Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway

被引：1281

作者：

Park, Kevin Kyungsuk ^{[1
,2
]}

Liu, Kai ^{[1
,2
]}

Hu, Yang ^{[1
,2
]}

Smith, Patrice D. ^{[1
,2
]}

Wang, Chen ^{[1
,2
]}

Cai, Bin ^{[1
,2
]}

Xu, Bengang ^{[1
,2
]}

Connolly, Lauren ^{[1
,2
]}

Kramvis, Ioannis ^{[1
,2
]}

Sahin, Mustafa ^{[1
,2
]}

He, Zhigang ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA

来源：

SCIENCE | 2008年 / 322卷 / 5903期

关键词：

D O I：

10.1126/science.1161566

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The failure of axons to regenerate is a major obstacle for functional recovery after central nervous system (CNS) injury. Removing extracellular inhibitory molecules results in limited axon regeneration in vivo. To test for the role of intrinsic impediments to axon regrowth, we analyzed cell growth control genes using a virus- assisted in vivo conditional knockout approach. Deletion of PTEN ( phosphatase and tensin homolog), a negative regulator of the mammalian target of rapamycin ( mTOR) pathway, in adult retinal ganglion cells ( RGCs) promotes robust axon regeneration after optic nerve injury. In wild- type adult mice, the mTOR activity was suppressed and new protein synthesis was impaired in axotomized RGCs, which may contribute to the regeneration failure. Reactivating this pathway by conditional knockout of tuberous sclerosis complex 1, another negative regulator of the mTOR pathway, also leads to axon regeneration. Thus, our results suggest the manipulation of intrinsic growth control pathways as a therapeutic approach to promote axon regeneration after CNS injury.

引用

页码：963 / 966

页数：4

共 27 条

[1] Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation [J].