| Mammalian target of rapamycin (mTOR) activation increases axonal growth capacity of injured peripheral nerves. | |
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MedLine Citation:
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PMID: 20615870 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Unlike neurons in the central nervous system (CNS), injured neurons in the peripheral nervous system (PNS) can regenerate their axons and reinnervate their targets. However, functional recovery in the PNS often remains suboptimal, especially in cases of severe damage. The lack of regenerative ability of CNS neurons has been linked to down-regulation of the mTOR (mammalian target of rapamycin) pathway. We report here that PNS dorsal root ganglial neurons (DRGs) activate mTOR following damage and that this activity enhances axonal growth capacity. Furthermore, genetic up-regulation of mTOR activity by deletion of tuberous sclerosis complex 2 (TSC2) in DRGs is sufficient to enhance axonal growth capacity in vitro and in vivo. We further show that mTOR activity is linked to the expression of GAP-43, a crucial component of axonal outgrowth. However, although TSC2 deletion in DRGs facilitates axonal regrowth, it leads to defects in target innervation. Thus, whereas manipulation of mTOR activity could provide new strategies to stimulate nerve regeneration in the PNS, fine control of mTOR activity is required for proper target innervation. |
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Authors:
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Namiko Abe; Steven H Borson; Michael J Gambello; Fan Wang; Valeria Cavalli |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-08 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-30 Completed Date: 2010-10-05 Revised Date: 2011-09-13 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 28034-43 Citation Subset: IM |
Affiliation:
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Department of Anatomy and Neurobiology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri 63110, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Axons / metabolism* Female GAP-43 Protein / metabolism Ganglia, Spinal / metabolism, pathology Gene Deletion Gene Expression Regulation Humans Intracellular Signaling Peptides and Proteins / metabolism* Mice Peripheral Nerves / injuries*, metabolism, pathology*, physiopathology Protein-Serine-Threonine Kinases / metabolism* Recovery of Function Regeneration TOR Serine-Threonine Kinases Tumor Suppressor Proteins / deficiency, genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 NS060709-04/NS/NINDS NIH HHS; R01NS060709/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/GAP-43 Protein; 0/Intracellular Signaling Peptides and Proteins; 0/Tumor Suppressor Proteins; 169027-60-5/tuberous sclerosis complex 2 protein; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
| Comments/Corrections | |
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