Nogo-66能够抑制中枢轴突的生长，其详细机制还未被阐明。申请者新近的研究结果表明，Nogo-66抑制轴突生长有PKB/Gsk-3β参与；另外还发现PKB/Gsk-3β下游的分子是MARK-2。 但是，调控Gsk-3β的上游信号分子尚不清楚。有研究表明，整合素连接激酶（ILK）可影响GSK-3β和MARK-2活性。预实验结果发现，Nogo-66作用于神经元后，ILK活性降低。本研究目的明确ILK是否为Nogo-66抑制轴突生长的信号通路的上游分子，设计从细胞和组织水平两方面研究：1）Nogo-66 抑制神经元突起生长中，ILK 活性变化；2）ILK对PKB/Gsk-3β和MARK-2激酶活性的调控作用；3）干预ILK 对Nogo-66 抑制突起生长的影响。本研究对深入了解髓鞘分子抑制轴突生长的机制，寻找阻断髓鞘分子抑制轴突生长的最佳通路节点提供理论依据，具有重要的科学意义。

The mechanism of Nogo-66 inhibiting axon outgrowth has not been fully understood until now. Our previous study suggested that PKB/GSK-3β activation took part in Nogo-66 inhibiting axon outgrowth. Furthermore, we recently found that MARK-2 was in the downstream of PKB/GSK-3β. However, the molecules that regulate Gsk-3β are still unclear. It is known that axon elongation depends on action of GSK-3β, which are activated by ILK. ILK can regulates the activity of the GSK-3β and MARK-2 to further affect axon outgrowth. The preliminary experiments showed changes of ILK activity after Nogo-66 added in N2a cells. Moreover, a number of evidence indicates that ILK must be invloved in mechanism of Nogo-66 inhibiting axon outgrowth. To prove the fact that ILK is involved in the mechanism of Nogo-66 inhibiting axon outgrowth, our project include in vivo and in vitro studies: 1) analyze the change of ILK activity after Nogo-66 inhibiting axon growth, 2) investigate the effect of ILK on activity of PKB/Gsk-3β and MARK-2, 3) the effect of ILK on axon outgrowth after inhibition by Nogo-66. This study is critical to explore the mechanism of Nogo-66 inhibiting axon outgrowth.