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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.

The dental school arose from the premise that a dental school would round out the university and add prestige to the burgeoning Health Professions Division with its five schools and eight health programs. The school was founded in light of the following circumstances. Patient Pool Evaluation of community facilities and services revealed that there was an increasing patient pool, without disturbing the present mix. There was evidence of a need for dental care for large numbers of unserved or underserved people. Financial Considerations Proforma and cash flow budget projections showed financial stability of this project. The university was recognized to have the ability to absorb initial capital costs. HPD had a history of the success in functioning with tuition-dependent budgets. University Factors The university has had success in establishing and operating five health professions schools. A complete and experienced infrastructure has existed for sixteen years in the University and in the Health Professions Division. The university would provide unconditional administrative support.

The dental school arose from the premise that a dental school would round out the university and add prestige to the burgeoning Health Professions Division with its five schools and eight health programs. The school was founded in light of the following circumstances. Patient Pool Evaluation of community facilities and services revealed that there was an increasing patient pool, without disturbing the present mix. There was evidence of a need for dental care for large numbers of unserved or underserved people. Financial Considerations Proforma and cash flow budget projections showed financial stability of this project. The university was recognized to have the ability to absorb initial capital costs. HPD had a history of the success in functioning with tuition-dependent budgets. University Factors The university has had success in establishing and operating five health professions schools. A complete and experienced infrastructure has existed for sixteen years in the University and in the Health Professions Division. The university would provide unconditional administrative support.