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Cited by 754Nerve injury and regenerationNeurogenesis and neuroplasticity mechanismsAxon Guidance and Neuronal Signaling

Sustained axon regeneration induced by co-deletion of PTEN and SOCS3

Open access
Sun, Fang, Park, Kevin K., Belin, Stephane, Wang, Dongqing, Lu, Tao, Chen, Gang, Zhang, Kang, Yeung, Cecil +3 more·2011·Nature
DOI 10.1038/nature10594PMC PMC3240702
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Abstract

A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either phosphatase and tensin homologue (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signalling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around 2 weeks after the crush injury. Here we show that, remarkably, simultaneous deletion of both PTEN and SOCS3 enables robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only results in the induction of many growth-related genes, but also allows RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as key for sustaining long-distance axon regeneration in adult CNS, a crucial step towards functional recovery.

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  • PTEN and SOCS3 inhibition induce axonal sprouting in multiple adult CNS systems, including optic nerve and spinal cord injury.

    “PTEN and SOCS3 inhibition induce axonal sprouting in multiple adult CNS systems, including optic nerve and spinal cord injury8,35.”

    From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [35]

    The paper reports that deleting PTEN and SOCS3 in adult retinal ganglion cells promotes axon regeneration after optic nerve injury (Abstract; no page given). It does not report PTEN/SOCS3-induced sprouting after spinal cord injury or demonstrate the effect across multiple adult CNS systems. Spinal cord injury appears only in references to other work. (LLM, conf=0.88)

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Cites

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Research works printed but not linked: 28

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Cited by

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Authors
Sun, F., Park, K. K., Belin, S., Wang, D., Lu, T., Chen, G., Zhang, K., Yeung, C., Feng, G., Yankner, B. A., & He, Z.
Affiliations
  • Harvard University (US)
  • University of Miami (US)
  • McGovern Institute for Brain Research (US)
  • University of California San Diego (US)
Corresponding author
He, Zhigang
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2011-11-06
Volume
480
Issue
7377
Pages
372-375
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature10594
PMC
PMC3240702
OpenAlex
W2105989397
Cited by
754
References
2
Citations by year
2026: 33 · 2025: 49 · 2024: 49 · 2023: 46 · 2022: 49 · 2021: 52 · 2020: 62 · 2019: 55 · 2018: 51 · 2017: 43 · 2016: 60 · 2015: 57 · 2014: 50 · 2013: 52 · 2012: 44
FWCI
19.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (DP1AG044161)
  • National Eye Institute (R01EY021342, R01EY018660, R01EY021526, R01EY021374)
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, SOCS3, nerve crush injury, optic nerve regeneration, retinal ganglion cells, mTOR signaling, JAK/STAT signaling, STAT3, growth-related gene expression, central nervous system repair
MeSH terms
Suppressor of Cytokine Signaling 3 Protein, Animals, Axons, Gene Expression Regulation, Mice, Inbred C57BL, Nerve Crush, Nerve Regeneration, Optic Nerve, Retinal Ganglion Cells, Signal Transduction, Optic Nerve Injuries, Cell Growth Processes, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins, PTEN Phosphohydrolase, Mice

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