ArticlePloS one2017
Acid sphingomyelinase deficiency enhances myelin repair after acute and chronic demyelination.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- The Cell-Specific Effects of the Human Remyelination-Promoting rHIgM22 on Sphingolipid Metabolism in Cultured Glial Cells.Neurochemical research · 2026Article
- How do different cell populations orchestrate myelin regeneration?Biochemical Society transactions · 2025Review
- Sphingomyelin Inhibits Hydrolytic Activity of Heterodimeric PLAThe Journal of membrane biology · 2025Article
- Lysophosphatidylcholine induces ceramide synthase-2 expression in primary culture model of astrocytopathy: potential therapeutic target in multiple sclerosis.Molecular biology reports · 2025Article
- Impact of calcitriol and PGDDrug delivery and translational research · 2024Article
- NEMO-Binding Domain/IKKγ Inhibitory Peptide Alleviates Neuronal Pyroptosis in Spinal Cord Injury by Inhibiting ASMase-Induced Lysosome Membrane Permeabilization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Nutritional roles and therapeutic potentials of dietary sphingomyelin in brain diseases.Journal of clinical biochemistry and nutrition · 2024Article
- Spinal muscular atrophy-like phenotype in a mouse model of acid ceramidase deficiency.Communications biology · 2023Article
- Remyelination in Multiple Sclerosis: Findings in the Cuprizone Model.International journal of molecular sciences · 2022Review
- Myelin repair in Alzheimer's disease: a review of biological pathways and potential therapeutics.Translational neurodegeneration · 2022Review
- Fingolimod effects on the brain are mediated through biochemical modulation of bioenergetics, autophagy, and neuroinflammatory networks.Proteomics · 2022Article
- Therapeutic effect of combination vitamin D3 and siponimod on remyelination and modulate microglia activation in cuprizone mouse model of multiple sclerosis.Frontiers in behavioral neuroscience · 2022Article
- Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain-Barré syndrome.Scientific reports · 2020Article
- Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinase in vitro.Journal of lipid research · 2020Article
- Review
- Neuroprotective Effects of Melatonin during Demyelination and Remyelination Stages in a Mouse Model of Multiple Sclerosis.Journal of molecular neuroscience : MN · 2020Article
- Multiple Sclerosis: Melatonin, Orexin, and Ceramide Interact with Platelet Activation Coagulation Factors and Gut-Microbiome-Derived Butyrate in the Circadian Dysregulation of Mitochondria in Glia and Immune Cells.International journal of molecular sciences · 2019Review
- Human Remyelination Promoting Antibody Stimulates Astrocytes Proliferation Through Modulation of the Sphingolipid Rheostat in Primary Rat Mixed Glial Cultures.Neurochemical research · 2019Article
- Choline and choline-related nutrients in regular and preterm infant growth.European journal of nutrition · 2019Review
- Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy.The Journal of clinical investigation · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cuprizone animal model, also known as the toxic demyelination model, is a well-reproducible model of demyelination- and remyelination in mice, and has been useful in studying important aspect of human demyelinating diseases, including multiple sclerosis. In this study, we investigated the role of acid sphingomyelinase in demyelination and myelin repair by inducing acute and chronic demyelination with 5- or 12-week cuprizone treatment, followed by a 2-week cuprizone withdrawal phase to allow myelin repair. Sphingolipids, in particular ceramide and the enzyme acid sphingomyelinase, which generates ceramide from sphingomyelin, seem to be involved in astrocyte activation and neuronal damage in multiple sclerosis. We used immunohistochemistry to study glial reaction and oligodendrocyte distribution in acid sphingomyelinase deficient mice and wild-type C57BL/6J littermates at various time intervals after demyelination and remyelination. Axonal injury was quantified using amyloid precursor protein and synaptophysin, and gene expression and protein levels were measured using gene analysis and Western blotting, respectively. Our results show that mice lacking acid sphingomyelinase had a significant increase in myelin recovery and a significantly higher oligodendrocyte cell count after 2 weeks remyelination compared to wild-type littermates. Detrimental astroglial distribution was also significantly reduced in acid sphingomyelinase deficient animals. We obtained similar results in experiments using amitriptyline to inhibit acid sphingomyelinase. These findings suggest that acid sphingomyelinase plays a significant role in myelin repair, and its inhibition by amitriptyline may constitute a novel therapeutic approach for multiple sclerosis patients.
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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.