ArticleNeurobiology of disease2013
Proximal inhibition of p38 MAPK stress signaling prevents distal axonopathy.
Article in Neurobiology of disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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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.
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Who cites it
46 citing papers in PubMed, 77 citations in OpenAlex.
- Environmental Exposures and Oxidative Stress in Retinal and Optic Nerve Diseases: Mechanisms, Consequences, and Therapeutic Opportunities.Antioxidants (Basel, Switzerland) · 2026Review
- STING deficiency alleviates scar formation after glaucoma filtration surgery by suppressing p38 MAPK-induced inflammation in mice.Eye and vision (London, England) · 2026Article
- Ferroptosis and retinal ganglion cell death in glaucoma: Mechanisms and therapeutic approaches.Journal of pharmaceutical analysis · 2026Review
- Atypical p38 Kinase Signaling in Retinal Vascular Damage and Recovery.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Topical Application of a Collagen Mimetic Peptide Restores Peripapillary Scleral Stiffness Reduced by Ocular Stress.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Mechanobiology in the eye.npj biological physics and mechanics · 2025Review
- Preservation of Murine Whole Eyes With Supplemented UW Cold Storage Solution: Anatomical Considerations.Translational vision science & technology · 2024Article
- Regulated Cell Death of Retinal Ganglion Cells in Glaucoma: Molecular Insights and Therapeutic Potentials.Cellular and molecular neurobiology · 2023Review
- BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps.Molecular neurodegeneration · 2023Article
- Inhibition of p38 ameliorates axonal loss with modulation of autophagy in TNF-induced optic nerve damage.International ophthalmology · 2023Article
- Keratin8 Deficiency Aggravates Retinal Ganglion Cell Damage Under Acute Ocular Hypertension.Investigative ophthalmology & visual science · 2023Article
- BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps.Research square · 2023Article
- Review
- The Role of Axonal Transport in Glaucoma.International journal of molecular sciences · 2022Review
- Intraocular Delivery of a Collagen Mimetic Peptide Repairs Retinal Ganglion Cell Axons in Chronic and Acute Injury Models.International journal of molecular sciences · 2022Article
- Mechanisms of retinal ganglion cell injury following acute increases in intraocular pressure.Frontiers in ophthalmology · 2022Review
- Dysfunctional Homozygous VRK1-D263G Variant Impairs the Assembly of Cajal Bodies and DNA Damage Response in Hereditary Spastic Paraplegia.Neurology. Genetics · 2021Article
- Adaptive responses to neurodegenerative stress in glaucoma.Progress in retinal and eye research · 2021Review
- Neuroprotection by WldMolecular neurodegeneration · 2021Article
- Atypical p38 Signaling, Activation, and Implications for Disease.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The p38 mitogen-activated protein kinase (MAPK) isoforms are phosphorylated by a variety of stress stimuli in neurodegenerative disease and act as upstream activators of myriad pathogenic processes. Thus, p38 MAPK inhibitors are of growing interest as possible therapeutic interventions. Axonal dysfunction is an early component of most neurodegenerative disorders, including the most prevalent optic neuropathy, glaucoma. Sensitivity to intraocular pressure at an early stage disrupts anterograde transport along retinal ganglion cell (RGC) axons to projection targets in the brain with subsequent degeneration of the axons themselves; RGC body loss is much later. Here we show that elevated ocular pressure in rats increases p38 MAPK activation in retina, especially in RGC bodies. Topical eye-drop application of a potent and selective inhibitor of the p38 MAPK catalytic domain (Ro3206145) prevented both the degradation of anterograde transport to the brain and degeneration of axons in the optic nerve. Ro3206145 reduced in the retina phosphorylation of tau and heat-shock protein 27, both down-stream targets of p38 MAPK activation implicated in glaucoma, as well as expression of two inflammatory responses. We also observed increased p38 MAPK activation in mouse models. Thus, inhibition of p38 MAPK signaling in the retina may represent a therapeutic target for preventing early pathogenesis in optic neuropathies.
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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.