Nogo-66抑制中枢神经轴突生长的机制尚未被完全阐明。申请者前期研究发现，钙离子升高和糖原合成酶激酶3β(GSK-3β)参与Nogo-66抑制轴突生长的机制；但几乎完全抑制GSK-3β只能部分解除Nogo-66的轴突抑制作用，提示存在其它激酶通路。已知轴突的生长依赖微管相关分子的作用，微管相关分子受多个激酶调控，微管亲和力调节蛋白2 （MARK2）具有调节微管相关蛋白的活性，调控轴突生长的作用；有预实验提示Nogo-66作用于神经元后MARK2磷酸化水平有改变。另多项依据表明，MARK2可能参与Nogo-66抑制轴突生长的机制。申请者拟从检测Nog-66抑制轴突生长后MARK2的活性改变、MARK2对微管相关分子活性的影响、以及MARK2对突起生长的影响等方面来证实MARK2参与Nogo-66抑制轴突生长的机制。该研究对于深度揭示Nogo-66抑制中枢神经元轴突生长的机制有重要意义。

The mechanism of Nogo-66 inhibiting axon outgrowth is not fully known. We previously found that increasing of Calcium and GSK-3β activation took part in Nogo-66 inhibiting axon outgrowth. Nervertheless, almost totally inhibiting GSK-3β activity only partly ameliorated the inhibition of neurite outgrowth induced by Nogo-66. This indicate another kinase pathway except for GSK-3β. It is known that axon elongation depends on action of microtube associated-proteins, which are regulated by lot of kinases. Microtubule affinity-regulating kinase 2 (MARK2) can regulate the activity of the microtubule-associated protein to further affect axon outgrowth. Our preliminary experiments showed changes of MARK2 acitvity after Nogo-66 added in N2a neurons. Moreover, a number of evidence indicates that MARK2 must be invloved in mechanism of Nogo-66 inhibiting axon outgrowth. To prove the fact that MARK2 is involved in the mechanism of Nogo-66 inhibiting axon outgrowth,we will analyze the change of MARK2 activity after Nogo-66 inhibiting axon growth and investigate the effect of MARK2 on activity of microtubule-associated molecules and axon outgrowth. This study will be important to exposit the mechanism of Nogo-66 inhibiting axon outgrowth.