Prevention of injured neuron death by adennovirus vector.

为了探索神经再生过程的分子基础，我们利用差异显示-聚合酶链式反应(Differential Display-PCR)技术对舌下运动神经元损伤后表达上调的基因进行了鉴定，成功地分离出了可能与神经元存活和再生相关的新的和已知的分子。腺病毒介导的基因转移是挽救或修复受损神经元的一种有趣的手段。因此，我们尝试建立腺病毒介导的大鼠基因转移系统。在建立了损伤运动神经元的特异性基因转移系统后，我们利用我们的腺病毒系统揭示了两条信号通路(P13K介导的通路和ERK介导的生长因子受体下游通路)之间的明显功能差异。此外，我们还揭示了Akt在体外和体内对轴突延长的新活性。用腺病毒介导的基因转移系统也揭示了其他分子的功能意义。例如，一种新的Rho家族蛋白TC10被证明对轴突延长具有功能。本项目的研究结果为神经再生研究提供了有用的工具，为在实验动物身上检测某一分子的功能提供了有用的工具，也为临床上对脑创伤、脑缺血或神经退行性疾病如ALS、帕金森病等进行治疗干预开辟了可能性。

In an attempt to explore the molecular basis of nerve regeneration process, we have employed differential display-PCR to identify genes whose mRNA expression were up-regulated in injured hypoglossal motor neurons, and succeeded in isolating both novel as well as known molecules with possible association with neuronal survival and regeneration. To rescue or repair injured neurons, the adenovirus mediated gene transfer is one of intriguing means. We thus attempted to establish adenovirus mediated gene transfer system using rat. After establishing the gene transfer system specific to injured motor neurons, we have revealed distinct functional differences between two signaling pathways (P13K-mediated and ERK-mediated pathways downstream growth factor receptors) using our adenovirus system. In addition, we have also revealed a novel activity of Akt on neurite elongation both in vitro and in vivo. Functional significance of other molecules are also revealed by using this adenovirus mediated gene transfer system. For instance a novel Rho family protein TC10 was proved to have a function on neurite elongation. The results obtained in the present project provide useful tool for the nerve regeneration studies, in which the function of a certain molecule are examined in experimental animal, and also open up a possibility of therapeutic intervention in clinical conditions like brain trauma, ischaemia, or neurodegenerative conditions like ALS, Parkinson's disease, etc.