ArticleMolecular neurodegeneration2017
Fibroblast bioenergetics to classify amyotrophic lateral sclerosis patients.
Article in Molecular neurodegeneration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Gene expression profiles in sporadic ALS fibroblasts define disease subtypes and the metabolic effects of the investigational drug EH301.Human molecular genetics · 2022Pooled it
- Trial
- Review
- Investigation of mitochondrial phenotypes in motor neurons derived by direct conversion of fibroblasts from familial ALS subjects.Cell death & disease · 2025Article
- Article
- Modulation of Mitochondria-Endoplasmic Reticulum Contacts (MERCs) by Small Molecules as a New Strategy for Restoring Lipid Metabolism in an Amyotrophic Lateral Sclerosis Model.Journal of medicinal chemistry · 2025Article
- Sodium Phenylbutyrate and Tauroursodeoxycholic Acid: A Story of Hope Turned to Disappointment in Amyotrophic Lateral Sclerosis Treatment.Clinical drug investigation · 2024Review
- Mitochondria: A Promising Convergent Target for the Treatment of Amyotrophic Lateral Sclerosis.Cells · 2024Review
- Article
- Time-restricted ketogenic diet in amyotrophic lateral sclerosis: a case study.Frontiers in neurology · 2023Article
- A Y374X TDP43 truncation leads to an altered metabolic profile in amyotrophic lateral sclerosis fibroblasts driven by pyruvate and TCA cycle intermediate alterations.Frontiers in aging neuroscience · 2023Article
- Fatty acids derived from the probiotic Lacticaseibacillus rhamnosus HA-114 suppress age-dependent neurodegeneration.Communications biology · 2022Article
- Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine.Translational neurodegeneration · 2022Review
- Integrative Profiling of Amyotrophic Lateral Sclerosis Lymphoblasts Identifies Unique Metabolic and Mitochondrial Disease Fingerprints.Molecular neurobiology · 2022Article
- Effects of PB-TURSO on the transcriptional and metabolic landscape of sporadic ALS fibroblasts.Annals of clinical and translational neurology · 2022Article
- Targeting phosphoglycerate kinase 1 with terazosin improves motor neuron phenotypes in multiple models of amyotrophic lateral sclerosis.EBioMedicine · 2022Article
- Amyotrophic lateral sclerosis alters the metabolic aging profile in patient derived fibroblasts.Neurobiology of aging · 2021Article
- Storage of Mutant Human SOD1 in Non-Neural Cells from the Type-1 Amyotrophic Lateral Sclerosis ratBiomedicines · 2021Article
- Neuroprotective Potential of Mild Uncoupling in Mitochondria. Pros and Cons.Brain sciences · 2021Review
- Metabolic Abnormalities, Dietary Risk Factors and Nutritional Management in Amyotrophic Lateral Sclerosis.Nutrients · 2021Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundThe objective of this study was to investigate cellular bioenergetics in primary skin fibroblasts derived from patients with amyotrophic lateral sclerosis (ALS) and to determine if they can be used as classifiers for patient stratification.
methodsWe assembled a collection of unprecedented size of fibroblasts from patients with sporadic ALS (sALS, n = 171), primary lateral sclerosis (PLS, n = 34), ALS/PLS with C9orf72 mutations (n = 13), and healthy controls (n = 91). In search for novel ALS classifiers, we performed extensive studies of fibroblast bioenergetics, including mitochondrial membrane potential, respiration, glycolysis, and ATP content. Next, we developed a machine learning approach to determine whether fibroblast bioenergetic features could be used to stratify patients.
resultsCompared to controls, sALS and PLS fibroblasts had higher average mitochondrial membrane potential, respiration, and glycolysis, suggesting that they were in a hypermetabolic state. Only membrane potential was elevated in C9Orf72 lines. ATP steady state levels did not correlate with respiration and glycolysis in sALS and PLS lines. Based on bioenergetic profiles, a support vector machine (SVM) was trained to classify sALS and PLS with 99% specificity and 70% sensitivity.
conclusionssALS, PLS, and C9Orf72 fibroblasts share hypermetabolic features, while presenting differences of bioenergetics. The absence of correlation between energy metabolism activation and ATP levels in sALS and PLS fibroblasts suggests that in these cells hypermetabolism is a mechanism to adapt to energy dissipation. Results from SVM support the use of metabolic characteristics of ALS fibroblasts and multivariate analysis to develop classifiers for patient stratification.
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