ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
ZPK/DLK, a mitogen-activated protein kinase kinase kinase, is a critical mediator of programmed cell death of motoneurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- A Phase 1 study of GDC-0134, a dual leucine zipper kinase inhibitor, in ALS.Annals of clinical and translational neurology · 2022Trial
- Article
- 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
- Regulation of axonal regeneration after mammalian spinal cord injury.Nature reviews. Molecular cell biology · 2023Review
- Article
- Dual Leucine Zipper Kinase Is Constitutively Active in the Adult Mouse Brain and Has Both Stress-Induced and Homeostatic Functions.International journal of molecular sciences · 2020Article
- Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease.Frontiers in aging neuroscience · 2020Review
- Motor neuron loss in SMA is not associated with somal stress-activated JNK/c-Jun signaling.Human molecular genetics · 2019Article
- Intrathecal Injection of Dual Zipper Kinase shRNA Alleviating the Neuropathic Pain in a Chronic Constrictive Nerve Injury Model.International journal of molecular sciences · 2018Article
- Zika virus-induced acute myelitis and motor deficits in adult interferon αβ/γ receptor knockout mice.Journal of neurovirology · 2018Article
- Distinct homeostatic modulations stabilize reduced postsynaptic receptivity in response to presynaptic DLK signaling.Nature communications · 2018Article
- Article
- DLK silencing attenuated neuron apoptosis through JIP3/MA2K7/JNK pathway in early brain injury after SAH in rats.Neurobiology of disease · 2017Article
- Functional decline at the aging neuromuscular junction is associated with altered laminin-α4 expression.Aging · 2017Article
- Retrograde apoptotic signaling by the p75 neurotrophin receptor.Neuronal signaling · 2017Review
- Tozasertib attenuates neuronal apoptosis via DLK/JIP3/MA2K7/JNK pathway in early brain injury after SAH in rats.Neuropharmacology · 2016Article
- Leucine Zipper-bearing Kinase promotes axon growth in mammalian central nervous system neurons.Scientific reports · 2016Article
- Dual leucine zipper kinase regulates expression of axon guidance genes in mouse neuronal cells.Neural development · 2016Article
- Rho1-Wnd signaling regulates loss-of-cell polarity-induced cell invasion in Drosophila.Oncogene · 2016Article
- Intrinsic Axonal Growth and the Drive for Regeneration.Frontiers in neuroscience · 2016Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Activation of mitogen-activated protein kinase pathways is critically involved in naturally occurring programmed cell death of motoneurons during development, but the upstream mediators remain undetermined. We found that mice deficient in ZPK, also called DLK (ZPK/DLK), an upstream kinase in these pathways, have twice as many spinal motoneurons as do their wild-type littermates. Nuclear HB9/MNX1-positive motoneuron pools were generated similarly in the spinal cord of both ZPK/DLK-deficient and wild-type embryos. Thereafter, however, significantly less apoptotic motoneurons were found in ZPK/DLK-deficient embryos compared with wild-type embryos, resulting in retention of excess numbers of motoneurons after birth. Notably, these excess motoneurons remained viable without atrophic changes in the ZPK/DLK-deficient mice surviving into adulthood. Analysis of the diaphragm and the phrenic nerve revealed that clustering and innervation of neuromuscular junctions were indistinguishable between ZPK/DLK-deficient and wild-type mice, whereas the proximal portion of the phrenic nerve of ZPK/DLK-deficient mice contained significantly more axons than the distal portion. This result supports the hypothesis that some excess ZPK/DLK-deficient motoneurons survived without atrophy despite failure to establish axonal contact with their targets. This study provides compelling evidence for a critical role for ZPK/DLK in naturally occurring programmed cell death of motoneurons and suggests that ZPK/DLK could become a strategic therapeutic target in motor neuron diseases in which aberrant activation of the apoptogenic cascade is involved.
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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.