ArticleeLife2016
An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 83 citations in OpenAlex.
- Replating Induces mTOR-Dependent Rescue of Protein Synthesis in Charcot-Marie-Tooth Diseased Neurons.eNeuro · 2026Article
- Synaptic control of retinal ganglion cell survival and axon regeneration.Molecular neurodegeneration · 2026Review
- Dual leucine zipper-bearing kinase DLK is necessary for cell autonomous regulation of insulin sensitivity.Molecular metabolism · 2025Article
- 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
- 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
- Multiple regulators constrain the abundance of Caenorhabditis elegans DLK-1 in ciliated sensory neurons.G3 (Bethesda, Md.) · 2025Article
- Neurons Are Not All the Same: Diversity in Neuronal Populations and Their Intrinsic Responses to Spinal Cord Injury.ASN neuro · 2025Review
- Role and Interplay of Different Signaling Pathways Involved in Sciatic Nerve Regeneration.Journal of molecular neuroscience : MN · 2024Review
- Article
- Dendrite injury triggers neuroprotection in Drosophila models of neurodegenerative disease.Scientific reports · 2024Article
- Voltage-gated calcium channels act upstream of adenylyl cyclase Ac78C to promote timely initiation of dendrite regeneration.PLoS genetics · 2024Article
- Arrestin-3-assisted activation of JNK3 mediates dopaminergic behavioral sensitization.Cell reports. Medicine · 2024Article
- Review
- Brief Electrical Stimulation Promotes Recovery after Surgical Repair of Injured Peripheral Nerves.International journal of molecular sciences · 2024Review
- An intraflagellar transport dependent negative feedback regulates the MAPKKK DLK-1 to protect cilia from degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Brief Oxygen Exposure after Traumatic Brain Injury Hastens Recovery and Promotes Adaptive Chronic Endoplasmic Reticulum Stress Responses.International journal of molecular sciences · 2023Article
- Increase of c-FOS promoter transcriptional activity by the dual leucine zipper kinase.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Axonal Regeneration: Underlying Molecular Mechanisms and Potential Therapeutic Targets.Biomedicines · 2022Review
- A cilia-independent function of BBSome mediated by DLK-MAPK signaling in C. elegans photosensation.Developmental cell · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
A broadly known method to stimulate the growth potential of axons is to elevate intracellular levels of cAMP, however the cellular pathway(s) that mediate this are not known. Here we identify the Dual Leucine-zipper Kinase (DLK, Wnd in Drosophila) as a critical target and effector of cAMP in injured axons. DLK/Wnd is thought to function as an injury 'sensor', as it becomes activated after axonal damage. Our findings in both Drosophila and mammalian neurons indicate that the cAMP effector kinase PKA is a conserved and direct upstream activator of Wnd/DLK. PKA is required for the induction of Wnd signaling in injured axons, and DLK is essential for the regenerative effects of cAMP in mammalian DRG neurons. These findings link two important mediators of responses to axonal injury, DLK/Wnd and cAMP/PKA, into a unified and evolutionarily conserved molecular pathway for stimulating the regenerative potential of injured axons.
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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.