ArticleCell death & disease2018
Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 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
22 citing papers in PubMed, 31 citations in OpenAlex.
- Mitogen-activated protein kinase kinase 4 (MKK4) as a promising therapeutic target in liver diseases: a review.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- MKK4 and MKK7 control degeneration of retinal ganglion cell somas and axons after glaucoma-relevant injury.Cell death discovery · 2025Article
- Remyelination protects neurons from DLK-mediated neurodegeneration.Nature communications · 2024Article
- Remyelination protects neurons from DLK-mediated neurodegeneration.bioRxiv : the preprint server for biology · 2024Article
- Retinoblastoma: An update on genetic origin, classification, conventional to next-generation treatment strategies.Heliyon · 2024Review
- Pharmacological inhibition of the MAP2K7 kinase in human disease.Frontiers in oncology · 2024Review
- BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps.Molecular neurodegeneration · 2023Article
- BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps.Research square · 2023Article
- MKK4 Inhibitors-Recent Development Status and Therapeutic Potential.International journal of molecular sciences · 2023Review
- Identification of HSPA8 as an interacting partner of MAB21L2 and an important factor in eye development.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Review
- Worenine Prevents Solar Ultraviolet-Induced Sunburn by Inhibiting JNK2.Frontiers in pharmacology · 2022Article
- Mitogen-activated protein kinase kinase 7 in inflammatory, cancer, and neurological diseases.Frontiers in cell and developmental biology · 2022Review
- TAK1 inhibition increases proliferation and differentiation of chick retinal cells.Frontiers in cell and developmental biology · 2022Article
- MKK7-mediated phosphorylation of JNKs regulates the proliferation and apoptosis of human spermatogonial stem cells.World journal of stem cells · 2021Article
- Review
- Immunological and molecular basics of the primary open angle glaucoma pathomechanism.Central-European journal of immunology · 2021Review
- Endothelin 1-induced retinal ganglion cell death is largely mediated by JUN activation.Cell death & disease · 2020Article
- A broad perspective on the molecular regulation of retinal ganglion cell degeneration in glaucoma.Progress in brain research · 2020Review
- Axon injury signaling and compartmentalized injury response in glaucoma.Progress in retinal and eye research · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The mitogen-activated protein kinase (MAPK) pathway has been shown to be involved in both neurodevelopment and neurodegeneration. c-Jun N-terminal kinase (JNK), a MAPK important in retinal development and after optic nerve crush injury, is regulated by two upstream kinases: MKK4 and MKK7. The specific requirements of MKK4 and MKK7 in retinal development and retinal ganglion cell (RGC) death after axonal injury, however, are currently undefined. Optic nerve injury is an important insult in many neurologic conditions including traumatic, ischemic, inflammatory, and glaucomatous optic neuropathies. Mice deficient in Mkk4, Mkk7, and both Mkk4 and Mkk7 were generated. Immunohistochemistry was used to study the distribution and structure of retinal cell types and to assess RGC survival after optic nerve injury (mechanical controlled optic nerve crush (CONC)). Adult Mkk4- and Mkk7-deficient retinas had all retinal cell types, and with the exception of small areas of disrupted photoreceptor lamination in Mkk4-deficient mice, the retinas of both mutants were grossly normal. Deficiency of Mkk4 or Mkk7 reduced JNK signaling in RGCs after axonal injury and resulted in a significantly greater percentage of surviving RGCs 35 days after CONC as compared to wild-type controls (Mkk4: 51.5%, Mkk7: 29.1%, WT: 15.2%; p < 0.001). Combined deficiency of Mkk4 and Mkk7 caused failure of optic nerve formation, irregular retinal axonal trajectories, disruption of retinal lamination, clumping of RGC bodies, and dendritic fasciculation of dopaminergic amacrine cells. These results suggest that MKK4 and MKK7 may serve redundant and unique roles in molecular signaling important for retinal development and injury response following axonal insult.
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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.