Mechanisms Underlying Metabolic and Neural Defects in Zebrafish and Human Multiple Acyl-CoA Dehydrogenase Deficiency (MADD)
| العنوان: | Mechanisms Underlying Metabolic and Neural Defects in Zebrafish and Human Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) |
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| المؤلفون: | Paul C. Scherer, Christopher A. Coutts, Michael J. Bennett, Declan W. Ali, Corey T. Watson, Sarah M. Gibbs, Rita J. Balice-Gordon, Marion O. Scott, Gregory B. Willer, Yuanquan Song, Jessica A. Panzer, Ronald G. Gregg, Mary A. Selak |
| المصدر: | PLoS ONE, Vol 4, Iss 12, p e8329 (2009) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Iron-Sulfur Proteins, Peroxisome Proliferator-Activated Receptors, Carboxylic Acids, lcsh:Medicine, Mitochondrion, Nervous System, 0302 clinical medicine, Glycolysis, Cloning, Molecular, Extracellular Signal-Regulated MAP Kinases, Multiple Acyl Coenzyme A Dehydrogenase Deficiency, lcsh:Science, Multiple Acyl-CoA Dehydrogenase Deficiency, Zebrafish, Neurons, Oxidoreductases Acting on CH-NH Group Donors, 0303 health sciences, Multidisciplinary, biology, Neurogenesis, Mitochondria, 3. Good health, Cell biology, Phenotype, Research Article, Electron-Transferring Flavoproteins, Oxidative phosphorylation, Neurological Disorders, Electron-transferring flavoprotein, 03 medical and health sciences, Carnitine, Animals, Humans, Cell Proliferation, 030304 developmental biology, lcsh:R, Infant, Newborn, Infant, nutritional and metabolic diseases, Fibroblasts, Oligonucleotides, Antisense, biology.organism_classification, Molecular biology, Enzyme Activation, Developmental Biology/Neurodevelopment, Anaerobic glycolysis, Mutation, biology.protein, lcsh:Q, 030217 neurology & neurosurgery, Neuroscience |
| الوصف: | In humans, mutations in electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH) lead to MADD/glutaric aciduria type II, an autosomal recessively inherited disorder characterized by a broad spectrum of devastating neurological, systemic and metabolic symptoms. We show that a zebrafish mutant in ETFDH, xavier, and fibroblast cells from MADD patients demonstrate similar mitochondrial and metabolic abnormalities, including reduced oxidative phosphorylation, increased aerobic glycolysis, and upregulation of the PPARG-ERK pathway. This metabolic dysfunction is associated with aberrant neural proliferation in xav, in addition to other neural phenotypes and paralysis. Strikingly, a PPARG antagonist attenuates aberrant neural proliferation and alleviates paralysis in xav, while PPARG agonists increase neural proliferation in wild type embryos. These results show that mitochondrial dysfunction, leading to an increase in aerobic glycolysis, affects neurogenesis through the PPARG-ERK pathway, a potential target for therapeutic intervention. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d0f7ae63d4110937bf15e845cf582858Test https://doi.org/10.1371/journal.pone.0008329Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d0f7ae63d4110937bf15e845cf582858 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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