PMID- 20615870
OWN - NLM
STAT- MEDLINE
DCOM- 20101005
LR  - 20220309
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 285
IP  - 36
DP  - 2010 Sep 3
TI  - Mammalian target of rapamycin (mTOR) activation increases axonal growth capacity 
      of injured peripheral nerves.
PG  - 28034-43
LID - 10.1074/jbc.M110.125336 [doi]
AB  - 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.
FAU - Abe, Namiko
AU  - Abe N
AD  - Department of Anatomy and Neurobiology, Washington University in St. Louis, 
      School of Medicine, St. Louis, Missouri 63110, USA.
FAU - Borson, Steven H
AU  - Borson SH
FAU - Gambello, Michael J
AU  - Gambello MJ
FAU - Wang, Fan
AU  - Wang F
FAU - Cavalli, Valeria
AU  - Cavalli V
LA  - eng
GR  - R01 NS060709/NS/NINDS NIH HHS/United States
GR  - R01NS060709/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100708
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (GAP-43 Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Tsc2 protein, mouse)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Axons/*metabolism
MH  - Female
MH  - GAP-43 Protein/metabolism
MH  - Ganglia, Spinal/metabolism/pathology
MH  - Gene Deletion
MH  - Gene Expression Regulation
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Mice
MH  - *Peripheral Nerve Injuries
MH  - Peripheral Nerves/metabolism/*pathology/physiopathology
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Recovery of Function
MH  - Regeneration
MH  - TOR Serine-Threonine Kinases
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/deficiency/genetics/metabolism
PMC - PMC2934668
EDAT- 2010/07/10 06:00
MHDA- 2010/10/06 06:00
PMCR- 2011/09/03
CRDT- 2010/07/10 06:00
PHST- 2010/07/10 06:00 [entrez]
PHST- 2010/07/10 06:00 [pubmed]
PHST- 2010/10/06 06:00 [medline]
PHST- 2011/09/03 00:00 [pmc-release]
AID - S0021-9258(19)89132-9 [pii]
AID - M110.125336 [pii]
AID - 10.1074/jbc.M110.125336 [doi]
PST - ppublish
SO  - J Biol Chem. 2010 Sep 3;285(36):28034-43. doi: 10.1074/jbc.M110.125336. Epub 2010 
      Jul 8.