ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Boosting Central Nervous System Axon Regeneration by Circumventing Limitations of Natural Cytokine Signaling.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 103 citations in OpenAlex.
- Article
- The role of immune regulation in peripheral nerve regeneration: functions of inflammatory cells and cytokines.Frontiers in pharmacology · 2026Review
- Retrograde viral delivery of hyper-IL-6 activates Stat3 in corticospinal tract neurons but causes severe tremors and weight loss in adult mice.bioRxiv : the preprint server for biology · 2025Article
- Preserving blood-retinal barrier integrity: a path to retinal ganglion cell protection in glaucoma and traumatic optic neuropathy.Cell regeneration (London, England) · 2025Review
- Srebf2 mediates successful optic nerve axon regeneration via the mevalonate synthesis pathway.Molecular neurodegeneration · 2025Article
- Pharmacological modulation of PI3K/PTEN/Akt/mTOR/ERK signaling pathways in ischemic injury: a mechanistic perspective.Metabolic brain disease · 2025Review
- Mechanosensitive channel of large conductance enhances the mechanical stretching-induced upregulation of glycolysis and oxidative metabolism in Schwann cells.Cell communication and signaling : CCS · 2024Article
- Cell-free fat extract promotes axon regeneration and retinal ganglion cells survival in traumatic optic neuropathy.Frontiers in cellular neuroscience · 2024Article
- Inhibition of microtubule detyrosination by parthenolide facilitates functional CNS axon regeneration.eLife · 2023Article
- Improving adeno-associated viral (AAV) vector-mediated transgene expression in retinal ganglion cells: comparison of five promoters.Gene therapy · 2023Article
- Immune stimulation recruits a subset of pro-regenerative macrophages to the retina that promotes axonal regrowth of injured neurons.Acta neuropathologica communications · 2023Article
- Transneuronal Delivery of Cytokines to Stimulate Mammalian Spinal Cord Regeneration.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling.Neural regeneration research · 2022Review
- Transneuronal delivery of designer cytokines: perspectives for spinal cord injury.Neural regeneration research · 2022Article
- Neuronal Redevelopment and the Regeneration of Neuromodulatory Axons in the Adult Mammalian Central Nervous System.Frontiers in cellular neuroscience · 2022Review
- The Pathogenesis and Therapeutic Approaches of Diabetic Neuropathy in the Retina.International journal of molecular sciences · 2021Review
- MMP2 Modulates Inflammatory Response during Axonal Regeneration in the Murine Visual System.Cells · 2021Article
- CXCR4/CXCL12-mediated entrapment of axons at the injury site compromises optic nerve regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Transneuronal delivery of hyper-interleukin-6 enables functional recovery after severe spinal cord injury in mice.Nature communications · 2021Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinal ganglion cells (RGCs) do not normally regenerate injured axons, but die upon axotomy. Although IL-6-like cytokines are reportedly neuroprotective and promote optic nerve regeneration, their overall regenerative effects remain rather moderate. Here, we hypothesized that direct activation of the gp130 receptor by the designer cytokine hyper-IL-6 (hIL-6) might induce stronger RGC regeneration than natural cytokines. Indeed, hIL-6 stimulated neurite growth of adult cultured RGCs with significantly higher efficacy than CNTF or IL-6. This neurite growth promoting effect could be attributed to stronger activation of the JAK/STAT3 and PI3K/AKT/mTOR signaling pathways and was also observed in peripheral dorsal root ganglion neurons. Moreover, hIL-6 abrogated axon growth inhibition by central nervous system (CNS) myelin. Remarkably, continuous hIL-6 expression upon RGC-specific AAV transduction after optic nerve crush exerted stronger axon regeneration than other known regeneration promoting treatments such as lens injury and PTEN knockout, with some axons growing through the optic chiasm 6 weeks after optic nerve injury. Combination of hIL-6 with RGC-specific PTEN knockout further enhanced optic nerve regeneration. Therefore, direct activation of gp130 signaling might be a novel, clinically applicable approach for robust CNS repair.
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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.