Academic Journal
Metabolic Reprogramming in Amyotrophic Lateral Sclerosis
| العنوان: | Metabolic Reprogramming in Amyotrophic Lateral Sclerosis |
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| المؤلفون: | Szelechowski, M., Amoedo, N., Obre, E., Léger, Claire, Allard, L., Bonneu, M., Claverol, S., Lacombe, Didier, Oliet, Stéphane, Chevallier, S., Le Masson, Gwendal, Rossignol, Rodrigue |
| المساهمون: | 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: | ISSN: 2045-2322. |
| بيانات النشر: | HAL CCSD Nature Publishing Group |
| سنة النشر: | 2018 |
| المجموعة: | Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| مصطلحات موضوعية: | [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] |
| الوصف: | International audience ; 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/29500423; inserm-02647599; https://inserm.hal.science/inserm-02647599; https://inserm.hal.science/inserm-02647599/document; https://inserm.hal.science/inserm-02647599/file/s41598-018-22318-5.pdf; PUBMED: 29500423; PUBMEDCENTRAL: PMC5834494 |
| DOI: | 10.1038/s41598-018-22318-5 |
| الاتاحة: | https://inserm.hal.science/inserm-02647599 https://inserm.hal.science/inserm-02647599/document https://inserm.hal.science/inserm-02647599/file/s41598-018-22318-5.pdf https://doi.org/10.1038/s41598-018-22318-5 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.3F0B0777 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-018-22318-5 |
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