ArticleGlia2013
MMP-3 mediates psychosine-induced globoid cell formation: implications for leukodystrophy pathology.
Article in Glia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Thoracic surgery for spontaneous pneumothorax in a long-term survivor of infantile Krabbe disease: a case report.Journal of cardiothoracic surgery · 2026Article
- Neuroimmunology in globoid cell leukodystrophy: A comprehensive review including treatments, models, and neuroimmune mechanisms underlying neuropathology.Journal of neuroimmunology · 2025Review
- Amelioration of Inflammation and Metabolic Blockage in GALC Deficient Mice After Enzyme Replacement Therapy via Extracellular Vesicles.International journal of nanomedicine · 2025Article
- Ablation of lipocalin-2 reduces neuroinflammation in a mouse model of Krabbe disease.Scientific reports · 2024Article
- Human iPSC-derived myelinating organoids and globoid cells to study Krabbe Disease.bioRxiv : the preprint server for biology · 2024Article
- Perinatal loss of galactosylceramidase in both oligodendrocytes and microglia is crucial for the pathogenesis of Krabbe disease in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Article
- Article
- Human iPSC-derived astrocytes generated from donors with globoid cell leukodystrophy display phenotypes associated with disease.PloS one · 2022Article
- Review
- Krabbe disease: New hope for an old disease.Neuroscience letters · 2021Review
- Genetic defects in the sphingolipid degradation pathway and their effects on microglia in neurodegenerative disease.Cellular signalling · 2021Review
- Krabbe Disease: Prospects of Finding a Cure Using AAV Gene Therapy.Frontiers in medicine · 2021Review
- The Role of Microglia in Inherited White-Matter Disorders and Connections to Frontotemporal Dementia.The application of clinical genetics · 2021Review
- Deregulation of signalling in genetic conditions affecting the lysosomal metabolism of cholesterol and galactosyl-sphingolipids.Neurobiology of disease · 2020Review
- Fingolimod Rescues Demyelination in a Mouse Model of Krabbe's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage.The Journal of clinical investigation · 2017Article
- Lysosomal Re-acidification Prevents Lysosphingolipid-Induced Lysosomal Impairment and Cellular Toxicity.PLoS biology · 2016Article
- Neuroimmune mechanisms in Krabbe's disease.Journal of neuroscience research · 2016Review
- Port-to-port delivery: Mobilization of toxic sphingolipids via extracellular vesicles.Journal of neuroscience research · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Globoid cell leukodystrophy (GLD) or Krabbe disease, is a fatal demyelinating disease attributed to mutations in the galactocerebrosidase (GALC) gene. Loss of function mutations in GALC result in accumulation of the glycolipid intermediate, galactosylsphingosine (psychosine). Due to the cytotoxicity of psychosine, it has been hypothesized that accumulated psychosine underlie the pathophysiology of GLD. However, the cellular mechanisms of GLD pathophysiology remain unclear. Globoid cells, multinucleated microglia/macrophages in the central nervous system (CNS), are a defining characteristic of GLD. Here we report that exposure of primary glial cultures to psychosine induces the expression and the production of matrix metalloproteinase (MMP)-3 that mediated a morphological transformation of microglia into a multinucleated globoid cell type. Additionally, psychosine-induced globoid cell formation from microglia was prevented by either genetic ablation or chemical inhibition of MMP-3. These effects are microglia-specific as peripheral macrophages exposed to psychosine did not become activated or express increased levels of MMP-3. In the brain from twitcher mice, a murine model of human GLD, elevated MMP-3 expression relative to wild-type littermates was contemporaneous with disease onset and further increased with disease progression. Further, bone marrow transplantation (BMT), currently the only therapeutically beneficial treatment for GLD, did not mitigate the elevated expression of MMP-3 in twitcher mice. Hence, elevated expression of MMP-3 in GLD may promote microglial responses to psychosine that may represent an important pathophysiological process in this disease and its treatment.
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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.