ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Mammalian target of rapamycin's distinct roles and effectiveness in promoting compensatory axonal sprouting in the injured CNS.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 42 citations in OpenAlex.
- Natural Products and Neuroregeneration: Rethinking Discovery Beyond Bioavailability Through Pseudo-Natural Product Design.Biomedicines · 2026Review
- Therapeutic Intervention of Corticospinal Tract Sprouting after Unilateral Traumatic Brain Injury via METTL1-Mediated tRNA mMolecular neurobiology · 2025Article
- Molecular signaling predicts corticospinal axon growth state and muscle response plasticity induced by neuromodulation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Osteopontin enhances the effect of treadmill training and promotes functional recovery after spinal cord injury.Molecular biomedicine · 2023Article
- TargetingiScience · 2022Article
- Compounds co-targeting kinases in axon regulatory pathways promote regeneration and behavioral recovery after spinal cord injury in mice.Experimental neurology · 2022Article
- PI 3-kinase delta enhances axonal PIPEMBO molecular medicine · 2020Article
- Treatment with Mesenchymal-Derived Extracellular Vesicles Reduces Injury-Related Pathology in Pyramidal Neurons of Monkey Perilesional Ventral Premotor Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Advances in the Signaling Pathways Downstream of Glial-Scar Axon Growth Inhibitors.Frontiers in cellular neuroscience · 2020Review
- Targeting chondroitinase ABC to axons enhances the ability of chondroitinase to promote neurite outgrowth and sprouting.PloS one · 2020Article
- Neuronal activity and microglial activation support corticospinal tract and proprioceptive afferent sprouting in spinal circuits after a corticospinal system lesion.Experimental neurology · 2019Article
- Comparison of gene expression profile of the spinal cord of sprouting-capable neonatal and sprouting-incapable adult mice.BMC genomics · 2019Article
- Review
- Stimulation-dependent remodeling of the corticospinal tract requires reactivation of growth-promoting developmental signaling pathways.Experimental neurology · 2018Article
- Electroacupuncture Restores Locomotor Functions After Mouse Spinal Cord Injury in Correlation With Reduction of PTEN and p53 Expression.Frontiers in molecular neuroscience · 2018Article
- Microtopographical cues promote peripheral nerve regeneration via transient mTORC2 activation.Acta biomaterialia · 2017Article
- CSPGs inhibit axon branching by impairing mitochondria-dependent regulation of actin dynamics and axonal translation.Developmental neurobiology · 2017Article
- Combined chondroitinase and KLF7 expression reduce net retraction of sensory and CST axons from sites of spinal injury.Neurobiology of disease · 2017Article
- Resveratrol improves neuron protection and functional recovery through enhancement of autophagy after spinal cord injury in mice.American journal of translational research · 2017Article
- Optogenetic Interrogation of Functional Synapse Formation by Corticospinal Tract Axons in the Injured Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mammalian target of rapamycin (mTOR) functions as a master sensor of nutrients and energy, and controls protein translation and cell growth. Deletion of phosphatase and tensin homolog (PTEN) in adult CNS neurons promotes regeneration of injured axons in an mTOR-dependent manner. However, others have demonstrated mTOR-independent axon regeneration in different cell types, raising the question of how broadly mTOR regulates axonal regrowth across different systems. Here we define the role of mTOR in promoting collateral sprouting of spared axons, a key axonal remodeling mechanism by which functions are recovered after CNS injury. Using pharmacological inhibition, we demonstrate that mTOR is dispensable for the robust spontaneous sprouting of corticospinal tract axons seen after pyramidotomy in postnatal mice. In contrast, moderate spontaneous axonal sprouting and induced-sprouting seen under different conditions in young adult mice (i.e., PTEN deletion or degradation of chondroitin proteoglycans; CSPGs) are both reduced upon mTOR inhibition. In addition, to further determine the potency of mTOR in promoting sprouting responses, we coinactivate PTEN and CSPGs, and demonstrate that this combination leads to an additive increase in axonal sprouting compared with single treatments. Our findings reveal a developmental switch in mTOR dependency for inducing axonal sprouting, and indicate that PTEN deletion in adult neurons neither recapitulates the regrowth program of postnatal animals, nor is sufficient to completely overcome an inhibitory environment. Accordingly, exploiting mTOR levels by targeting PTEN combined with CSPG degradation represents a promising strategy to promote extensive axonal plasticity in adult mammals.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.