Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway
| Autor: | Kai Liu, Kevin K. Park, Zhigang He, Lauren Connolly, Ioannis Kramvis, Mustafa Sahin, Bengang Xu, Patrice D. Smith, Chen Wang, Bin Cai, Yang Hu |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Retinal Ganglion Cells
Cell Survival Nerve Crush medicine.medical_treatment Biology Retinal ganglion Tuberous Sclerosis Complex 1 Protein Article Mice Conditional gene knockout medicine Animals PTEN Tensin Axon PI3K/AKT/mTOR pathway Mice Knockout Ribosomal Protein S6 Multidisciplinary TOR Serine-Threonine Kinases Tumor Suppressor Proteins Regeneration (biology) PTEN Phosphohydrolase Axotomy Optic Nerve Axons Nerve Regeneration Cell biology Phosphotransferases (Alcohol Group Acceptor) medicine.anatomical_structure Biochemistry Protein Biosynthesis biology.protein Carrier Proteins Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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