ArticleeLife2017
Dual leucine zipper kinase-dependent PERK activation contributes to neuronal degeneration following insult.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 100 citations in OpenAlex.
- DNL343 and Disease Progression in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.JAMA network open · 2026Trial
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- 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
- Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS.The Journal of clinical investigation · 2025Article
- Chronic integrated stress response causes dysregulated cholesterol synthesis in white matter disease.JCI insight · 2025Article
- Article
- A lead role for a "secondary" axonal injury response.Neural regeneration research · 2025Article
- The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.Nature communications · 2025Article
- DLK-dependent axonal mitochondrial fission drives degeneration after axotomy.Nature communications · 2024Article
- Chemogenetic neuronal silencing decouples c-Jun activation from cell death in the temporal cortex.The European journal of neuroscience · 2024Article
- Article
- The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.bioRxiv : the preprint server for biology · 2024Article
- Article
- DLK-dependent axonal mitochondrial fission drives degeneration following axotomy.bioRxiv : the preprint server for biology · 2024Article
- DLK signaling in axotomized neurons triggers complement activation and loss of upstream synapses.Cell reports · 2024Article
- Review
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Targeting synapse function and loss for treatment of neurodegenerative diseases.Nature reviews. Drug discovery · 2024Review
- The response of Dual-leucine zipper kinase (DLK) to nocodazole: Evidence for a homeostatic cytoskeletal repair mechanism.PloS one · 2024Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PKR-like endoplasmic reticulum kinase (PERK) arm of the Integrated Stress Response (ISR) is implicated in neurodegenerative disease, although the regulators and consequences of PERK activation following neuronal injury are poorly understood. Here we show that PERK signaling is a component of the mouse MAP kinase neuronal stress response controlled by the Dual Leucine Zipper Kinase (DLK) and contributes to DLK-mediated neurodegeneration. We find that DLK-activating insults ranging from nerve injury to neurotrophin deprivation result in both c-Jun N-terminal Kinase (JNK) signaling and the PERK- and ISR-dependent upregulation of the Activating Transcription Factor 4 (ATF4). Disruption of PERK signaling delays neurodegeneration without reducing JNK signaling. Furthermore, DLK is both sufficient for PERK activation and necessary for engaging the ISR subsequent to JNK-mediated retrograde injury signaling. These findings identify DLK as a central regulator of not only JNK but also PERK stress signaling in neurons, with both pathways contributing to neurodegeneration.
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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.