ArticleProceedings of the National Academy of Sciences of the United States of America2013
DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury.
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 221 papers, 1 of them a synthesis that pooled it.
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Who cites it
221 citing papers in PubMed, 1 synthesis or guideline pooled it, 338 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
- A Phase 1 study of GDC-0134, a dual leucine zipper kinase inhibitor, in ALS.Annals of clinical and translational neurology · 2022Trial
- Oxidative signaling thresholds shape vulnerability in the central and peripheral nervous systems.PLoS biology · 2026Article
- Heat shock protein 40 enhances axon regeneration in a mouse model of traumatic optic neuropathy.Neural regeneration research · 2026Article
- Experimental upregulation of Lancl1 promotes axon regeneration after optic nerve injury in vivo.Experimental neurology · 2026Article
- Wallerian Degeneration and Nerve Regeneration-A Review of Cellular and Molecular Events.International journal of molecular sciences · 2026Review
- Article
- DLK inhibition has sex-specific effects on neuroprotection and locomotor recovery after spinal cord injury.Experimental neurology · 2026Article
- Protein kinases as therapeutic targets in Alzheimer's disease: challenges, insights, and new frontiers.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Article
- 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
- Technological advances in axonal regeneration and structural plasticity: optogenetics, single-cell omics, and tissue clearing.Frontiers in cellular neuroscience · 2026Review
- DLK orchestrates a modular transcriptional response to axon injury with separate roles for Fos and Jun.PLoS genetics · 2025Article
- Emerging Molecular PET Imaging for Cell Death in Neurodegenerative Diseases.Journal of medicinal chemistry · 2025Review
- Article
- Pyruvate kinase deficiency links metabolic perturbations to neurodegeneration and axonal protection.Molecular metabolism · 2025Article
- DLK/JNK3 Upregulation Aggravates Hair Cell Senescence in Mice Cochleae via Excessive Autophagy.Aging cell · 2025Article
- Functional significance of commonly regulated genes in mechanically and chemically induced retinal ganglion cell death in rat eyes.Scientific reports · 2025Article
- Mitochondrial dynamics reveal potential to facilitate axonal regeneration after spinal cord injury.Journal of translational medicine · 2025Review
161 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
10 authors at 1 institution.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cell intrinsic factors that determine whether a neuron regenerates or undergoes apoptosis in response to axonal injury are not well defined. Here we show that the mixed-lineage dual leucine zipper kinase (DLK) is an essential upstream mediator of both of these divergent outcomes in the same cell type. Optic nerve crush injury leads to rapid elevation of DLK protein, first in the axons of retinal ganglion cells (RGCs) and then in their cell bodies. DLK is required for the majority of gene expression changes in RGCs initiated by injury, including induction of both proapoptotic and regeneration-associated genes. Deletion of DLK in retina results in robust and sustained protection of RGCs from degeneration after optic nerve injury. Despite this improved survival, the number of axons that regrow beyond the injury site is substantially reduced, even when the tumor suppressor phosphatase and tensin homolog (PTEN) is deleted to enhance intrinsic growth potential. These findings demonstrate that these seemingly contradictory responses to injury are mechanistically coupled through a DLK-based damage detection mechanism.
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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.