权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

通过微管调节因子 SCG10 家族的过度表达实现视神经再生

基本信息

批准号：
13558096
负责人：
FUKUDA Yutaka
金额：
$ 8.96万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

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

成年哺乳动物中枢神经系统神经元轴突损伤后几乎不能再生。在这项研究中，为了促进轴突再生的轴突切断视网膜神经节细胞，我们检查了强制表达的基因控制微管（MT）的效果。作为这种MT控制蛋白的候选物，我们选择SCG 10。SCG 10家族通过MTs的去极化参与神经元胞浆的形成，在神经元的可塑性和轴突再生中发挥重要作用。本研究首先构建了特异性表达SCG 10的病毒载体，并将其感染到体外培养的海马神经元中。尽管通过SCG蛋白的过表达评估，基因被成功地引入细胞中，但与对照未转染的神经元相比，神经元突起的长度和分支点的数量出乎意料地减少。这表明单独的SCG 10对神经元突起延伸具有抑制作用。然后，我们 ...更多信息她试图观察SCG 10的其他基因如MT控制蛋白、RB 3、SCLIP和Stathmin的组合表达的效果。然而，我们没有成功地检查这些SCG 10样蛋白的组合作用。此外，我们试图从Bcl-2过度表达的小鼠中分离出视网膜神经节细胞，其中神经元凋亡被抑制。同样，我们没有成功地分离视网膜神经节细胞足以评估其生存能力和能力轴突regeneration.In 2004年，我们检查是否有N-末端的特定结构域，有助于SCG 10的功能，在解聚的MT比较全长RB 3与N-末端和截断RB 3没有这样的N-末端的效果。因此，我们发现，N-末端结构域是至关重要的控制聚合的MT。因此，SCG 10家族通常可以使用N-末端结构域的控制区域来控制MT的动力学，并且通过该控制区域可以控制神经过程和神经形状。少