ArticleeLife2016
mTORC1 is necessary but mTORC2 and GSK3β are inhibitory for AKT3-induced axon regeneration in the central nervous system.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
84 citing papers in PubMed, 118 citations in OpenAlex.
- Ultrasound-responsive nanotherapy promotes axonal regeneration after SCI via reactivating CREB/miR-129-5p signaling.Bioactive materials · 2027Article
- Natural Products and Neuroregeneration: Rethinking Discovery Beyond Bioavailability Through Pseudo-Natural Product Design.Biomedicines · 2026Review
- Article
- Actin depolymerization promotes axon regeneration by restoring axonal mitochondrial transport in mouse models of optic neuropathy.Science translational medicine · 2026Article
- From Regeneration Failure to Functional Restoration: Unlocking the Neuronal-Intrinsic Regenerative Capacity as a Therapeutic Frontier for Optic Neuropathy and Glaucoma.CNS neuroscience & therapeutics · 2026Review
- Transcription factor activator protein 4 (AP4)-mediated intrinsic control of axon regeneration.Science advances · 2025Article
- SG06, a Chalcone Derivative Targets PI3K/AKT1 Pathway for Neuroprotection and Cognitive Enhancement in an Alzheimer's Disease-Like Zebrafish Model.Molecular neurobiology · 2025Article
- Plasmalogens Activate AKT/mTOR Signaling to Attenuate Reactive Oxygen Species Production in Spinal Cord Injury.Current gene therapy · 2025Article
- Marcks overexpression in retinal ganglion cells promotes optic nerve regeneration.Cell death & disease · 2024Article
- Immunomodulation by the combination of statin and matrix-bound nanovesicle enhances optic nerve regeneration.NPJ Regenerative medicine · 2024Article
- Lipin1 depletion coordinates neuronal signaling pathways to promote motor and sensory axon regeneration after spinal cord injury.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Natural compounds from herbs and nutraceuticals as glycogen synthase kinase-3β inhibitors in Alzheimer's disease treatment.CNS neuroscience & therapeutics · 2024Review
- Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Glycogen synthase kinase 3 signaling in neural regeneration in vivo.Journal of molecular cell biology · 2024Review
- Integrating Network Pharmacology, Transcriptomics to Reveal Neuroprotective of Curcumin Activate PI3K / AKT Pathway in Parkinson's Disease.Drug design, development and therapy · 2024Article
- Article
- Phosphorylated S6K1 and 4E-BP1 play different roles in constitutively active Rheb-mediated retinal ganglion cell survival and axon regeneration after optic nerve injury.Neural regeneration research · 2023Article
- RGC-specific ATF4 and/or CHOP deletion rescues glaucomatous neurodegeneration and visual function.Molecular therapy. Nucleic acids · 2023Article
- Differential effects of SARM1 inhibition in traumatic glaucoma and EAE optic neuropathies.Molecular therapy. Nucleic acids · 2023Article
- Magnitude and Mechanism of Phrenic Long-term Facilitation Shift Between Daily Rest Versus Active Phase.Function (Oxford, England) · 2023Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Injured mature CNS axons do not regenerate in mammals. Deletion of PTEN, the negative regulator of PI3K, induces CNS axon regeneration through the activation of PI3K-mTOR signaling. We have conducted an extensive molecular dissection of the cross-regulating mechanisms in axon regeneration that involve the downstream effectors of PI3K, AKT and the two mTOR complexes (mTORC1 and mTORC2). We found that the predominant AKT isoform in CNS, AKT3, induces much more robust axon regeneration than AKT1 and that activation of mTORC1 and inhibition of GSK3β are two critical parallel pathways for AKT-induced axon regeneration. Surprisingly, phosphorylation of T308 and S473 of AKT play opposite roles in GSK3β phosphorylation and inhibition, by which mTORC2 and pAKT-S473 negatively regulate axon regeneration. Thus, our study revealed a complex neuron-intrinsic balancing mechanism involving AKT as the nodal point of PI3K, mTORC1/2 and GSK3β that coordinates both positive and negative cues to regulate adult CNS axon regeneration.
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Registered trials
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.