ArticlePloS one2017
Psychosine enhances the shedding of membrane microvesicles: Implications in demyelination in Krabbe's disease.
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 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- Schwann Cell-Specific ATG7-Dependent Autophagy Protects Myelin in a Mouse Model of Krabbe Disease.Glia · 2026Article
- Unveiling Lipid Dysregulation: Lipidomics of Mouse Brain and Isolated Myelin in Niemann-Pick Disease Type C1.bioRxiv : the preprint server for biology · 2026Article
- Soft-interfaced liquid crystal microfluidics can probe the rigidity of lipid vesicles.Communications materials · 2026Article
- Neuroimmunology in globoid cell leukodystrophy: A comprehensive review including treatments, models, and neuroimmune mechanisms underlying neuropathology.Journal of neuroimmunology · 2025Review
- Linking glycosphingolipid metabolism to disease-related changes in the plasma membrane proteome.Biochemical Society transactions · 2024Review
- Deficiency of galactosyl-ceramidase in adult oligodendrocytes worsens disease severity during chronic experimental allergic encephalomyelitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Dietary Supplementation with n-3 Polyunsaturated Fatty Acids Delays the Phenotypic Manifestation of Krabbe Disease and Partially Restores Lipid Mediator Production in the Brain-Study in a Mouse Model of the Disease.International journal of molecular sciences · 2024Article
- Untargeted Lipidomic Approach for Studying Different Nervous System Tissues of the Murine Model of Krabbe Disease.Biomolecules · 2023Article
- Article
- Preclinical studies in Krabbe disease: A model for the investigation of novel combination therapies for lysosomal storage diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Neuron-specific ablation of the Krabbe disease gene galactosylceramidase in mice results in neurodegeneration.PLoS biology · 2022Article
- Efficacy and Safety of a Krabbe Disease Gene Therapy.Human gene therapy · 2022Article
- Lipidomic analysis identifies age-disease-related changes and potential new biomarkers in brain-derived extracellular vesicles from metachromatic leukodystrophy mice.Lipids in health and disease · 2022Article
- A kaleidoscopic view of extracellular vesicles in lysosomal storage disorders.Extracellular vesicles and circulating nucleic acids · 2022Review
- Insights into Lewy body disease from rare neurometabolic disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Krabbe disease: New hope for an old disease.Neuroscience letters · 2021Review
- Krabbe Disease: Prospects of Finding a Cure Using AAV Gene Therapy.Frontiers in medicine · 2021Review
- Synaptic Function and Dysfunction in Lysosomal Storage Diseases.Frontiers in cellular neuroscience · 2021Article
- Fatty Acid Binding Protein 5 Mediates Cell Death by Psychosine Exposure through Mitochondrial Macropores Formation in Oligodendrocytes.Biomedicines · 2020Article
- Deregulation of signalling in genetic conditions affecting the lysosomal metabolism of cholesterol and galactosyl-sphingolipids.Neurobiology of disease · 2020Review
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
In prior studies, our laboratory showed that psychosine accumulates and disrupts lipid rafts in brain membranes of Krabbe's disease. A model of lipid raft disruption helped explaining psychosine's effects on several signaling pathways important for oligodendrocyte survival and differentiation but provided more limited insight in how this sphingolipid caused demyelination. Here, we have studied how this cationic inverted coned lipid affects the fluidity, stability and structure of myelin and plasma membranes. Using a combination of cutting-edge imaging techniques in non-myelinating (red blood cell), and myelinating (oligodendrocyte) cell models, we show that psychosine is sufficient to disrupt sphingomyelin-enriched domains, increases the rigidity of localized areas in the plasma membrane, and promotes the shedding of membranous microvesicles. The same physicochemical and structural changes were measured in myelin membranes purified from the mutant mouse Twitcher, a model for Krabbe's disease. Areas of higher rigidity were measured in Twitcher myelin and correlated with higher levels of psychosine and of myelin microvesiculation. These results expand our previous analyses and support, for the first time a pathogenic mechanism where psychosine's toxicity in Krabbe disease involves deregulation of cell signaling not only by disruption of membrane rafts, but also by direct local destabilization and fragmentation of the membrane through microvesiculation. This model of membrane disruption may be fundamental to introduce focal weak points in the myelin sheath, and consequent diffuse demyelination in this leukodystrophy, with possible commonality to other demyelinating disorders.
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