Optic nerve regeneration by overexpression of the microtubule regulator, SCG10 family

成年哺乳动物的中枢神经系统神经元在轴突损伤后几乎不能再生。在这项研究中，为了促进视网膜节细胞轴突再生，我们研究了强制表达控制微管的基因(MTS)的效果。作为这种MT控制蛋白的候选蛋白，我们选择了SCG10。以往的研究表明，SCG10家族通过去极化参与神经元胞质的形成，在神经元的可塑性和轴突再生中发挥重要作用。在此，我们首先构建了特异性表达SCG10的病毒载体，并将其感染体外培养的海马神经元。尽管该基因被成功地导入细胞，但通过SCG蛋白的过度表达来评估，神经元突起的长度和分支点的数量与对照未转基因神经元相比出人意料地减少。由此可见，SCG10单独对神经元突起的延伸有抑制作用。然后，我们对…进行扩展此外，她还试图观察SCG10的其他基因如MT控制蛋白、RB3、SCLIP和stathmin联合表达的效果。然而，我们没有成功地研究这些SCG10样蛋白的联合作用。此外，我们还试图从神经细胞凋亡受到抑制的Bcl-2过度表达的小鼠中分离出视网膜神经节细胞。同样，我们没有成功地分离出足够的视网膜神经节细胞来评估它们的存活率和轴突再生能力。2004年，我们通过比较全长Rb3和不带N端的截短Rb3的效果，研究了具有特定结构域的N-末端是否参与了SCG10‘S在MTS解聚中的作用。结果发现N-末端结构域对于控制MTS的聚合起着至关重要的作用。因此，SCG10家族一般可以利用N-末端结构域的控制区来控制MTS的动力学，并通过该区域来控制神经过程和神经形状。较少

CNS neurons of adult mammals hardly regenerate after axonal damage. In this study, in order to promote axonal regeneration of axotomized retinal ganglion cells, we examined the effect of compulsory expression of genes that control microtubules (MTs). As a candidate of such MT controlling protein we chose SCG10. From previous studies SCG10 family is know to be involved in neuronal cytoskelton formation through depolinezatoin of MTs and it plays an important role in neuronal plasticity and axonal regeneration. Here we first constructed a virus vector which specifically expresses SCG10 and infected it into the hippocampal neurons in vitro. Although the gene was successfully introduced into the cells, as assessed by an over-expression of SCG protein, the length of neuronal process and the number of branching points were, unexpectedly reduced as compared with control untransfected neurons. This, it appears that SCG10 alone has suppressing effect for neuronal process extension. Then, we furt … More her tried to see the effect of combined expressions of other genes of SCG10 like MT controlling proteins, RB3, SCLIP and Stathmin. However, we did not succeed to examine the combined effects of these SCG10 like proteins. Furthermore, we tried to isolate retinal ganglion cells from Bcl-2 over-exoressed mice where neuronal apoptosis is inhibited. Again we did not succeed to isolate retinal ganglion cells enough to evaluate their survivability and capacity for axonal regeneration.In 2004 we examined whether or no N-terminals with specific domains that contribute to the SCG10's function in depolymerization of MTs by comparing the effect of full-length RB3 with N-terminals and truncated RB3 without such N-terminals. As a result we found that the N-terminal domain is essentially important for control of polymerization of MTs. Thus the SCG10 family in general may control the dynamics of MTs using controlling region of the N-terminal domain and through which neural processes and neural shapes may be controlled. Less