Sustained axon regeneration induced by co-deletion of PTEN and SOCS3.
Sustained axon regeneration induced by co-deletion of PTEN and SOCS3.
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DOI：
10.1038/nature10594
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发表时间：
2011-11-06
期刊：
影响因子：
64.8
通讯作者：
He, Zhigang
中科院分区：
文献类型：
--
作者：
Sun, Fang;Park, Kevin K.;Belin, Stephane;Wang, Dongqing;Lu, Tao;Chen, Gang;Zhang, Kang;Yeung, Cecil;Feng, Guoping;Yankner, Bruce A.;He, Zhigang
成人中枢神经系统（CNS）神经修复的一个巨大挑战是再生轴突为了与其目标重新连接通常需要行进很长的距离。因此，轴突再生的持续能力对于实现功能恢复至关重要。尽管缺失了磷酸酶和张力蛋白同源物（PTEN）（哺乳动物雷帕霉素靶蛋白（mTOR）的负调节物）或细胞因子信号传导抑制因子3（SOCS 3）（Janus激酶/信号转导和转录激活因子的负调节物），（JAK/STAT）途径，在成年视网膜神经节细胞（RGC）单独促进显着的视神经再生，这种再生在挤压伤后大约两周逐渐减少。值得注意的是，我们现在发现，同时删除PTEN和SOCS 3能够实现强大和持续的轴突再生。我们进一步表明，PTEN和SOCS 3调节两个独立的途径，协同作用，以促进增强轴突再生。基因表达分析表明，双缺失不仅导致许多生长相关基因的诱导，而且还允许RGCs在损伤后维持一系列基因在生理水平上的表达。我们的研究结果揭示了mTOR和STAT 3通路的同时激活是维持成年CNS长距离轴突再生的关键，这是功能恢复的关键一步。
A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either Phosphatase and tensin homolog (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signaling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around two weeks after the crush injury. Remarkably, we now find that simultaneous deletion of both PTEN and SOCS3 enables robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only results in the induction of many growth-related genes, but also allows RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as a key for sustaining long-distance axon regeneration in adult CNS, a crucial step toward functional recovery.
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影响因子：
16
作者：
Sengupta S;Peterson TR;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
5.3
作者：
Miao, Tizong;Wu, Dongsheng;Richardson, Peter M.
通讯作者：
Richardson, Peter M.
影响因子：
16.2
作者：
Smith, Patrice D.;Sun, Fang;Park, Kevin Kyungsuk;Cai, Bin;Wang, Chen;Kuwako, Kenichiro;Martinez-Carrasco, Irene;Connolly, Lauren;He, Zhigang
通讯作者：
He, Zhigang
影响因子：
5.3
作者：
Christie, Kimberly J.;Webber, Christine A.;Zochodne, Douglas W.
通讯作者：
Zochodne, Douglas W.
DOI：
10.1073/pnas.1015239108
发表时间：
2011-04-12
影响因子：
11.1
作者：
Bareyre, Florence M.;Garzorz, Natalie;Kerschensteiner, Martin
通讯作者：
Kerschensteiner, Martin