ArticleHuman molecular genetics2015
Amyotrophic lateral sclerosis and denervation alter sphingolipids and up-regulate glucosylceramide synthase.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 93 citations in OpenAlex.
- Lipidomics study of plasma from patients suggest that ALS and PLS are part of a continuum of motor neuron disorders.Scientific reports · 2021Trial
- A pharmaco-metabolomics approach in a clinical trial of ALS: Identification of predictive markers of progression.PloS one · 2018Trial
- Sphingolipid Remodeling and Extracellular Vesicle Signatures Reflect Disease Severity in Facioscapulohumeral Dystrophy Driven by Mitochondrial Dysfunction and Endoplasmic Reticulum Stress.Antioxidants (Basel, Switzerland) · 2026Article
- Early and Divergent Lipid Mediator Remodelling in Fast Versus Slow Skeletal Muscles of Female hSOD1Journal of cachexia, sarcopenia and muscle · 2026Article
- Disruption of the angiopoietin-like system connects lipid homeostasis and hypothalamic dysfunction in ALS.BMC medicine · 2026Article
- Proteograph™-based proteome and sphingolipidome analyses identified novel serum biomarkers to monitor astronauts' health in spaceflight.Frontiers in physiology · 2026Article
- Review
- Glycerophospholipids in ALS: insights into disease mechanisms and clinical implication.Molecular neurodegeneration · 2025Review
- Longitudinal Metabolomics in Amyotrophic Lateral Sclerosis Implicates Impaired Lipid Metabolism.Annals of neurology · 2025Article
- Lipid Metabolism and Statin Therapy in Neurodegenerative Diseases: An Endocrine View.Metabolites · 2025Review
- Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.Translational neurodegeneration · 2025Review
- Gangliosides as Therapeutic Targets for Neurodegenerative Diseases.Journal of lipids · 2024Review
- Sphingolipid abnormalities in encephalomyeloradiculoneuropathy (EMRN) are associated with an anti-neutral glycolipid antibody.FEBS open bio · 2023Review
- Ganglioside GM1 and the Central Nervous System.International journal of molecular sciences · 2023Review
- Evidence of Metabolic Dysfunction in Amyotrophic Lateral Sclerosis (ALS) Patients and Animal Models.Biomolecules · 2023Review
- Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration.International journal of molecular sciences · 2023Review
- Involvement of Lipids in the Pathogenesis of Amyotrophic Lateral Sclerosis.Life (Basel, Switzerland) · 2023Review
- Treatment with THI, an inhibitor of sphingosine-1-phosphate lyase, modulates glycosphingolipid metabolism and results therapeutically effective in experimental models of Huntington's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Metabolomics identifies shared lipid pathways in independent amyotrophic lateral sclerosis cohorts.Brain : a journal of neurology · 2022Article
- Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine.Translational neurodegeneration · 2022Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset disease characterized by upper and lower motor neuron degeneration, muscle wasting and paralysis. Growing evidence suggests a link between changes in lipid metabolism and ALS. Here, we used UPLC/TOF-MS to survey the lipidome in SOD1(G86R) mice, a model of ALS. Significant changes in lipid expression were evident in spinal cord and skeletal muscle before overt neuropathology. In silico analysis also revealed appreciable changes in sphingolipids including ceramides and glucosylceramides (GlcCer). HPLC analysis showed increased amounts of GlcCer and downstream glycosphingolipids (GSLs) in SOD1(G86R) muscle compared with wild-type littermates. Glucosylceramide synthase (GCS), the enzyme responsible for GlcCer biosynthesis, was up-regulated in muscle of SOD1(G86R) mice and ALS patients, and in muscle of wild-type mice after surgically induced denervation. Conversely, inhibition of GCS in wild-type mice, following transient peripheral nerve injury, reversed the overexpression of genes in muscle involved in oxidative metabolism and delayed motor recovery. GCS inhibition in SOD1(G86R) mice also affected the expression of metabolic genes and induced a loss of muscle strength and morphological deterioration of the motor endplates. These findings suggest that GSLs may play a critical role in ALS muscle pathology and could lead to the identification of new therapeutic targets.
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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.