演題詳細
Oral
グリア
Glia
開催日 | 2014/9/11 |
---|---|
時間 | 15:00 - 16:00 |
会場 | Room J(313+314) |
Chairperson(s) | 小泉 修一 / Schuichi Koizumi (山梨大学大学院医学工学総合研究部薬理学講座 / Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan) 津田 誠 / Makoto Tsuda (九州大学大学院薬学研究院ライフイノベーション分野 / Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Japan) |
ミエリン形成が強く促進されるArf6活性化因子の遺伝子改変マウス
In vivo expression of the Arf6 guanine-nucleotide exchange factor cytohesin-1 in mice exhibits enhanced myelin thickness in nerves
- O1-J-4-1
- 鳥居 知宏 / Tomohiro Torii:1 宮本 幸 / Yuki Miyamoto:1 田上 昭人 / Akito Tanoue:1 山内 淳司 / Junji Yamauchi:1,2
- 1:国立成育医療研究センター研究所・薬剤治療研究部 / NICHD, Tokyo, Japan 2:東京医科歯科大学大学院・医歯学総合研究科 / TMDU, Tokyo, Japan
The myelin sheath consists of a unique multiple-layer structure that acts as an insulator between neuronal axons to enhance the propagation of the action potential. In neuropathies such as demyelinating or dismyelinating diseases, chronic demyelination and defective remyelination occur repeatedly, leading to more severe neuropathy. As yet, little is known about the possibility of drug-target-specific medicine for such diseases. In the developing peripheral nervous system (PNS), myelin sheaths form as Schwann cells wrap individual axons. It is thought that the development of a drug promoting myelination by Schwann cells would provide effective therapy against peripheral nerve disorders: to test such treatment, genetically-modified mice overexpressing the drug target molecules are needed. We previously identified an Arf6 activator, the guanine-nucleotide exchange factor (GEF) cytohesin-1, as the signaling molecule controlling myelination of peripheral axons by Schwann cells; yet the important issue of whether cytohesin-1 itself promotes myelin thickness in vivo has remained unclear. Herein, we show that, in mouse PNS nerves, Schwann cell-specific expression of wild type cytohesin-1 exhibits enhanced myelin thickness. Downstream activation of Arf6 is also seen in these transgenic mice, revealing the involvement of the cytohesin-1 and Arf6 signaling unit in promoting myelination. These results suggest that cytohesin-1 may be a candidate for the basis of a therapy for peripheral neuropathies through its enhancement of myelin thickness.