ArticleProceedings of the National Academy of Sciences of the United States of America2015
Glycosphingolipids are modulators of disease pathogenesis in amyotrophic lateral sclerosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 2 of them syntheses that pooled it.
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Who cites it
90 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.
- A Transcriptomic Meta-Analysis Shows Lipid Metabolism Dysregulation as an Early Pathological Mechanism in the Spinal Cord of SOD1 Mice.International journal of molecular sciences · 2021Pooled it
- Antibody-Based Therapeutic Interventions for Amyotrophic Lateral Sclerosis: A Systematic Literature Review.Frontiers in neuroscience · 2021Pooled it
- A pharmaco-metabolomics approach in a clinical trial of ALS: Identification of predictive markers of progression.PloS one · 2018Trial
- Engineered GM1 Intersects Between Mitochondrial and Synaptic Pathways to Ameliorate ALS Pathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Proteograph™-based proteome and sphingolipidome analyses identified novel serum biomarkers to monitor astronauts' health in spaceflight.Frontiers in physiology · 2026Article
- The Role of the Golgi Apparatus in Neurodegeneration.Sub-cellular biochemistry · 2026Review
- Evaluating the CRP Interactome: Insights into Possible Novel Roles in Cellular Signaling and Tumorigenicity.Current issues in molecular biology · 2025Review
- Review
- Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review).International journal of molecular medicine · 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
- Review
- Myelin Lipid Alterations in Neurodegenerative Diseases: Landscape and Pathogenic Implications.Antioxidants & redox signaling · 2024Review
- Unravelling neuronal and glial differences in ceramide composition, synthesis, and sensitivity to toxicity.Communications biology · 2024Article
- Mechanistic and Therapeutic Implications of Protein and Lipid Sialylation in Human Diseases.International journal of molecular sciences · 2024Review
- The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- Glutamate, Gangliosides, and the Synapse: Electrostatics at Work in the Brain.International journal of molecular sciences · 2024Review
- Glycogen accumulation modulates life span in a mouse model of amyotrophic lateral sclerosis.Journal of neurochemistry · 2024Article
- SPTLC2 variants are associated with early-onset ALS and FTD due to aberrant sphingolipid synthesis.Annals of clinical and translational neurology · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Recent genetic evidence suggests that aberrant glycosphingolipid metabolism plays an important role in several neuromuscular diseases including hereditary spastic paraplegia, hereditary sensory neuropathy type 1, and non-5q spinal muscular atrophy. Here, we investigated whether altered glycosphingolipid metabolism is a modulator of disease course in amyotrophic lateral sclerosis (ALS). Levels of ceramide, glucosylceramide, galactocerebroside, lactosylceramide, globotriaosylceramide, and the gangliosides GM3 and GM1 were significantly elevated in spinal cords of ALS patients. Moreover, enzyme activities (glucocerebrosidase-1, glucocerebrosidase-2, hexosaminidase, galactosylceramidase, α-galactosidase, and β-galactosidase) mediating glycosphingolipid hydrolysis were also elevated up to threefold. Increased ceramide, glucosylceramide, GM3, and hexosaminidase activity were also found in SOD1(G93A) mice, a familial model of ALS. Inhibition of glucosylceramide synthesis accelerated disease course in SOD1(G93A) mice, whereas infusion of exogenous GM3 significantly slowed the onset of paralysis and increased survival. Our results suggest that glycosphingolipids are likely important participants in pathogenesis of ALS and merit further analysis as potential drug targets.
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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.