Metabolic Reprogramming in Amyotrophic Lateral Sclerosis.
作者： S. Claverol , D. Lacombe , S. Oliet , S. Chevallier , G. Le Masson
DOI: 10.1038/S41598-018-22318-5
关键词:
摘要: Mitochondrial dysfunction in the spinal cord is a hallmark of amyotrophic lateral sclerosis (ALS), but neurometabolic alterations during early stages disease remain unknown. Here, we investigated bioenergetic and proteomic changes ALS mouse motor neurons patients' skin fibroblasts. We first observed that SODG93A mice presymptomatic display coupling efficiency oxidative phosphorylation, along with fragmentation mitochondrial network. The proteome also revealed peculiar metabolic signature upregulation most energy-transducing enzymes, including fatty acid oxidation (FAO) ketogenic components HADHA ACAT2, respectively. Accordingly, FAO inhibition altered cell viability specifically neurons, while uncoupling protein 2 (UCP2) recovered cellular ATP levels network morphology. These findings suggest novel hypothesis bioenergetics linking UCP2. Lastly, provide unique set data comparing molecular found human fibroblasts revealing conserved translation, folding assembly, tRNA aminoacylation adhesion processes.
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