Evaluation of a drug-target-molecule for demyelinating disorders using Dock7 knockdown mouse
| Project/Area Number |
23650200
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
YAMAUCHI Junji 独立行政法人国立成育医療研究センター, 薬剤治療研究部, 室長 (20335483)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ミエリン形成 / 脱ミエリン現象 / 交換因子 / 低分子量GTP結合蛋白質 / 創薬標的分子 / 先天性疾患 / グリア細胞 / 人工組織構築 / ミエリン化 / 脱ミエリン化 / チロシンキナーゼ / セリン・スレオニンキナーゼ / 治療標的分子 / ノックダウンマウス / 末梢神経 / 脱随疾患 / 髄鞘化 / 遺伝子改変動物 / RNA干渉 / 分子標的治療 / シグナル伝達 / 神経細胞 / 共培養 / 組織形成 |
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| Research Abstract |
During development of the peripheral nervous system (PNS), Schwann cells (SCs) wrap axons to form a multilamellar structure called myelin, which functions as an insulator surrounding axons. In peripheral neuropathies such as Charcot-Marie-Tooth (CMT) disease, chronic demyelination and defective remyelination are repeated, causing more severe neuropathies. It is thus thought that development of a drug that promotes healthy myelination, with minimal side effects, may lead to useful therapeutic methods for these diseases. However, specific therapeutic drug targets that healthily promote myelination have hitherto remained unclear. In this study, we generated new transgenic mice expressing shRNA for Dock7, which knocked down Dock7 protein levels. We describe that knockdown of Dock7 specifically promotes myelination in vivo and in vitro. To the best of our knowledge, this is the first report of a possible therapeutic target molecule that promotes myelination without reduced axon thickness.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] n vivo expression of the Arf6 guanine-nucleotide exchange factor cytohesin-1 in mice exhibits enhanced myelin thickness in nerves.2013
Author(s)
Tomohiro Torii, Yuki Miyamoto, Naoko Onami, Hideki Tsumura, Noriko Nemoto, Katsumasa Kawahara, Minoru Kato, Jun Kotera, Kazuaki Nakamura, Akito Tanoue, and Junji Yamauchi
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Journal Title
Journal of Molecular Neuroscience
Volume: 51
Issue: 2
Pages: 522-531
DOI
Related Report
Peer Reviewed
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[Journal Article] The atypical guanine-nucleotide exchange factor, Dock7, negatively regulates Schwann cell differentiation and myelination.2011
Author(s)
Junji Yamauchi, Yuki Miyamoto, Hajime Hamasaki, Atsushi Sanbe, Shinji Kusakawa, Akane Nakamura, Hideki Tsumura, Masahiro Maeda, Noriko Nemoto, Katsumasa Kawahara, Tomohiro Torii, and Akito Tanoue
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Journal Title
J. Neurosci
Volume: 31
Issue: 35
Pages: 12579-12592
DOI
Related Report
Peer Reviewed
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