ArticleNeuron2020
Macrophages Expressing GALC Improve Peripheral Krabbe Disease by a Mechanism Independent of Cross-Correction.
Article in Neuron, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Survival benefit and immune-related toxicities after hematopoietic stem cell transplantation in Krabbe disease: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Schwann Cell-Specific ATG7-Dependent Autophagy Protects Myelin in a Mouse Model of Krabbe Disease.Glia · 2026Article
- Characterization of hematopoietic stem cell-derived microglia-like cells in nonhuman primates.Blood advances · 2026Article
- Sphingolipid-neutralizing molecular therapy reduces psychosine cytotoxicity in Krabbe disease.iScience · 2026Article
- Clinical and molecular characterization of Krabbe disease in Iranian patients: case report and literature review.BMC neurology · 2026Review
- Impaired docking and recycling of synaptic vesicles in inherited lysosomal sphingolipidoses.Cell communication and signaling : CCS · 2025Article
- Chimeric enzymes enhance treatment potential for globoid cell leukodystrophy through hematopoietic stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Noncovalent crown ether-assisted separation of stereoisomeric glycosphingosines using cyclic ion mobility spectrometry.Analytical and bioanalytical chemistry · 2025Article
- Molecular Characterization of the GALC Mutation Thr112Ala Causing Krabbe Disease.International journal of molecular sciences · 2025Article
- Metachromatic Leukodystrophy: New Therapy Advancements and Emerging Research Directions.Neurology · 2025Review
- Neuroimmunology in globoid cell leukodystrophy: A comprehensive review including treatments, models, and neuroimmune mechanisms underlying neuropathology.Journal of neuroimmunology · 2025Review
- Direct microglia replacement reveals pathologic and therapeutic contributions of brain macrophages to a monogenic neurological disease.Immunity · 2025Article
- 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
- Cellular trafficking and fate mapping of cells within the nervous system after in utero hematopoietic cell transplantation.Communications biology · 2024Article
- 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
- Genetic and Functional Analyses of Patients with Marked Hypo-High-Density Lipoprotein Cholesterolemia.Journal of atherosclerosis and thrombosis · 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
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
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17 authors at 6 institutions in 1 country.
Funding
Abstract
Many therapies for lysosomal storage disorders rely on cross-correction of lysosomal enzymes. In globoid cell leukodystrophy (GLD), mutations in GALC cause psychosine accumulation, inducing demyelination, a neuroinflammatory "globoid" reaction and neurodegeneration. The efficiency of GALC cross-correction in vivo, the role of the GALC substrate galactosylceramide, and the origin of psychosine are poorly understood. Using a novel GLD model, we show that cross-correction does not occur efficiently in vivo and that Galc-deficient Schwann cells autonomously produce psychosine. Furthermore, macrophages require GALC to degrade myelin, as Galc-deficient macrophages are transformed into globoid cells by exposure to galactosylceramide and produce a more severe GLD phenotype. Finally, hematopoietic stem cell transplantation in patients reduces globoid cells in nerves, suggesting that the phagocytic response of healthy macrophages, rather than cross-correction, contributes to the therapeutic effect. Thus, GLD may be caused by at least two mechanisms: psychosine-induced demyelination and secondary neuroinflammation from galactosylceramide storage in macrophages.
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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.