2013 Fiscal Year Final Research Report
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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| 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 |
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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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Research Products
(10 results)
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[Journal Article] The atypical guanine-nucleotide exchange factor, Dock7, negatively regulates Schwann cell differentiation and myelination2011
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
Pages: 12579-12592
DOI
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