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

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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