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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Smith, Patrice D. Kramvis, Ioannis Xu, Bengang He, Zhigang Park, Kevin Kyungsuk Wang, Chen Cai, Bin Connolly, Lauren Liu, Kai Hu, Yang Sahin, Mustafa |
| Description | Author Affiliation: Park KK ( F. M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.) |
| Abstract | 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. |
| ISSN | 00368075 |
| e-ISSN | 10959203 |
| Journal | Science |
| Issue Number | 5903 |
| Volume Number | 322 |
| Language | English |
| Publisher | American Association for the Advancement of Science (United States) |
| Publisher Date | 2008-11-07 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Axons Physiology Carrier Proteins Metabolism Nerve Regeneration PTEN Phosphohydrolase Phosphotransferases (Alcohol Group Acceptor) Signal Transduction Animals Axotomy Cell Survival Mice Mice, Knockout Nerve Crush Optic Nerve Genetics Protein Biosynthesis Retinal Ganglion Cells Ribosomal Protein S6 TOR Serine-Threonine Kinases Tumor Suppressor Proteins Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | History and Philosophy of Science |
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