.2014

    • Author(s)
      Semba K, Namekata K, Kimura A, Harada C, Katome T, Yoshida H, Mitamura Y, Harada, T
    • Journal Title

      Neurosci Lett

      Volume: 581 Pages: 89-93

    • DOI

      10.1016/j.neulet.2014.08.034

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dock GEFs and their therapeutic potential: neuroprotection and axon regeneration.2014

    • Author(s)
      Namekata K, Kimura A, Kawamura K, Harada C, Harada T.
    • Journal Title

      Prog Retin Eye Res.

      Volume: 43 Pages: 1-16

    • DOI

      10.1016/j.preteyeres.2014.06.005

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma.2013

    • Author(s)
      Namekata K, Kimura A, Kawamura K, Guo X, Harada C, Tanaka K, Harada, T.
    • Journal Title

      Cell Death and Differentiation

      Volume: 20 Issue: 9 Pages: 1250-1256

    • DOI

      10.1038/cdd.2013.91

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dock3 interaction with a glutamate-receptor NR2D subunit protects neurons from excitotoxicity2013

    • Author(s)
      Ning Bai, Hideki Hayashi, Tomomi Aida, Kazuhiko Namekata, Takayuki Harada, Masayoshi Mishina and Kohichi Tanaka
    • Journal Title

      Molecular Brain

      Volume: 6 Issue: 1 Pages: 22-22

    • DOI

      10.1186/1756-6606-6-22

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury.2013

    • Author(s)
      Katome, T., Namekata, K., Guo, X., Semba, K., Kittaka, D., Kawamura, K., Kimura, A., Harada, C., Ichijo, H., Mitamura, Y. and Harada, T.
    • Journal Title

      Cell Death Differ.

      Volume: 20 Issue: 2 Pages: 270-280

    • DOI

      10.1038/cdd.2012.122

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] permidine stimulates neuroprotection and optic nerve regeneration following optic nerve injury.2015

    • Author(s)
      Takahiko Noro, Kazuhiko Namekata, Xiaoli Guo, Atsuko Kimura, Yuriko Azuchi, Tadashi Nakano, Hiroshi Tsuneoka, Takayuki Harada.
    • Organizer
      Asia-ARVO
    • Place of Presentation
      Pacifico Yokohama, Yokohama
    • Year and Date
      2015-02-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Valproic acid protects retinal neurons from NMDA-induced neurotoxicity via stimulation of neuronal TrkB receptors.2015

    • Author(s)
      Atsuko Kimura, Kazuhiko Namekata, Xiaoli Guo, Takahiko Noro, Chikako Harada, Takayuki Harada.
    • Organizer
      Asia-ARVO
    • Place of Presentation
      Pacifico Yokohama, Yokohama
    • Year and Date
      2015-02-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経変性疾患における神経保護・軸索再生の研究.2015

    • Author(s)
      行方和彦
    • Organizer
      第17回東邦大学理学部生物分子科学賞記念講演
    • Place of Presentation
      東邦大学 千葉県習志野市
    • Year and Date
      2015-01-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Dock8/10 regulate severity of inflammatory demyelination disorder.2014

    • Author(s)
      Kazuhiko Namekata, Xiaoli Guo, Atsuko Kimura, Chikako Harada, Takayuki Harada.
    • Organizer
      The ARVO (The Association for Research in Vision and Ophthalmology)
    • Place of Presentation
      U.S.A. Orlando
    • Year and Date
      2014-05-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Combined inhibition of angiotensin II type 1 receptor and ASK1 significantly attenuates autoimmune optic neuritis.2014

    • Author(s)
      Xiaoli Guo, Kazuhiko Namekata, Chikako Harada, Takayuki Harada.
    • Organizer
      The ARVO (The Association for Research in Vision and Ophthalmology)
    • Place of Presentation
      U.S.A. Orlando
    • Year and Date
      2014-05-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Dock3 protects retinal neurons in a mouse model of normal tension glaucoma.2014

    • Author(s)
      Kazuhiko Namekata, Xiaoli Guo, Chikako Harada, Takayuki Harada.
    • Organizer
      The 2014 World Ophthalmology Congress
    • Place of Presentation
      東京国際ファーラム 東京
    • Year and Date
      2014-04-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Inhibition of Angiotensin II Ameliorates Autoimmune Optic Neuritis by Suppressing Innate Immune Responses.2014

    • Author(s)
      Xiaoli Guo, Kazuhiko Namekata, Chikako Harada, Takayuki Harada.
    • Organizer
      The 2014 World Ophthalmology Congress
    • Place of Presentation
      東京国際ファーラム 東京
    • Year and Date
      2014-04-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Dock8 is a therapeutic target for CNS inflammation.

    • Author(s)
      Kazuhiko Namekata, Chikako Harada, Xiaoli Guo, Takayuki Harada.
    • Organizer
      43rd Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Interaction between renin-angiotensin and innate immune systems in autoimmune neuroinflammation.

    • Author(s)
      Xiaoli Guo, Kazuaki Nakamura, Chikako Harada, Kuniko Kohyama, Heather A. Behanna, D. Martin Watterson, Yoh Matsumoto, Takayuki Harada.
    • Organizer
      43rd Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Roles of ASK1 in neuroprotection and axonal regeneration after optic nerve injury.

    • Author(s)
      Daiji Kittaka, Kazuhiko Namekata, Takuji Kurimoto, Xiaoli Guo, Chikako Harada, Takayuki Harada.
    • Organizer
      43rd Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Dock3を活用した網膜・視神経再生研究

    • Author(s)
      行方和彦.
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] ASK1-p38経路の阻害は視神経外傷による神経細胞死を抑制する

    • Author(s)
      香留崇、仙波賢太郎、行方和彦、原田高幸、三田村佳典
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Book] Optic nerve regeneration. Neuroprotection and Neuroregeneration for Retinal Diseases.2014

    • Author(s)
      Kazuhiko Namekata, Takayuki Harada (Toru Nakazawa, Yasushi Kitaoka, Takayuki Harada, eds)
    • Total Pages
      356
    • Publisher
      Springer Japan
    • Related Report
      2014 Annual Research Report
  • [Remarks] 公益財団法人東京都医学総合研究所

    • URL

      http://www.igakuken.or.jp

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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