由PTEN和SOCS3的共同删除引起的持续的轴突再生
Fang Sun1, Kevin K Park, Stephane Belin
1F.M. Kirby Neurobiology Center, Children's Hospital, Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nature
|November 8, 2011
概括
在成年视网膜质细胞中同时删除PTEN和SOCS3促进了持续的轴突再生. 这种双重抑制激活了mTOR和STAT3通路,这对于中枢神经系统中长距离神经修复至关重要.
科学领域:
- 神经科学是一个神经科学.
- 再生医学是一种再生医学.
- 分子生物学分子生物学
背景情况:
- 成年人中枢神经系统 (CNS) 中的轴突再生受到长距离的限制,需要持续的生长能力.
- 在视网膜质细胞 (RGCs) 中,单个删除酸酶和张素同类物 (PTEN) 或细胞因子信号传递3 (SOCS3) 抑制剂可促进最初的视神经再生,但再生不能持续.
- PTEN 负调节了哺乳动物目标的拉巴胺素 (mTOR) 途径,而 SOCS3 负调节了 Janus 激酶/信号转换器和转录激活器 (JAK/STAT) 途径.
研究的目的:
- 研究同时删除PTEN和SOCS3对成年RGC中持续的轴突再生的协同效应.
- 阐明涉及促进中枢神经系统受伤后长距离轴突再生的分子途径.
主要方法:
- 在成年视网膜质细胞 (RGCs) 中进行基因操纵,以删除PTEN和SOCS3.
- 视神经压伤损伤模型来评估轴突再生.
- 基因表达分析以确定删除和损伤后的分子变化.
主要成果:
- 在成年RGC中同时删除PTEN和SOCS3使得轴突再生能够强大且持续,克服了在单个删除中观察到的逐渐缩小.
- 发现PTEN和SOCS3可以调节独立的通路,这些通路协同作用,增强轴突再生.
- 在双删除模型中,基因表达分析揭示了与生长相关的基因的诱导和在受伤后在RGC中维持生理基因表达水平.
- 同时激活mTOR和STAT3通路被确定为维持长距离轴突再生的关键.
结论:
- 对PTEN和SOCS3的双抑制是促进成人中枢神经系统中持续的轴突再生的有效策略.
- 通过联合PTEN和SOCS3删除来激活mTOR和STAT3通路的协同作用是克服再生障碍的关键.
- 这一发现是实现中枢神经系统损伤后功能恢复的重要一步.
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