Dock family proteins in demyelination and neuroinflammation
Project/Area Number |
25640043
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Neurochemistry/Neuropharmacology
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Research Institution | Tokyo 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)
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Keywords | Dock3 / 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.
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Report
(3 results)
Research Products
(28 results)
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[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.
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Journal Title
Cell Death and Disease
Volume: 6
Pages: e1720
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
American Journal of Pathology
Volume: 185
Pages: 756-764
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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
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Journal Title
Neuroscience Letters
Volume: 592
Pages: 27-31
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
Neuroscience Letters
Volume: 588
Pages: 108-113
DOI
Related Report
Peer Reviewed
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[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. and Harada, T.
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Journal Title
Journal of Diabetes and its Complications
Volume: 29
Pages: 275-281
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
Cell Death and Disease
Volume: 6
Pages: e1963
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Dock3 protects myelin in the cuprizone model for demyelination.2014
Author(s)
Namekata, K., Kimura, A., Harada, C., Yoshida, H., Matsumoto, Y. and *Harada, T.
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Journal Title
Cell Death and Disease
Volume: 5
Pages: e1395
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[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. and *Harada, T.
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Journal Title
Cell Death and Disease
Volume: 5
Pages: e1341
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Renin-angiotensin system regulates neurodegeneration in a mouse model of normal tension glaucoma.2014
Author(s)
Semba, K., Namekata, K., Guo, X., Harada, C., *Harada T., Mitamura, Y.
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Journal Title
Cell Death and Disease
Volume: 5
Pages: e1333
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Dock3 overexpression and p38 MAPK inhibition synergistically stimulate neuroprotection and axon regeneration after optic nerve injury2014
Author(s)
Semba, K., Namekata, K., Kimura, A., Harada, C., Katome. T., Yoshida, H., Mitamura, Y. and *Harada, T.
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Journal Title
Neuroscience Letters
Volume: 581
Pages: 89-93
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
Cell Death and Differentiation
Volume: 20
Pages: 270-280
DOI
Related Report
Peer Reviewed
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