PTEN Deletion Enhances the Regenerative Ability of Adult Corticospinal Neurons
By Kai-Fenp Liu, Yi Lu, Jae K. Lee, Ramsey F. Samara, Rafer Willenberg, Ilse Sears-Kraxberger, Andrea Tedeschi, Kevin K. Park, Duo Jin, B. Cai and 5 more. Nature Neuroscience, 2010
966 citations recorded by the source corpus.
Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. We found that PTEN/mTOR are critical for controlling the regenerative capacity of mouse corticospinal neurons. After development, the regrowth potential of CST axons was lost and this was accompanied by a downregulation of mTOR activity in corticospinal neurons. Axonal injury further diminished neuronal mTOR activity in these neurons. Forced upregulation of mTOR activity in corticospinal neurons by conditional deletion of Pten, a negative regulator of mTOR, enhanced compensatory sprouting of uninjured CST axons and enabled successful regeneration of a cohort of injured CST axons past a spinal cord lesion. Furthermore, these regenerating CST axons possessed the ability to reform synapses in spinal segments distal to the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.
Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/5e213954a16a907172fd5fa46a6aa0c25e1b4772
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In Cellular and Molecular Neuroscience
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).”