ArticleEMBO molecular medicine2015
A metabolic switch toward lipid use in glycolytic muscle is an early pathologic event in a mouse model of amyotrophic lateral sclerosis.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
155 citing papers in PubMed, 227 citations in OpenAlex.
- An open-label Phase 2a study to assess the safety and tolerability of trimetazidine in patients with amyotrophic lateral sclerosis.Brain communications · 2025Trial
- Lipidomics study of plasma from patients suggest that ALS and PLS are part of a continuum of motor neuron disorders.Scientific reports · 2021Trial
- Mitochondrial Dynamics and SLC25 Transporters in Neurodegeneration: From Mechanisms to Therapeutic Opportunities.Biomolecules · 2026Review
- Aldh3a1-mediated detoxification of reactive aldehydes contributes to distinct muscle responses to amyotrophic lateral sclerosis progression.Free radical biology & medicine · 2026Article
- Blood Lactate as a Prognostic Biomarker for Survival and Weight Loss in Amyotrophic Lateral Sclerosis: An Exploratory-Validation Study.Annals of neurology · 2026Article
- The hypothalamus is an early site of mitochondrial failure and neuro-immune circuit disruption in amyotrophic lateral sclerosis.Molecular metabolism · 2026Article
- Review of the Pathology of Muscle in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026Review
- Hypothesis-free evaluation of circulating metabolome provides cell-specific insights regarding the role of energy substrate availability in amyotrophic lateral sclerosis.BMC medicine · 2026Article
- Resistance Exercise Counteracts Skeletal Muscle Atrophy in T2DM Mice by Upregulating FGF21 and Activating PI3K/Akt Pathway.Biomolecules · 2025Article
- FABP3 and FABP4 promote lipid peroxidation injury during static cold storage of donor heart: Insights from multi-omics and therapeutic targeting.Journal of molecular and cellular cardiology plus · 2025Article
- Association between Onodera's prognostic nutritional Index and ultrasound-measured muscle thickness in amyotrophic lateral sclerosis: a retrospective cross-sectional study.Annals of medicine · 2025Article
- The role of fatty acids in neurodegenerative diseases: mechanistic insights and therapeutic strategies.Journal of lipid research · 2025Review
- Review
- Surface electrical impedance myography detects disease in an adult-onset SOD1-G93A zebrafish model of amyotrophic lateral sclerosis.Scientific reports · 2025Article
- Integrated molecular data analysis confirms PDK1 as a candidate risk factor in ALS pathophysiology.Molecular brain · 2025Article
- The myokine FGF21 associates with enhanced survival in ALS and mitigates stress-induced cytotoxicity.Aging · 2025Article
- Use of Proteomics to Explore Biomarkers of Amyotrophic Lateral Sclerosis (ALS): Proof of Principle from Humanized SOD1 Mouse to Human ALS.ACS pharmacology & translational science · 2025Review
- Glycerophospholipids in ALS: insights into disease mechanisms and clinical implication.Molecular neurodegeneration · 2025Review
- PDK4 and nutrient responses explain muscle specific manifestation in mitochondrial disease.Clinical and translational medicine · 2025Article
- Exploring the Role of Diabetes in ALS: A Population-Based Cohort Study.Life (Basel, Switzerland) · 2025Article
95 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is the most common fatal motor neuron disease in adults. Numerous studies indicate that ALS is a systemic disease that affects whole body physiology and metabolic homeostasis. Using a mouse model of the disease (SOD1(G86R)), we investigated muscle physiology and motor behavior with respect to muscle metabolic capacity. We found that at 65 days of age, an age described as asymptomatic, SOD1(G86R) mice presented with improved endurance capacity associated with an early inhibition in the capacity for glycolytic muscle to use glucose as a source of energy and a switch in fuel preference toward lipids. Indeed, in glycolytic muscles we showed progressive induction of pyruvate dehydrogenase kinase 4 expression. Phosphofructokinase 1 was inhibited, and the expression of lipid handling molecules was increased. This mechanism represents a chronic pathologic alteration in muscle metabolism that is exacerbated with disease progression. Further, inhibition of pyruvate dehydrogenase kinase 4 activity with dichloroacetate delayed symptom onset while improving mitochondrial dysfunction and ameliorating muscle denervation. In this study, we provide the first molecular basis for the particular sensitivity of glycolytic muscles to ALS pathology.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.