Metabolic Reprogramming in Amyotrophic Lateral Sclerosis
| العنوان: | Metabolic Reprogramming in Amyotrophic Lateral Sclerosis |
|---|---|
| المؤلفون: | Rodrigue Rossignol, Emilie Obre, G. Le Masson, Marc Bonneu, Didier Lacombe, C. Léger, Marion Szelechowski, L. Allard, Stéphane Claverol, S. Oliet, Nivea Dias Amoedo, S. Chevallier |
| المساهمون: | Oliet, Stephane, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellomet [CHU Pellegrin, Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2] |
| المصدر: | Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) Scientific Reports Scientific Reports, Nature Publishing Group, 2018, 8 (1), pp.3953. ⟨10.1038/s41598-018-22318-5⟩ |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Proteome, Bioenergetics, Cell Survival, lcsh:Medicine, Oxidative phosphorylation, Biology, Article, Oxidative Phosphorylation, Mice, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, medicine, Animals, Humans, TRNA aminoacylation, Uncoupling Protein 2, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Viability assay, Amyotrophic lateral sclerosis, Cell adhesion, lcsh:Science, Beta oxidation, Skin, Motor Neurons, Multidisciplinary, Superoxide Dismutase, Amyotrophic Lateral Sclerosis, Fatty Acids, lcsh:R, Fibroblasts, medicine.disease, Cell biology, Disease Models, Animal, 030104 developmental biology, Spinal Cord, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Q, Oxidation-Reduction, 030217 neurology & neurosurgery |
| الوصف: | Mitochondrial dysfunction in the spinal cord is a hallmark of amyotrophic lateral sclerosis (ALS), but the neurometabolic alterations during early stages of the disease remain unknown. Here, we investigated the bioenergetic and proteomic changes in ALS mouse motor neurons and patients’ skin fibroblasts. We first observed that SODG93A mice presymptomatic motor neurons display alterations in the coupling efficiency of oxidative phosphorylation, along with fragmentation of the mitochondrial network. The proteome of presymptomatic ALS mice motor neurons also revealed a peculiar metabolic signature with upregulation of most energy-transducing enzymes, including the fatty acid oxidation (FAO) and the ketogenic components HADHA and ACAT2, respectively. Accordingly, FAO inhibition altered cell viability specifically in ALS mice motor neurons, while uncoupling protein 2 (UCP2) inhibition recovered cellular ATP levels and mitochondrial network morphology. These findings suggest a novel hypothesis of ALS bioenergetics linking FAO and UCP2. Lastly, we provide a unique set of data comparing the molecular alterations found in human ALS patients’ skin fibroblasts and SODG93A mouse motor neurons, revealing conserved changes in protein translation, folding and assembly, tRNA aminoacylation and cell adhesion processes. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7163e99658cb79eca7ca1aa0c7249aaa http://link.springer.com/article/10.1038/s41598-018-22318-5 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7163e99658cb79eca7ca1aa0c7249aaa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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