ArticlePloS one2012
In vivo evidence that TRAF4 is required for central nervous system myelin homeostasis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- TREML2 Modulates Microglial Phagocytosis of Myelin Debris via TLR9 in Chronic Cerebral Ischemia.Inflammation · 2025Article
- TRAF Family Member 4 Promotes Cardiac Hypertrophy Through the Activation of the AKT Pathway.Journal of the American Heart Association · 2023Article
- TRAF4 Silencing Induces Cell Apoptosis and Improves Retinoic Acid Sensitivity in Human Neuroblastoma.Neurochemical research · 2023Article
- Genome-wide analysis of genes encoding core components of the ubiquitin system during cerebral cortex development.Molecular brain · 2022Article
- The Research Progress in Physiological and Pathological Functions of TRAF4.Frontiers in oncology · 2022Review
- The Role of Tumor Necrosis Factor Associated Factors (TRAFs) in Vascular Inflammation and Atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
- The Implication of Reticulons (RTNs) in Neurodegenerative Diseases: From Molecular Mechanisms to Potential Diagnostic and Therapeutic Approaches.International journal of molecular sciences · 2021Review
- Lactosylceramide induced by elastin-derived peptides decreases adipocyte differentiation.Journal of physiology and biochemistry · 2020Article
- TRAF molecules in inflammation and inflammatory diseases.Current pharmacology reports · 2018Article
- Genetic Alterations of TRAF Proteins in Human Cancers.Frontiers in immunology · 2018Review
- The tumor suppressive miR-302c-3p inhibits migration and invasion of hepatocellular carcinoma cells by targeting TRAF4.Journal of Cancer · 2018Article
- Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo.Scientific reports · 2017Article
- TRAF4 Regulates Migration, Invasion, and Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Hepatocellular Carcinoma.Oncology research · 2017Article
- Quantitative Phosphoproteomics Reveals a Role for Collapsin Response Mediator Protein 2 in PDGF-Induced Cell Migration.Scientific reports · 2017Article
- Agenesis of the corpus callosum in Nogo receptor deficient mice.The Journal of comparative neurology · 2017Article
- Article
- TRAF4 promotes the growth and invasion of colon cancer through the Wnt/β-catenin pathway.International journal of clinical and experimental pathology · 2015Article
- Overview about the localization of nanoparticles in tissue and cellular context by different imaging techniques.Beilstein journal of nanotechnology · 2015Review
- Minocycline upregulates pro-survival genes and downregulates pro-apoptotic genes in experimental glaucoma.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2014Article
- The dual behavior of PCSK9 in the regulation of apoptosis is crucial in Alzheimer's disease progression (Review).Biomedical reports · 2014Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are major signal transducers for the TNF and interleukin-1/Toll-like receptor superfamilies. However, TRAF4 does not fit the paradigm of TRAF function in immune and inflammatory responses. Its physiological and molecular functions remain poorly understood. Behavorial analyses show that TRAF4-deficient mice (TRAF4-KO) exhibit altered locomotion coordination typical of ataxia. TRAF4-KO central nervous system (CNS) ultrastructure shows strong myelin perturbation including disorganized layers and disturbances in paranode organization. TRAF4 was previously reported to be expressed by CNS neurons. Using primary cell culture, we now show that TRAF4 is also expressed by oligodendrocytes, at all stages of their differentiation. Moreover, histology and electron microscopy show degeneration of a high number of Purkinje cells in TRAF4-KO mice, that was confirmed by increased expression of the Bax pro-apoptotic marker (immunofluorescence), TUNEL analysis, and caspase-3 activation and PARP1 cleavage (western blotting). Consistent with this phenotype, MAG and NogoA, two myelin-induced neurite outgrowth inhibitors, and their neuron partners, NgR and p75NTR were overexpressed (Q-RT-PCR and western blotting). The strong increased phosphorylation of Rock2, a RhoA downstream target, indicated that the NgR/p75NTR/RhoA signaling pathway, known to induce actin cytoskeleton rearrangement that favors axon regeneration inhibition and neuron apoptosis, is activated in the absence of TRAF4 (western blotting). Altogether, these results provide conclusive evidence for the pivotal contribution of TRAF4 to myelination and to cerebellar homeostasis, and link the loss of TRAF4 function to demyelinating or neurodegenerative diseases.
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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.