ArticleThe Journal of cell biology2015
Oxidative stress-dependent phosphorylation activates ZNRF1 to induce neuronal/axonal degeneration.
Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- Establishment of a machine learning prediction model for Wallerian degeneration after ischemic stroke.Frontiers in medicine · 2026Article
- L-Glutamate enables the EGFR-MEK-ERK-mTFB2 axis to enhance mitochondrial biogenesis in intestinal stem cells.Stem cell research & therapy · 2025Article
- Myeloid ZNRF1 suppresses autoimmune demyelination and neuroinflammation by regulating MHC-II-mediated T cell activation.Journal of neuroinflammation · 2025Article
- Enhancing peripheral nerve regeneration with rehabilitation and biomaterial-driven drug delivery strategies.Progress in biomedical engineering (Bristol, England) · 2025Review
- Basic Pathological Mechanisms in Peripheral Nerve Diseases.International journal of molecular sciences · 2025Review
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- Genome-Wide Mendelian Randomization Identifies Ferroptosis-Related Drug Targets for Alzheimer's Disease.Journal of Alzheimer's disease reports · 2024Article
- Optogenetics in Alzheimer's Disease: Focus on Astrocytes.Antioxidants (Basel, Switzerland) · 2023Review
- The Src-ZNRF1 axis controls TLR3 trafficking and interferon responses to limit lung barrier damage.The Journal of experimental medicine · 2023Article
- Novel insights into the mechanism of reactive oxygen species-mediated neurodegeneration.Neural regeneration research · 2023Review
- Neuroprotective Effects of Licochalcone D in Oxidative-Stress-Induced Primitive Neural Stem Cells from Parkinson's Disease Patient-Derived iPSCs.Biomedicines · 2023Article
- Repurposed anti-cancer epidermal growth factor receptor inhibitors: mechanisms of neuroprotective effects in Alzheimer's disease.Neural regeneration research · 2022Review
- Typical and atypical properties of peripheral nerve allografts enable novel strategies to repair segmental-loss injuries.Journal of neuroinflammation · 2022Review
- Network Pharmacology and Bioinformatics Methods Reveal the Mechanism of Berberine in the Treatment of Ischaemic Stroke.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Mitochondrial Reactive Oxygen Species Mediate Activation of TRPV1 and Calcium Entry Following Peripheral Sensory Axotomy.Frontiers in molecular neuroscience · 2022Article
- Angiogenesis and nerve regeneration induced by local administration of plasmidNeural regeneration research · 2021Article
- Article
- Pharmacological Inhibition of Brain EGFR Activation By a BBB-penetrating Inhibitor, AZD3759, Attenuates α-synuclein Pathology in a Mouse Model of α-Synuclein Propagation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Small noncoding vault RNA modulates synapse formation by amplifying MAPK signaling.The Journal of cell biology · 2021Article
- Role of the Polyol Pathway in Locomotor Recovery and Wallerian Degeneration after Spinal Cord Contusion Injury.Neurotrauma reports · 2021Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress is a well-known inducer of neuronal apoptosis and axonal degeneration. We previously showed that the E3 ubiquitin ligase ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B activation. We now demonstrate that oxidative stress serves as an activator of the ubiquitin ligase activity of ZNRF1 by inducing epidermal growth factor receptor (EGFR)-mediated phosphorylation at the 103rd tyrosine residue and that the up-regulation of ZNRF1 activity by oxidative stress leads to neuronal apoptosis and Wallerian degeneration. We also show that nicotinamide adenine dinucleotide phosphate-reduced oxidase activity is required for the EGFR-dependent phosphorylation-induced activation of ZNRF1 and resultant AKT degradation via the ubiquitin proteasome system to induce Wallerian degeneration. These results indicate the pathophysiological significance of the EGFR-ZNRF1 pathway induced by oxidative stress in the regulation of neuronal apoptosis and Wallerian degeneration. A deeper understanding of the regulatory mechanism for ZNRF1 catalytic activity via phosphorylation will provide a potential therapeutic avenue for 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.