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

By Fang Sun, Kevin K. Park, Stephane Belin, Dongqing Wang, Tao Lu, Gang Chen, Kang Zhang, Cecil Yeung, G. Feng, B. Yankner and 1 more. Nature, 2011

725 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience

View Paper: https://www.semanticscholar.org/paper/1c4e6991150a9275b3ac8b193a5abf36e8df99a2

How researchers see this paper

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In Cellular and Molecular Neuroscience

1. G. Ferraro
2. L. Mckerracher
3. A. Fournier
4. E. Rosenzweig

In Developmental Neuroscience

1. G. Ferraro
2. L. Mckerracher
3. A. Fournier

Citations in the corpus

• Long-Distance Growth and Connectivity of Neural Stem Cells After Severe Spinal Cord Injury (2012, positive): “PTEN inhibits the activity of ‘‘mammalian target of rapamycin’’ (mTOR), and neuronal knockout of PTEN has been reported to enhance central axonal regeneration (Park et al., 2008; Liu et al., 2010; Sun et al., 2011).”
• Rho signaling and axon regeneration. (2012, background): “axon regeneration and if combinations may be synergistic, such as observed when PTEN and suppressor of cytokine signaling 3 are genetically deleted simultaneously (Sun et al., 2011).”