Mammalian Target of Rapamycin (mTOR) Activation Increases Axonal Growth Capacity of Injured Peripheral Nerves

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 abilit...

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Veröffentlicht in:The Journal of biological chemistry 2010-09, Vol.285 (36), p.28034-28043
Hauptverfasser: Abe, Namiko, Borson, Steven H., Gambello, Michael J., Wang, Fan, Cavalli, Valeria
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container_end_page 28043
container_issue 36
container_start_page 28034
container_title The Journal of biological chemistry
container_volume 285
creator Abe, Namiko
Borson, Steven H.
Gambello, Michael J.
Wang, Fan
Cavalli, Valeria
description 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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subjects Animals
Axon
Axon Regeneration
Axons - metabolism
Developmental Biology
DRG Neuron
Female
Ganglia, Spinal - metabolism
Ganglia, Spinal - pathology
GAP-43 Protein - metabolism
Gap43
Gene Deletion
Gene Expression Regulation
Humans
Intracellular Signaling Peptides and Proteins - metabolism
Mice
mTOR
Neurobiology
Neurodevelopment
Peripheral Nerve Injuries
Peripheral Nerves - metabolism
Peripheral Nerves - pathology
Peripheral Nerves - physiopathology
Protein-Serine-Threonine Kinases - metabolism
Recovery of Function
Regeneration
TOR Complex (TORC)
TOR Serine-Threonine Kinases
Translation Regulation
TSC2
Tuberous Sclerosis Complex 2 Protein
Tumor Suppressor Proteins - deficiency
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
title Mammalian Target of Rapamycin (mTOR) Activation Increases Axonal Growth Capacity of Injured Peripheral Nerves
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