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

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

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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

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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.

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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

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

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