Tumor Necrosis Factor-Like Weak Inducer of Apoptosis-Induced Neurodegeneration
| العنوان: | Tumor Necrosis Factor-Like Weak Inducer of Apoptosis-Induced Neurodegeneration |
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| المؤلفون: | Moritz J. Rossner, Kyungmin Hahm, John Lincecum, Ioana Potrovita, Martin H. Maurer, Armin Schneider, Markus Schwaninger, Monica Z. Wang, Wen Zhang, Linda C. Burkly |
| المصدر: | The Journal of Neuroscience. 24:8237-8244 |
| بيانات النشر: | Society for Neuroscience, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Male, Programmed cell death, Recombinant Fusion Proteins, Mice, Inbred Strains, Protein Serine-Threonine Kinases, Biology, Transfection, Antibodies, Receptors, Tumor Necrosis Factor, Brain Ischemia, Proinflammatory cytokine, Mice, Cell surface receptor, Neurobiology of Disease, medicine, Animals, Humans, Cells, Cultured, Cytokine TWEAK, Mice, Knockout, Neurons, Cell Death, Gene Expression Profiling, General Neuroscience, Neurodegeneration, NF-kappa B, Cerebral Infarction, medicine.disease, NFKB1, I-kappa B Kinase, Up-Regulation, Stroke, Disease Models, Animal, TWEAK Receptor, Apoptosis, Nerve Degeneration, Tumor Necrosis Factors, Cancer research, RNA, Tumor necrosis factor alpha, Apoptosis Regulatory Proteins, Carrier Proteins |
| الوصف: | Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor (TNF) family of cytokines. It has proangiogenic and proinflammatory propertiesin vivoand induces cell death in tumor cell lines. TWEAK effects are mediated by the membrane receptor Fn14. In a systematic search for genes regulated in a murine stroke model with the tag-sequencing technique massively parallel signature sequencing, we have identified TWEAK as an induced gene. After 24 hr of focal cerebral ischemiain vivoor oxygen glucose deprivation in primary cortical neurons, both TWEAK and its receptor Fn14 were significantly upregulated. TWEAK induced cell death in primary neurons. Transfection of a nuclear factor (NF)-κB-luciferase fusion gene demonstrated that TWEAK stimulated transcriptional activity of NF-κB through Fn14 and the IκB kinase. Inhibition of NF-κB reduced TWEAK-stimulated neuronal cell death, suggesting that NF-κB mediates TWEAK-induced neurodegeneration at least in part. Intraperitoneal injection of a neutralizing anti-TWEAK antibody significantly reduced the infarct size after 48 hr of permanent cerebral ischemia. In summary, our data show that TWEAK induces neuronal cell death and is involved in neurodegenerationin vivo. |
| تدمد: | 1529-2401 0270-6474 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e315603b3110573cd6f576b1ada104cf https://doi.org/10.1523/jneurosci.1089-04.2004 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e315603b3110573cd6f576b1ada104cf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292401 02706474 |
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