Cited by 1,686Nerve injury and regenerationNeurogenesis and neuroplasticity mechanismsAxon Guidance and Neuronal Signaling

The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.

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

Open access

Park, Kevin Kyungsuk, Liu, Kai, Hu, Yang, Smith, Patrice D., Wang, Chen, Cai, Bin, Xu, Bengang, Connolly, Lauren, Kramvis, Ioannis, Sahin, Mustafa, He, Zhigang·2008·Science

DOI 10.1126/science.1161566PMC PMC2652400

Open this paper in CoChat — free account

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1126/science.1161566

Cites

27 of 27 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
Defining the role of mTOR in cancer
Guertin, D. A., & Sabatini, D. M. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.05.008 · Cited by 2,833
The Biology of Cancer
Weinberg, R. A., & Weinberg, R. A. (2006) · W.W. Norton eBooks · doi:10.1201/9780203852569 · Cited by 1,806
Glial inhibition of CNS axon regeneration
Yiu, G. C., & He, Z. (2006) · Nature reviews. Neuroscience · doi:10.1038/nrn1956 · Cited by 1,525
Self-citation
Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex
Brugarolas, J., Lei, K., Hurley, R. L., Manning, B. D., Reiling, J. H., Hafen, E., Witters, L. A., Ellisen, L. W., & Kaelin, W. G. (2004) · Genes & Development · doi:10.1101/gad.1256804 · Cited by 1,384
Targeting the PI3K-Akt pathway in human cancer
Luo, J., Manning, B. D., & Cantley, L. C. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00248-4 · Cited by 1,290
Degeneration and regeneration of axons in the lesioned spinal cord
Schwab, M. E., & Bartholdi, D. (1996) · Physiological Reviews · doi:10.1152/physrev.1996.76.2.319 · Cited by 1,124
Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, Control mTOR Signaling by Acting as a GTPase-Activating Protein Complex toward Rheb
Tee, A. R., Manning, B. D., Roux, P. P., Cantley, L. C., & Blenis, J. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00506-2 · Cited by 1,080
Insulin Activation of Rheb, a Mediator of mTOR/S6K/4E-BP Signaling, Is Inhibited by TSC1 and 2
Garami, A., Zwartkruis, F. J. T., Nobukuni, T., Joaquin, M., Roccio, M., Stocker, H., Kozma, S. C., Hafen, E., Bos, J. L., & Thomas, G. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00220-x · Cited by 1,043
CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure
Fitch, M. T., & Silver, J. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2007.05.014 · Cited by 1,007

Show all 27 references

Sorted by citations

Items 401–500 of 1,001

Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase
Chen, L., Chuang, M., Koorman, T., Boxem, M., Jin, Y., & Chisholm, A. D. (2015) · eLife · doi:10.7554/elife.08695 · Cited by 49
TIMP3 Attenuates the Loss of Neural Stem Cells, Mature Neurons and Neurocognitive Dysfunction in Traumatic Brain Injury
Gibb, S. L., Zhao, Y., Potter, D. R., Hylin, M. J., Bruhn, R. L., Baimukanova, G., Zhao, J., Xue, H., Abdel‐Mohsen, M., Pillai, S. K., et al. (2015) · Stem Cells · doi:10.1002/stem.2189 · Cited by 51
Adult neural precursors isolated from post mortem brain yield mostly neurons: An erythropoietin-dependent process
Marfia, G., Madaschi, L., Marra, F., Menarini, M., Bottai, D., Formenti, A., Bellardita, C., Giulio, A. M. D., Carelli, S., & Gorio, A. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.02.004 · Cited by 52
Asymmetric PI(3,4,5)P 3 and Akt Signaling Mediates Chemotaxis of Axonal Growth Cones
Henle, S. J., Wang, G. X., Liang, E. T., Wu, M., Poo, M.-M., & Henley, J. R. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0216-11.2011 · Cited by 57
The age factor in axonal repair after spinal cord injury: A focus on neuron-intrinsic mechanisms
Geoffroy, C. G., Meves, J. M., & Zheng, B. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.11.003 · Cited by 50
3D Visualization of Individual Regenerating Retinal Ganglion Cell Axons Reveals Surprisingly Complex Growth Paths
Bray, E. R., Noga, M., Thakor, K., Wang, Y., Lemmon, V., Park, K. K., & Tsoulfas, P. (2017) · eNeuro · doi:10.1523/eneuro.0093-17.2017 · Cited by 52
Self-citation
Astrocyte remodeling without gliosis precedes optic nerve axonopathy
Cooper, M., Collyer, J. W., & Calkins, D. J. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0542-0 · Cited by 52
The stem cell marker Prom1 promotes axon regeneration by down-regulating cholesterol synthesis via Smad signaling
Lee, J., Shin, J. E., Lee, B., Kim, H., Jeon, Y., Ahn, S. H., Chi, S. W., & Cho, Y. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920829117 · Cited by 51
AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury
Kong, G., Zhou, L., Serger, E., Palmisano, I., Virgiliis, F. D., Hutson, T. H., McLachlan, E., Freiwald, A., Montanara, P. L., Shkura, K., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0252-3 · Cited by 54
Long-term in vivo imaging of mouse spinal cord through an optically cleared intervertebral window
Wu, W., He, S., Wu, J., Chen, C., Li, X., Liu, K., & Qu, J. Y. (2022) · Nature Communications · doi:10.1038/s41467-022-29496-x · Cited by 55
Self-citation
A small molecule M1 promotes optic nerve regeneration to restore target-specific neural activity and visual function
Au, N. P. B., Raza, C., Kumar, G., Asthana, P., Tam, W. Y., Tang, K.-M., Ko, C., & Ma, C. H. E. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2121273119 · Cited by 53
PTEN Depletion Decreases Disease Severity and Modestly Prolongs Survival in a Mouse Model of Spinal Muscular Atrophy
Little, D., Valori, C. F., Mutsaers, C. A., Bennett, E., Wyles, M., Sharrack, B., Shaw, P. J., Gillingwater, T. H., Azzouz, M., & Ning, K. (2014) · Molecular Therapy · doi:10.1038/mt.2014.209 · Cited by 51
Neuronal Nogo-A upregulation does not contribute to ER stress-associated apoptosis but participates in the regenerative response in the axotomized adult retina
Pernet, V., Joly, S., Dalkara, D., Schwarz, O., Christ, F., Schaffer, D. V., Flannery, J. G., & Schwab, M. E. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.191 · Cited by 51
Ras Homolog Enriched in Brain (Rheb) Enhances Apoptotic Signaling*
Karassek, S., Berghaus, C., Schwarten, M., Goemans, C. G., Ohse, N., Kock, G., Jockers, K. F. G., Neumann, S., Gottfried, S., Herrmann, C., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.095968 · Cited by 54
Negative impact of rAAV2 mediated expression of SOCS3 on the regeneration of adult retinal ganglion cell axons
Hellström, M., Muhling, J., Ehlert, E., Verhaagen, J., Pollett, M. A., Hu, Y., & Harvey, A. R. (2010) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2010.12.003 · Cited by 51
Self-citation
RhoA knockdown by cationic amphiphilic copolymer/siRhoA polyplexes enhances axonal regeneration in rat spinal cord injury model
Gwak, S., Macks, C. P., Jeong, D. U., Kindy, M. S., Lynn, M., Webb, K., & Lee, J. S. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.01.003 · Cited by 51
Treatment with Mesenchymal-Derived Extracellular Vesicles Reduces Injury-Related Pathology in Pyramidal Neurons of Monkey Perilesional Ventral Premotor Cortex
Medalla, M., Chang, W., Calderazzo, S. M., Go, V., Tsolias, A., Goodliffe, J. W., Pathak, D., de Alba, D., Pessina, M. A., Rosene, D. L., et al. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2226-19.2020 · Cited by 51
Retinal Ganglion Cell Axon Regeneration Requires Complement and Myeloid Cell Activity within the Optic Nerve
Peterson, S. L., Li, Y., Sun, C., Wong, K. A., Leung, K. S., de Lima, S., Hanovice, N. J., Yuki, K., Stevens, B., & Benowitz, L. I. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0555-21.2021 · Cited by 51
Generation of a Transplantable Population of Human iPSC-Derived Retinal Ganglion Cells
Rabesandratana, O., Chaffiol, A., Mialot, A., Slembrouck-Brec, A., Joffrois, C., Nanteau, C., Rodrigues, A., Gagliardi, G., Reichman, S., Sahel, J., et al. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.585675 · Cited by 49
Up‐regulation of miR‐26a promotes neurite outgrowth and ameliorates apoptosis by inhibiting PTEN in bupivacaine injured mouse dorsal root ganglia
Cui, C., Gong, X., Qiu, J., & Fan, X. (2015) · Cell Biology International · doi:10.1002/cbin.10461 · Cited by 50
cJun promotes CNS axon growth
Lerch, J. K., Martinez‐Ondaro, Y., Bixby, J. L., & Lemmon, V. (2014) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2014.02.002 · Cited by 50
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
Horng, S. H., Kreiman, G., Ellsworth, C., Page, D. T., Blank, M. C., Millen, K. J., & Sur, M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2127-09.2009 · Cited by 48
Isoform Diversity and Regulation in Peripheral and Central Neurons Revealed through RNA-Seq
Lerch, J. K., Kuo, F., Motti, D., Morris, R., Bixby, J. L., & Lemmon, V. P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030417 · Cited by 50
ASPP1/2 Regulate p53-Dependent Death of Retinal Ganglion Cells through PUMA and Fas/CD95 ActivationIn Vivo
Wilson, A. M., Morquette, B., Abdouh, M., Unsain, N., Barker, P. A., Feinstein, E., Bernier, G., & Polo, A. D. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2635-12.2013 · Cited by 50
Expanded genetic screening in Caenorhabditis elegans identifies new regulators and an inhibitory role for NAD+ in axon regeneration
Kim, K. W., Tang, N. H., Piggott, C. A., Andrusiak, M. G., Park, S., Zhu, M., Kurup, N. S., Cherra, S. J., Wu, Z., Chisholm, A. D., et al. (2018) · eLife · doi:10.7554/elife.39756 · Cited by 50
Human retinal ganglion cell axon regeneration by recapitulating developmental mechanisms: effects of recruitment of the mTOR pathway
Teotia, P., Hook, M. J. V., Fischer, D., & Ahmad, I. (2019) · Development · doi:10.1242/dev.178012 · Cited by 52
Updates and challenges of axon regeneration in the mammalian central nervous system
Qian, C., & Zhou, F. (2020) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjaa026 · Cited by 50
Protective effects of intravitreal administration of mesenchymal stem cell-derived exosomes in an experimental model of optic nerve injury
Cui, Y., Liu, C.-Y., Huang, L., Chen, J., & Xu, N. (2021) · Experimental Cell Research · doi:10.1016/j.yexcr.2021.112792 · Cited by 52
Neuroplasticity of spinal cord injury and repair
Martin, J. H. (2022) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819410-2.00017-5 · Cited by 54
The PTEN inhibitor bisperoxovanadium enhances myelination by amplifying IGF‐1 signaling in rat and human oligodendrocyte progenitors
Paula, M. L. D., Cui, Q., Hossain, S., Antel, J. P., & Almazán, G. (2013) · Glia · doi:10.1002/glia.22584 · Cited by 51
Roles of channels and receptors in the growth cone during PNS axonal regeneration
Shim, S., & Ming, G. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.10.001 · Cited by 48
Glaucoma and optic nerve repair
Diekmann, H., & Fischer, D. (2013) · Cell and Tissue Research · doi:10.1007/s00441-013-1596-8 · Cited by 50
Strategies to Promote Long-Distance Optic Nerve Regeneration
Yang, S.-G., Li, C.-P., Peng, X.-Q., Teng, Z., Liu, C.-M., & Zhou, F. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00119 · Cited by 49
MicroRNAs 21 and 199a-3p Regulate Axon Growth Potential through Modulation of Pten and mTo r mRNAs
Kar, A. N., Lee, S. J., Sahoo, P. K., Thames, E. L., Yoo, S., Houlé, J. D., & Twiss, J. L. (2021) · eNeuro · doi:10.1523/eneuro.0155-21.2021 · Cited by 49
Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair
Saraswathy, V. M., Zhou, L., & Mokalled, M. H. (2024) · Nature Communications · doi:10.1038/s41467-024-50628-y · Cited by 50
PTEN inhibition prevents rat cortical neuron injury after hypoxia–ischemia
Zhao, J., Qu, Y., Wu, J., Cao, M., Ferriero, D. M., Zhang, L., & Mu, D. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.02.046 · Cited by 48
Gene therapy approaches to enhancing plasticity and regeneration after spinal cord injury
Franz, S., Weidner, N., & Blesch, A. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.01.015 · Cited by 48
An update on PTEN modulators – a patent review
Boosani, C. S., Gunasekar, P., & Agrawal, D. K. (2019) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2019.1669562 · Cited by 46
Pten coordinates retinal neurogenesis by regulating Notch signalling
Jo, H. S., Kang, K. H., Joe, C. O., & Kim, J. W. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.443 · Cited by 48
Dock GEFs and their therapeutic potential: Neuroprotection and axon regeneration
Namekata, K., Kimura, A., Kawamura, K., Harada, C., & Harada, T. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.06.005 · Cited by 57
Combinatorial Therapy Stimulates Long-Distance Regeneration, Target Reinnervation, and Partial Recovery of Vision After Optic Nerve Injury in Mice
de Lima, S., Habboub, G., & Benowitz, L. I. (2012) · International review of neurobiology · doi:10.1016/b978-0-12-407178-0.00007-7 · Cited by 47
Activating transcription factor 3 (ATF3) expression in the neural retina and optic nerve of zebrafish during optic nerve regeneration
Saul, K. E., Koke, J. R., & Garcia, D. (2009) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2009.10.042 · Cited by 47
Axon regeneration in C. elegans: Worming our way to mechanisms of axon regeneration
Byrne, A. B., & Hammarlund, M. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.08.015 · Cited by 46
Multitasking: Dual Leucine Zipper–Bearing Kinases in Neuronal Development and Stress Management
Jin, Y., & Zheng, B. (2019) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062644 · Cited by 45
Novel therapeutic targets for epilepsy intervention
Kambli, L., Bhatt, L. K., Oza, M. J., & Prabhavalkar, K. S. (2017) · Seizure · doi:10.1016/j.seizure.2017.07.014 · Cited by 47
Effects of rapamycin and TOR on aging and memory: implications for Alzheimer’s disease
Santos, R. X., Correia, S. C., Cardoso, S., Carvalho, C., Santos, M. S., & Moreira, P. I. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07262.x · Cited by 45
Regulation of Intrinsic Axon Growth Ability at Retinal Ganglion Cell Growth Cones
Steketee, M. B., Oboudiyat, C., Daneman, R., Trakhtenberg, E. F., Lamoureux, P., Weinstein, J. E., Heidemann, S. R., Barres, B. A., & Goldberg, J. L. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-13882 · Cited by 47
Differing Semaphorin 3A Concentrations Trigger Distinct Signaling Mechanisms in Growth Cone Collapse
Manns, R. P. C., Cook, G. M. W., Holt, C. E., & Keynes, R. J. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5964-11.2012 · Cited by 46
Caenorhabditis elegans: A new model organism for studies of axon regeneration
Ghosh-Roy, A., & Chisholm, A. D. (2010) · Developmental Dynamics · doi:10.1002/dvdy.22253 · Cited by 48
p110α of PI3K is necessary and sufficient for quiescence exit in adult muscle satellite cells
Wang, G., Zhu, H., Situ, C., Han, L., Yu, Y., Cheung, T. H., Liu, K., & Wu, Z. (2018) · The EMBO Journal · doi:10.15252/embj.201798239 · Cited by 49
Self-citation
Functional Electrical Stimulation and the Modulation of the Axon Regeneration Program
Jara, J. S., Agger, S., & Hollis, E. R., II (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00736 · Cited by 48
Downregulation of MicroRNA-193b-3p Promotes Autophagy and Cell Survival by Targeting TSC1/mTOR Signaling in NSC-34 Cells
Li, C., Chen, Y., Chen, X., Wei, Q., Cao, B., & Shang, H. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00160 · Cited by 45
“Genetic and pharmacological evidence has shown that deletion of TSC1, a negative regulator of mTOR signaling, led to constitutive activation of mTOR, neuroprotective effects and potently enhanced axon regeneration (Park et al., 2008).”
Background
Harnessing Astrocytes and Müller Glial Cells in the Retina for Survival and Regeneration of Retinal Ganglion Cells
Yoo, H.-S., Shanmugalingam, U., & Smith, P. D. (2021) · Cells · doi:10.3390/cells10061339 · Cited by 48
Self-citation
Subtype-specific survival and regeneration of retinal ganglion cells in response to injury
Tapia, M. L., Nascimento‐dos‐Santos, G., & Park, K. K. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.956279 · Cited by 44
Self-citation
Mesenchymal Stem Cell-Derived Exosomes in Ophthalmology: A Comprehensive Review
Wu, K. Y., Ahmad, H., Lin, G., Carbonneau, M., & Tran, S. D. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041167 · Cited by 51
Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants
Chen, M., Pekosz, A. S., Villano, J., Shen, W., Zhou, R., Kulaga, H. M., Li, Z., Smith, A. K., Gurung, A., Beck, S. E., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci174439 · Cited by 52
ATP-mediated protein kinase B Akt/mammalian target of rapamycin mTOR/p70 ribosomal S6 protein p70S6 kinase signaling pathway activation promotes improvement of locomotor function after spinal cord injury in rats
Hu, L., Sun, Z. G., Wen, Y., Cheng, G., Wang, S., Zhao, H. B., & Zhang, X. R. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.05.046 · Cited by 45
Differential response of C57BL/6J mouse and DBA/2J mouse to optic nerve crush
Templeton, J. P., Nassr, M. A., Vázquez-Chona, F., Freeman-Anderson, N. E., Orr, W. E., Williams, R. W., & Geisert, E. E. (2009) · BMC Neuroscience · doi:10.1186/1471-2202-10-90 · Cited by 45
PTEN/PI3K and MAPK signaling in protection and pathology following CNS injuries
Walker, C. L., Liu, N., & Xu, X. (2013) · Frontiers in Biology · doi:10.1007/s11515-013-1255-1 · Cited by 48
PTEN deletion enhances survival, neurite outgrowth and function of dopamine neuron grafts to MitoPark mice
Zhang, Y., Granholm, A.-C., Huh, K. H., Shan, L., Dı́az-Ruiz, O., Malik, N., Olson, L., Hoffer, B. J., Lupica, C. R., Hoffman, A. F., et al. (2012) · Brain · doi:10.1093/brain/aws196 · Cited by 45
Targets for Neural Repair Therapies After Stroke
Carmichael, S. T. (2010) · Stroke · doi:10.1161/strokeaha.110.597146 · Cited by 45
Intra‐axonal protein synthesis in development and beyond
Batista, A. F. R., & Hengst, U. (2016) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2016.03.004 · Cited by 45
The challenges of long-distance axon regeneration in the injured CNS
Chew, D. J., Fawcett, J. W., & Andrews, M. R. (2012) · Progress in brain research · doi:10.1016/b978-0-444-59544-7.00013-5 · Cited by 43
Following Spinal Cord Injury Transected Reticulospinal Tract Axons Develop New Collateral Inputs to Spinal Interneurons in Parallel with Locomotor Recovery
May, Z., Fenrich, K. K., Dahlby, J. S., Batty, N. J., Espin, A. T., & Fouad, K. (2017) · Neural Plasticity · doi:10.1155/2017/1932875 · Cited by 46
Bisperoxovanadium Mediates Neuronal Protection through Inhibition of PTEN and Activation of PI3K/AKT-mTOR Signaling after Traumatic Spinal Injuries
Walker, C. L., Wu, X., Liu, N., & Xu, X. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.6294 · Cited by 46
GSK3-CRMP2 signaling mediates axonal regeneration induced by Pten knockout
Leibinger, M., Hilla, A. M., Andreadaki, A., & Fischer, D. (2019) · Communications Biology · doi:10.1038/s42003-019-0524-1 · Cited by 45
Cellular reprogramming for successful CNS axon regeneration is driven by a temporally changing cast of transcription factors
Dhara, S. P., Rau, A., Flister, M. J., Recka, N. M., Laiosa, M. D., Auer, P. L., & Udvadia, A. J. (2019) · Scientific Reports · doi:10.1038/s41598-019-50485-6 · Cited by 43
MicroRNA-23a-3p improves traumatic brain injury through modulating the neurological apoptosis and inflammation response in mice
Li, Z., Xu, R., Zhu, X., Li, Y., Wang, Y., & Xu, W. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1691763 · Cited by 46
Dynamic Patterns of Histone Lysine Methylation in the Developing Retina
Rao, R. C., Tchedre, K. T., Malik, M. T., Coleman, N. L., Fang, Y., Márquez, V. E., & Chen, D. F. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-4730 · Cited by 46
Disruption of E3 ligase NEDD4 in peripheral neurons interrupts axon outgrowth: Linkage to PTEN
Christie, K. J., Martinez, J. A., & Zochodne, D. W. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.04.006 · Cited by 45
Animal Models of Retinal Injury
Blanch, R. J., Ahmed, Z., Berry, M., Scott, R. A. H., & Logan, A. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-8564 · Cited by 44
Cell-Type Specific Roles for PTEN in Establishing a Functional Retinal Architecture
Cantrup, R., Dixit, R., Palmesino, E., Bonfield, S. P., Shaker, T., Tachibana, N., Zinyk, D. L., Dalesman, S., Yamakawa, K., Stell, W. K., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032795 · Cited by 44
Mammalian Target of Rapamycin's Distinct Roles and Effectiveness in Promoting Compensatory Axonal Sprouting in the Injured CNS
Lee, D.-H., Luo, X., Yungher, B. J., Bray, E. R., Lee, J. K., & Park, K. K. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1935-14.2014 · Cited by 44
Self-citation
Genetic dissection of axon regeneration
Wang, Z., & Jin, Y. (2010) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.08.010 · Cited by 44
Transforming growth factor β-induced expression of chondroitin sulfate proteoglycans is mediated through non-Smad signaling pathways
Jahan, N., & Hannila, S. S. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.10.023 · Cited by 44
Neurotrophic Factors and the Regeneration of Adult Retinal Ganglion Cell Axons
Harvey, A. R., Ooi, J. W. W., & Rodger, J. (2012) · International review of neurobiology · doi:10.1016/b978-0-12-407178-0.00002-8 · Cited by 44
HDAC5 promotes optic nerve regeneration by activating the mTOR pathway
Pita‐Thomas, W., Mahar, M., Joshi, A., Gan, D., & Cavalli, V. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.03.011 · Cited by 44
AFF-1 fusogen can rejuvenate the regenerative potential of adult dendritic trees via self-fusion
Kravtsov, V., Oren‐Suissa, M., & Podbilewicz, B. (2017) · Development · doi:10.1242/dev.150037 · Cited by 44
EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment
Eva, R., Koseki, H., Kanamarlapudi, V., & Fawcett, J. W. (2017) · Journal of Cell Science · doi:10.1242/jcs.207423 · Cited by 44
Inhibition of GCK-IV kinases dissociates cell death and axon regeneration in CNS neurons
Patel, A. K., Broyer, R. M., Lee, C. D., Lu, T., Louie, M., Torre, A. L., Al‐Ali, H., Vu, M. T., Mitchell, K. L., Wahlin, K. J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2004683117 · Cited by 45
Self-citation
Damage-induced neuronal endopeptidase (DINE) enhances axonal regeneration potential of retinal ganglion cells after optic nerve injury
Kaneko, A., Kiryu‐Seo, S., Matsumoto, S., & Kiyama, H. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.212 · Cited by 45
Retrograde Signaling in the Optic Nerve Is Necessary for Electrical Responsiveness of Retinal Ganglion Cells
Chou, T.-H., Park, K. K., Luo, X., & Porciatti, V. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-11188 · Cited by 44
Self-citation
Redox Regulation of PTEN by Reactive Oxygen Species: Its Role in Physiological Processes
Trinh, V. H., Huu, T. N., Sah, D. K., Choi, J. M., Yoon, H.-J., Park, S. C., Jung, Y. S., & Lee, S.-R. (2024) · Antioxidants · doi:10.3390/antiox13020199 · Cited by 44
Targeted Repair of Spinal Cord Injury Based on miRNA‐124‐3p–Loaded Mesoporous Silica Camouflaged by Stem Cell Membrane Modified with Rabies Virus Glycoprotein
Fan, X., Shi, L., Yang, Z., Li, Y., Zhang, C., Bai, B., Lu, C., Yilihamu, E. E.-Y., Qi, Z., Li, W., et al. (2024) · Advanced Science · doi:10.1002/advs.202309305 · Cited by 43
μ‐Opioid Receptor Attenuates Aβ Oligomers‐Induced Neurotoxicity Through mTOR Signaling
Wang, Y., Wang, Y., Liu, T., Law, P., Loh, H. H., Qiu, Y. L., & Chen, H. (2014) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12316 · Cited by 43
Topographically specific regeneration of sensory axons in the spinal cord
Harvey, P. A., Gong, B., Rossomando, A. J., & Frank, E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003287107 · Cited by 43
AMIGO3 Is an NgR1/p75 Co-Receptor Signalling Axon Growth Inhibition in the Acute Phase of Adult Central Nervous System Injury
Ahmed, Z., Douglas, M. R., John, G., Berry, M., & Logan, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061878 · Cited by 43
Heterogeneous Nuclear Ribonucleoprotein K, an RNA-Binding Protein, Is Required for Optic Axon Regeneration inXenopus laevis
Liu, Y., Yu, H., Deaton, S. K., & Szaro, B. G. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5197-11.2012 · Cited by 43
The nuclear events guiding successful nerve regeneration
Kiryu‐Seo, S., & Kiyama, H. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00053 · Cited by 43
Inhibiting poly(ADP-ribosylation) improves axon regeneration
Byrne, A. B., McWhirter, R. D., Sekine, Y., Strittmatter, S. M., Miller, D. M., & Hammarlund, M. (2016) · eLife · doi:10.7554/elife.12734 · Cited by 44
Akt/mammalian target of rapamycin signaling pathway regulates neurite outgrowth in cerebellar granule neurons stimulated by methylcobalamin
Okada, K., Tanaka, H., Temporin, K., OKAMOTO, M. T., Kuroda, Y., Moritomo, H., Murase, T., & Yoshikawa, H. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.03.065 · Cited by 42
Axonal regeneration after spinal cord injury in zebrafish and mammals: differences, similarities, translation
Vajn, K., Plunkett, J. A., Tapanes-Castillo, A., & Oudega, M. (2013) · Neuroscience Bulletin · doi:10.1007/s12264-013-1361-8 · Cited by 43
Regulating Set-β's Subcellular Localization Toggles Its Function between Inhibiting and Promoting Axon Growth and Regeneration
Trakhtenberg, E. F., Wang, Y., Morkin, M. I., Fernandez, S. G., Mlacker, G. M., Shechter, J. M., Liu, X., Patel, K. H., Lapins, A., Yang, S., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3658-13.2014 · Cited by 42
MASH1/Ascl1a Leads to GAP43 Expression and Axon Regeneration in the Adult CNS
Williams, R. R., Venkatesh, I., Pearse, D. D., Udvadia, A. J., & Bunge, M. B. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118918 · Cited by 42
Neural Regeneration in Caenorhabditis elegans
Bejjani, R. M. E., & Hammarlund, M. (2012) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155550 · Cited by 44
Low-Intensity Pulsed Ultrasound Protects Retinal Ganglion Cell From Optic Nerve Injury Induced Apoptosis via Yes Associated Protein
Zhou, J., Liu, Y.-J., Chen, X., Zhang, X., Xu, J., Yang, K., Wang, D., Lin, S., & Ye, J. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00160 · Cited by 43
The Virtuous Cycle of Axon Growth: Axonal Transport of Growth‐Promoting Machinery as an Intrinsic Determinant of Axon Regeneration
Petrova, V., & Eva, R. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22608 · Cited by 42
Coordination of Necessary and Permissive Signals by PTEN Inhibition for CNS Axon Regeneration
Zhang, J., Yang, D., Huang, H., Sun, Y., & Hu, Y. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00558 · Cited by 41
Self-citation
Telomerase Reverse Transcriptase and p53 Regulate Mammalian Peripheral Nervous System and CNS Axon Regeneration Downstream of c-Myc
Ma, J., Ju, X., Xu, R., Wang, W.-H., Luo, Z., Liu, C., Yang, L., Li, B., Chen, J., Meng, B., et al. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.0419-19.2019 · Cited by 42
An Emerging Role of m6A in Memory: A Case for Translational Priming
Leonetti, A. M., Chu, M. Y., Ramnaraign, F. O., Holm, S., & Walters, B. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207447 · Cited by 42

Authors: Park, K. K., Liu, K., Hu, Y., Smith, P. D., Wang, C., Cai, B., Xu, B., Connolly, L., Kramvis, I., Sahin, M., & He, Z.
Affiliations: Harvard University (US)
F. M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Corresponding author: Park, Kevin Kyungsuk
Liu, Kai
Hu, Yang
Smith, Patrice D.
He, Zhigang
ORCID: Park, Kevin Kyungsuk
Liu, Kai
Hu, Yang
Smith, Patrice D.
Wang, Chen
Cai, Bin
Kramvis, Ioannis
He, Zhigang
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2008-11-07
Volume: 322
Issue: 5903
Pages: 963-966
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1161566
PMC: PMC2652400
OpenAlex: W2004538934
Cited by: 1,686
References: 27
Citations by year: 2026: 80 · 2025: 93 · 2024: 92 · 2023: 119 · 2022: 116 · 2021: 99 · 2020: 126 · 2019: 112 · 2018: 112 · 2017: 94 · 2016: 104 · 2015: 85 · 2014: 104 · 2013: 79 · 2012: 97
FWCI: 24.80
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS058956, R01NS051788)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Keywords: axon regeneration, PTEN, mTOR signaling, tuberous sclerosis complex 1, retinal ganglion cells, optic nerve injury, central nervous system injury, conditional knockout, protein synthesis
MeSH terms: Tuberous Sclerosis Complex 1 Protein, Animals, Axons, Carrier Proteins, Cell Survival, Nerve Crush, Nerve Regeneration, Optic Nerve, Retinal Ganglion Cells, Protein Biosynthesis, Signal Transduction, Phosphotransferases (Alcohol Group Acceptor), Mice, Knockout, Axotomy, Tumor Suppressor Proteins, Ribosomal Protein S6, PTEN Phosphohydrolase, Mice, TOR Serine-Threonine Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks