ArticleProceedings of the National Academy of Sciences of the United States of America2013
Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 1 of them a synthesis that pooled it.
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Who cites it
168 citing papers in PubMed, 1 synthesis or guideline pooled it, 267 citations in OpenAlex.
- Meta-analysis of transcriptomic changes in optic nerve injury and neurodegenerative models reveals a fundamental response to injury throughout the central nervous system.Molecular vision · 2017Pooled it
- HSV-1 reactivation as an emergent property of neuronal stress: implications for traumatic brain injury.Journal of neuroinflammation · 2026Review
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- DLK inhibition has sex-specific effects on neuroprotection and locomotor recovery after spinal cord injury.Experimental neurology · 2026Article
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- Synaptic control of retinal ganglion cell survival and axon regeneration.Molecular neurodegeneration · 2026Review
- Combinatorial chemistry identifies additional compounds that selectively inhibit DLK-dependent retrograde signaling while minimally affecting other axonal roles of DLK.Scientific reports · 2026Article
- MKK4 and MKK7 control degeneration of retinal ganglion cell somas and axons after glaucoma-relevant injury.Cell death discovery · 2025Article
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- Modeling neurodegeneration in the retina and strategies for developing pan-neurodegenerative therapies.Molecular neurodegeneration · 2025Review
- Pyruvate kinase deficiency links metabolic perturbations to neurodegeneration and axonal protection.Molecular metabolism · 2025Article
- Mitochondrial dynamics reveal potential to facilitate axonal regeneration after spinal cord injury.Journal of translational medicine · 2025Review
- Inhibiting acute, axonal DLK palmitoylation is neuroprotective and avoids deleterious effects of cell-wide DLK inhibition.Nature communications · 2025Article
- Quantitative phosphoproteomics reveals that nestin is a downstream target of dual leucine zipper kinase during retinoic acid-induced neuronal differentiation of Neuro-2a cells.BMC molecular and cell biology · 2025Article
- The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.Nature communications · 2025Article
- Engineered bio-functional material-based nerve guide conduits for optic nerve regeneration: a view from the cellular perspective, challenges and the future outlook.Regenerative biomaterials · 2025Review
- Preservation of Murine Whole Eyes With Supplemented UW Cold Storage Solution: Anatomical Considerations.Translational vision science & technology · 2024Article
- The Mechanisms of Neuroprotection by Topical Rho Kinase Inhibition in Experimental Mouse Glaucoma and Optic Neuropathy.Investigative ophthalmology & visual science · 2024Article
- Article
- Remyelination protects neurons from DLK-mediated neurodegeneration.Nature communications · 2024Article
108 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
32 authors at 13 institutions in 5 countries.
Funding
Abstract
Glaucoma, a major cause of blindness worldwide, is a neurodegenerative optic neuropathy in which vision loss is caused by loss of retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for the development of neuroprotective drugs, we developed a high-throughput RNA interference screen with primary RGCs and used it to screen the full mouse kinome. The screen identified dual leucine zipper kinase (DLK) as a key neuroprotective target in RGCs. In cultured RGCs, DLK signaling is both necessary and sufficient for cell death. DLK undergoes robust posttranscriptional up-regulation in response to axonal injury in vitro and in vivo. Using a conditional knockout approach, we confirmed that DLK is required for RGC JNK activation and cell death in a rodent model of optic neuropathy. In addition, tozasertib, a small molecule protein kinase inhibitor with activity against DLK, protects RGCs from cell death in rodent glaucoma and traumatic optic neuropathy models. Together, our results establish a previously undescribed drug/drug target combination in glaucoma, identify an early marker of RGC injury, and provide a starting point for the development of more specific neuroprotective DLK inhibitors for the treatment of glaucoma, nonglaucomatous forms of optic neuropathy, and perhaps other CNS neurodegenerations.
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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.