Effects of the modulation of the innate immunity and Dock family member on multiple sclerosis

• Project/Area Number: 25430082
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: GUO Xiaoli 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, 主任研究員 (50443114)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: グリア細胞 / 多発性硬化症 / 視神経炎 / EAE / 細胞種特異的な遺伝子欠損マウス / ブリモニジン / 自然免疫 / candesartan

Outline of Final Research Achievements

We examined the effects of ASK1, one of the stress response genes, on the severity of the clinical score and optic neuritis in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Clinical signs of EAE were mild in glia-specific ASK1 conditional knockout mice. We also examined the effect of Dock8, an atypical guanine nucleotide exchange factor, on EAE, and found that optic neuritis was mild in Dock8 deficient mice.

Research Products

• [Journal Article] TrkB signaling in retinal glia stimulates neuroprotection after optic nerve injury. (2015)
  • Author(s): Harada, C., Azuchi, Y., Noro, T., Guo, X., Kimura, A., Namekata, K., Harada, T.
  • Journal Title: American Journal of Pathology Volume: 185 Issue: 12 Pages: 3238-3247
  • DOI: 10.1016/j.ajpath.2015.08.005
  • Peer Reviewed / Acknowledgement Compliant
• [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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Spermidine ameliorates neurodegeneration in a mouse model of normal tension glaucoma. (2015)
  • Author(s): Noro, T., Namekata, K., Azuchi, Y., Kimura, A., Guo, X., Harada, C., Nakano, T., Tsuneoka, H., Harada, T.
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 56 Issue: 8 Pages: 5012-5019
  • DOI: 10.1167/iovs.15-17142
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Valproic acid prevents NMDA-induced retinal ganglion cell death via stimulation of neuronal TrkB receptor signaling (2015)
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Valproic acid prevents retinal degeneration in a murine model of normal tension glaucoma (2015)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Brimonidine suppresses loss of retinal neurons and visual function in a murine model of optic neuritis (2015)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Renin-angiotensin system regulates neurodegeneration in a mouse model of normal tension glaucoma (2015)
  • 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
  • Peer Reviewed / Open Access / 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
  • 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
  • Peer Reviewed
• [Presentation] Neuroprotection by valproic acid and spermidine in a mouse model of normal tension glaucoma (2015)
  • Author(s): Takayuki Harada, Atsuko Kimura, Takahiko Noro, Xiaoli Guo, Kazuhiko Namekata, Chikako Harada
  • Organizer: 45th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-10-20
  • Int'l Joint Research
• [Presentation] Brimonidine suppresses loss of retinal neurons and visual function in murine models of glaucoma and optic neuritis (2015)
  • Author(s): Xiaoli Guo, Kazuhiko Namekata, Atsuko Kimura, Takahiko Noro, Chikako Harada, Takayuki Harada
  • Organizer: 45th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-10-19
  • Int'l Joint Research
• [Presentation] Brimonidine protects retinal neurons and visual function in a murine model of optic neuritis (2015)
  • Author(s): Guo X., Namekata K., Kimura A., Noro T., Harada C., Harada T
  • Organizer: 第119回 日本眼科学会総会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
  • Year and Date: 2015-04-17
• [Presentation] Brimonidine protects retinal neurons and visual function in a murine model of optic neuritis (2015)
  • Author(s): Xiaoli Guo
  • Organizer: 第119回 日本眼科学会総会
  • Place of Presentation: ロイトン札幌、札幌
  • Year and Date: 2015-04-17
• [Presentation] Dock3はERKシグナルを介して視神経の脱髄を抑制する (2015)
  • Author(s): 行方和彦、郭暁麗
  • Organizer: 第119回 日本眼科学会総会
  • Place of Presentation: ロイトン札幌、札幌
  • Year and Date: 2015-04-17
• [Presentation] Dock3はERKシグナルを介して視神経の脱髄を抑制する (2015)
  • Author(s): 行方和彦、木村敦子、郭 曉麗、原田知加子、原田高幸
  • Organizer: 第119回 日本眼科学会総会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
  • Year and Date: 2015-04-16
• [Presentation] Spermidine stimulates neuroprotection and optic nerve regeneration following optic nerve injury (2015)
  • Author(s): Takahiko Noro, Xiaoli Guo
  • Organizer: 2015 Asia-ARVO (The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Pacifico Yokohama, Yokohama
  • Year and Date: 2015-02-18
• [Presentation] Valproic acid protects retinal neurons from NMDA-induced neurotoxicity via stimulation of neuronal TrkB receptors (2015)
  • Author(s): Atsuko Kimura, Xiaoli Guo
  • Organizer: 2015 Asia-ARVO (The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Pacifico Yokohama, Yokohama
  • Year and Date: 2015-02-18
• [Presentation] Dock8/10 regulate severity of inflammatory demyelination disorder (2014)
  • Author(s): Kazuhiko Namekata, Xiaoli Guo
  • Organizer: The ARVO (The Association for Research in Vision and Ophthalmology) 2014 Annual Meeting
  • Place of Presentation: Orlando, USA
  • Year and Date: 2014-05-08
• [Presentation] Combined inhibition of angiotensin II type 1 receptor and ASK1 significantly attenuates autoimmune optic neuritis (2014)
  • Author(s): Xiaoli Guo
  • Organizer: The ARVO (The Association for Research in Vision and Ophthalmology) 2014 Annual Meeting
  • Place of Presentation: Orlando, USA
  • Year and Date: 2014-05-08
• [Presentation] Inhibition of angiotensin II ameliorates autoimmune optic neuritis by suppressing innate immune responses (2014)
  • Author(s): Xiaoli Guo
  • Organizer: World Ophthalmology Congress of the International Council of Ophthalmology (WOC) 2014
  • Place of Presentation: Tokyo International Forum / Imperial Hotel, Tokyo
  • Year and Date: 2014-04-05
• [Presentation] Dock3 protects retinal neurons in a mouse model of normal tension glaucoma (2014)
  • Author(s): Kazuhiko Namekata, Xiaoli Guo
  • Organizer: World Ophthalmology Congress of the International Council of Ophthalmology (WOC) 2014
  • Place of Presentation: Tokyo International Forum / Imperial Hotel, Tokyo
  • Year and Date: 2014-04-03
• [Presentation] Interaction between renin-angiotensin and innate immune systems in autoimmune neuroinflammation
  • Author(s): Guo X
  • Organizer: 43rd Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego、アメリカ
• [Presentation] Dock8 is a therapeutic target for CNS inflammation
  • Author(s): Namekata K
  • Organizer: 43rd Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego、アメリカ
• [Presentation] Roles of ASK1 in neuroprotection and axonal regeneration after optic nerve injury
  • Author(s): Kittaka D
  • Organizer: 43rd Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego、アメリカ
• [Book] Neuroprotection and Neuroregeneration for Retinal Diseases (2014)
  • Author(s): Xiaoli Guo
  • Total Pages: 356
  • Publisher: Springer Japan
• [Book] Neuroprotection and Neuroregeneration for Retinal Diseases (2014)
  • Author(s): Guo X
  • Total Pages: 505
  • Publisher: Springer Japan
• [Remarks] 視覚病態プロジェクト
• [Remarks] 視覚病態プロジェクトホームページ
• [Patent(Industrial Property Rights)] 視神経保護剤 (2015)
  • Inventor(s): 原田高幸、行方和彦、郭 暁麗 他
  • Industrial Property Rights Holder: 公益財団法人東京都医学総合研究所
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-04-30