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Science 322 (5903): 963-966

Copyright © 2008 by the American Association for the Advancement of Science

Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway

Kevin Kyungsuk Park,* Kai Liu,* Yang Hu,* Patrice D. Smith,* Chen Wang, Bin Cai, Bengang Xu, Lauren Connolly, Ioannis Kramvis, Mustafa Sahin, Zhigang He{dagger}

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.

F. M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: zhigang.he{at}childrens.harvard.edu


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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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S. J. Henle, G. Wang, E. Liang, M. Wu, M.-m. Poo, and J. R. Henley (2011)
J. Neurosci. 31, 7016-7027
   Abstract »    Full Text »    PDF »
Regeneration of axons in injured spinal cord by activation of bone morphogenetic protein/Smad1 signaling pathway in adult neurons.
P. Parikh, Y. Hao, M. Hosseinkhani, S. B. Patil, G. W. Huntley, M. Tessier-Lavigne, and H. Zou (2011)
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   Abstract »    Full Text »    PDF »
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A. M. Winzeler, W. J. Mandemakers, M. Z. Sun, M. Stafford, C. T. Phillips, and B. A. Barres (2011)
J. Neurosci. 31, 6481-6492
   Abstract »    Full Text »    PDF »
In vivo imaging reveals a phase-specific role of STAT3 during central and peripheral nervous system axon regeneration.
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   Abstract »    Full Text »    PDF »
Engineering neuronal growth cones to promote axon regeneration over inhibitory molecules.
E.-M. Hur, I. H. Yang, D.-H. Kim, J. Byun, Saijilafu, W.-L. Xu, P. R. Nicovich, R. Cheong, A. Levchenko, N. Thakor, et al. (2011)
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   Abstract »    Full Text »    PDF »
Acid Fibroblast Growth Factor and Peripheral Nerve Grafts Regulate Th2 Cytokine Expression, Macrophage Activation, Polyamine Synthesis, and Neurotrophin Expression in Transected Rat Spinal Cords.
H.-S. Kuo, M.-J. Tsai, M.-C. Huang, C.-W. Chiu, C.-Y. Tsai, M.-J. Lee, W.-C. Huang, Y.-L. Lin, W.-C. Kuo, and H. Cheng (2011)
J. Neurosci. 31, 4137-4147
   Abstract »    Full Text »    PDF »
Taxol Facilitates Axon Regeneration in the Mature CNS.
V. Sengottuvel, M. Leibinger, M. Pfreimer, A. Andreadaki, and D. Fischer (2011)
J. Neurosci. 31, 2688-2699
   Abstract »    Full Text »    PDF »
Akt Suppresses Retrograde Degeneration of Dopaminergic Axons by Inhibition of Macroautophagy.
H.-C. Cheng, S. R. Kim, T. F. Oo, T. Kareva, O. Yarygina, M. Rzhetskaya, C. Wang, M. During, Z. Talloczy, K. Tanaka, et al. (2011)
J. Neurosci. 31, 2125-2135
   Abstract »    Full Text »    PDF »
Rapamycin Suppresses Mossy Fiber Sprouting But Not Seizure Frequency in a Mouse Model of Temporal Lobe Epilepsy.
P. S. Buckmaster and F. H. Lew (2011)
J. Neurosci. 31, 2337-2347
   Abstract »    Full Text »    PDF »
Emerging functions of myelin-associated proteins during development, neuronal plasticity, and neurodegeneration.
F. Llorens, V. Gil, and J. A. del Rio (2011)
FASEB J 25, 463-475
   Abstract »    Full Text »    PDF »
Multipotent Adult Progenitor Cells Prevent Macrophage-Mediated Axonal Dieback and Promote Regrowth after Spinal Cord Injury.
S. A. Busch, J. A. Hamilton, K. P. Horn, F. X. Cuascut, R. Cutrone, N. Lehman, R. J. Deans, A. E. Ting, R. W. Mays, and J. Silver (2011)
J. Neurosci. 31, 944-953
   Abstract »    Full Text »    PDF »
Dynamic Patterns of Histone Lysine Methylation in the Developing Retina.
R. C. Rao, K. T. Tchedre, M. T. A. Malik, N. Coleman, Y. Fang, V. E. Marquez, and D. F. Chen (2010)
Invest. Ophthalmol. Vis. Sci. 51, 6784-6792
   Abstract »    Full Text »    PDF »
Long-Distance Axon Regeneration in the Mature Optic Nerve: Contributions of Oncomodulin, cAMP, and pten Gene Deletion.
T. Kurimoto, Y. Yin, K. Omura, H.-y. Gilbert, D. Kim, L.-P. Cen, L. Moko, S. Kugler, and L. I. Benowitz (2010)
J. Neurosci. 30, 15654-15663
   Abstract »    Full Text »    PDF »
Ras Homolog Enriched in Brain (Rheb) Enhances Apoptotic Signaling.
S. Karassek, C. Berghaus, M. Schwarten, C. G. Goemans, N. Ohse, G. Kock, K. Jockers, S. Neumann, S. Gottfried, C. Herrmann, et al. (2010)
J. Biol. Chem. 285, 33979-33991
   Abstract »    Full Text »    PDF »
Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration.
C. Samara, C. B. Rohde, C. L. Gilleland, S. Norton, S. J. Haggarty, and M. F. Yanik (2010)
PNAS 107, 18342-18347
   Abstract »    Full Text »    PDF »
Targets for Neural Repair Therapies After Stroke.
S. T. Carmichael (2010)
Stroke 41, S124-S126
   Abstract »    Full Text »    PDF »
Oligodendrocyte-Myelin Glycoprotein and Nogo Negatively Regulate Activity-Dependent Synaptic Plasticity.
S. J. Raiker, H. Lee, K. T. Baldwin, Y. Duan, P. Shrager, and R. J. Giger (2010)
J. Neurosci. 30, 12432-12445
   Abstract »    Full Text »    PDF »
Mammalian Target of Rapamycin (mTOR) Activation Increases Axonal Growth Capacity of Injured Peripheral Nerves.
N. Abe, S. H. Borson, M. J. Gambello, F. Wang, and V. Cavalli (2010)
J. Biol. Chem. 285, 28034-28043
   Abstract »    Full Text »    PDF »
PTEN depletion rescues axonal growth defect and improves survival in SMN-deficient motor neurons.
K. Ning, C. Drepper, C. F. Valori, M. Ahsan, M. Wyles, A. Higginbottom, T. Herrmann, P. Shaw, M. Azzouz, and M. Sendtner (2010)
Hum. Mol. Genet. 19, 3159-3168
   Abstract »    Full Text »    PDF »
Signaling to Transcription Networks in the Neuronal Retrograde Injury Response.
I. Michaelevski, Y. Segal-Ruder, M. Rozenbaum, K. F. Medzihradszky, O. Shalem, G. Coppola, S. Horn-Saban, K. Ben-Yaakov, S. Y. Dagan, I. Rishal, et al. (2010)
Science Signaling 3, ra53
   Abstract »    Full Text »    PDF »
PTEN Inhibition to Facilitate Intrinsic Regenerative Outgrowth of Adult Peripheral Axons.
K. J. Christie, C. A. Webber, J. A. Martinez, B. Singh, and D. W. Zochodne (2010)
J. Neurosci. 30, 9306-9315
   Abstract »    Full Text »    PDF »
Topographically specific regeneration of sensory axons in the spinal cord.
P. Harvey, B. Gong, A. J. Rossomando, and E. Frank (2010)
PNAS 107, 11585-11590
   Abstract »    Full Text »    PDF »
Neuroproteomics Approaches to Decipher Neuronal Regeneration and Degeneration.
F. Sun and V. Cavalli (2010)
Mol. Cell. Proteomics 9, 963-975
   Abstract »    Full Text »    PDF »
A Chemical Screen Identifies Novel Compounds That Overcome Glial-Mediated Inhibition of Neuronal Regeneration.
L. C. Usher, A. Johnstone, A. Erturk, Y. Hu, D. Strikis, I. B. Wanner, S. Moorman, J. W. Lee, J. Min, H. H. Ha, et al. (2010)
J. Neurosci. 30, 4693-4706
   Abstract »    Full Text »    PDF »
Neurotrophic Effect of a Novel TrkB Agonist on Retinal Ganglion Cells.
Y. Hu, S. Cho, and J. L. Goldberg (2010)
Invest. Ophthalmol. Vis. Sci. 51, 1747-1754
   Abstract »    Full Text »    PDF »
A New Role for RPTP{sigma} in Spinal Cord Injury: Signaling Chondroitin Sulfate Proteoglycan Inhibition.
Y. Duan and R. J. Giger (2010)
Science Signaling 3, pe6
   Abstract »    Full Text »    PDF »
A Large-Scale Chemical Screen for Regulators of the Arginase 1 Promoter Identifies the Soy Isoflavone Daidzeinas a Clinically Approved Small Molecule That Can Promote Neuronal Protection or Regeneration via a cAMP-Independent Pathway.
T. C. Ma, A. Campana, P. S. Lange, H.-H. Lee, K. Banerjee, J. B. Bryson, L. Mahishi, S. Alam, R. J. Giger, S. Barnes, et al. (2010)
J. Neurosci. 30, 739-748
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-kinase signaling in the vertebrate retina.
R. V. S. Rajala (2010)
J. Lipid Res. 51, 4-22
   Abstract »    Full Text »    PDF »
Differential Gene Expression in the Developing Lateral Geniculate Nucleus and Medial Geniculate Nucleus Reveals Novel Roles for Zic4 and Foxp2 in Visual and Auditory Pathway Development.
S. Horng, G. Kreiman, C. Ellsworth, D. Page, M. Blank, K. Millen, and M. Sur (2009)
J. Neurosci. 29, 13672-13683
   Abstract »    Full Text »    PDF »
The Development of Developmental Neuroscience.
C. Mason (2009)
J. Neurosci. 29, 12735-12747
   Full Text »    PDF »
Nuclear Power for Axonal Growth.
M. C. Subang and P. M. Richardson (2009)
Science 326, 238-239
   Abstract »    Full Text »    PDF »
KLF Family Members Regulate Intrinsic Axon Regeneration Ability.
D. L. Moore, M. G. Blackmore, Y. Hu, K. H. Kaestner, J. L. Bixby, V. P. Lemmon, and J. L. Goldberg (2009)
Science 326, 298-301
   Abstract »    Full Text »    PDF »
Collaborative Models for Translational Neuroscience and Rehabilitation Research.
B. H. Dobkin (2009)
Neurorehabil Neural Repair 23, 633-640
   Abstract »    PDF »
Striking the balance between PTEN and PDK1: it all depends on the cell context.
A. Iwanami, T. F. Cloughesy, and P. S. Mischel (2009)
Genes & Dev. 23, 1699-1704
   Abstract »    Full Text »    PDF »
Axons find their way in the snow.
Y. Zou (2009)
Development 136, 2135-2139
   Abstract »    Full Text »    PDF »
Inhibition of the Mammalian Target of Rapamycin Signaling Pathway Suppresses Dentate Granule Cell Axon Sprouting in a Rodent Model of Temporal Lobe Epilepsy.
P. S. Buckmaster, E. A. Ingram, and X. Wen (2009)
J. Neurosci. 29, 8259-8269
   Abstract »    Full Text »    PDF »
Tuberous Sclerosis Complex Activity Is Required to Control Neuronal Stress Responses in an mTOR-Dependent Manner.
A. Di Nardo, I. Kramvis, N. Cho, A. Sadowski, L. Meikle, D. J. Kwiatkowski, and M. Sahin (2009)
J. Neurosci. 29, 5926-5937
   Abstract »    Full Text »    PDF »
Tuberous sclerosis complex, implication from a rare genetic disease to common cancer treatment.
K. Inoki and K.-L. Guan (2009)
Hum. Mol. Genet. 18, R94-R100
   Abstract »    Full Text »    PDF »
How are neurons wired to form functional and plastic circuits?: Meeting on Axon Guidance, Synaptogenesis & Neural Plasticity.
E. Stoeckli and Y. Zou (2009)
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