ArticleProceedings of the National Academy of Sciences of the United States of America2016
Promoting axon regeneration in the adult CNS by modulation of the melanopsin/GPCR signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- Frontiers of optic nerve regeneration research: an analysis of the top 100 most influential articles in the field from 2005 to 2025.Frontiers in neuroscience · 2025Pooled it
- Article
- Identification of a natively resilient but poorly regenerating retinal ganglion cell type in the G protein-coupled receptor 88-Cre transgenic mouse.Neural regeneration research · 2026Article
- A paradoxical relationship between mitochondrial calcium regulation and retinal ganglion cell degeneration after axon damage.bioRxiv : the preprint server for biology · 2026Article
- Melanopsin regulates axonal translation underlying retinohypothalamic circuit assembly.bioRxiv : the preprint server for biology · 2026Article
- Select NSAIDs enhance peripheral nerve growth and calcium signaling through PPARγ activation.Molecular and cellular neurosciences · 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
- Synaptic control of retinal ganglion cell survival and axon regeneration.Molecular neurodegeneration · 2026Review
- Optic nerve injury impairs intrinsic mechanisms underlying electrical activity in a resilient retinal ganglion cell.The Journal of physiology · 2025Article
- Serotonin neuromodulation directs optic nerve regeneration.Development (Cambridge, England) · 2025Article
- Dual Role of Ibuprofen and Indomethacin in Promoting Peripheral Nerve RegenerationTissue engineering. Part A · 2025Article
- Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion.Communications biology · 2025Article
- Chronic motoneuronal activation enhanced axonal regeneration and functional recovery after brachial plexus injury.Journal of orthopaedic translation · 2025Article
- Chromosome-level genome assembly and single-cell analysis unveil molecular mechanisms of arm regeneration in the ophiuroid Ophiura sarsii vadicola.Genome biology · 2025Article
- Functional optic tract rewiring via subtype- and target-specific axonal regeneration and presynaptic activity enhancement.Nature communications · 2025Article
- Neuroprotective Effect of the Combination of Citicoline and CoQ10 in a Mouse Model of Ocular Hypertension.Antioxidants (Basel, Switzerland) · 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
- Modulating amacrine cell-derived dopamine signaling promotes optic nerve regeneration and preserves visual function.Science advances · 2024Article
- Calcium plays an essential role in early-stage dendrite injury detection and regeneration.Progress in neurobiology · 2024Article
- Perinuclear compartment controls calcineurin/MEF2 signaling for axonal outgrowth of hippocampal neurons.Frontiers in molecular neuroscience · 2024Article
19 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
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell-type-specific G protein-coupled receptor (GPCR) signaling regulates distinct neuronal responses to various stimuli and is essential for axon guidance and targeting during development. However, its function in axonal regeneration in the mature CNS remains elusive. We found that subtypes of intrinsically photosensitive retinal ganglion cells (ipRGCs) in mice maintained high mammalian target of rapamycin (mTOR) levels after axotomy and that the light-sensitive GPCR melanopsin mediated this sustained expression. Melanopsin overexpression in the RGCs stimulated axonal regeneration after optic nerve crush by up-regulating mTOR complex 1 (mTORC1). The extent of the regeneration was comparable to that observed after phosphatase and tensin homolog (Pten) knockdown. Both the axon regeneration and mTOR activity that were enhanced by melanopsin required light stimulation and Gq/11 signaling. Specifically, activating Gq in RGCs elevated mTOR activation and promoted axonal regeneration. Melanopsin overexpression in RGCs enhanced the amplitude and duration of their light response, and silencing them with Kir2.1 significantly suppressed the increased mTOR signaling and axon regeneration that were induced by melanopsin. Thus, our results provide a strategy to promote axon regeneration after CNS injury by modulating neuronal activity through GPCR signaling.
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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.