ArticleTraffic (Copenhagen, Denmark)2016
Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants.
Article in Traffic (Copenhagen, Denmark), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Establishing gene regulatory networks from Parkinson's disease risk loci.Brain : a journal of neurology · 2022Pooled it
- 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
- Genetic and Clinical Characteristics of Chinese Adult Patients With Krabbe Disease.CNS neuroscience & therapeutics · 2025Article
- The molecular landscape of hereditary ataxia: a single-center study.Human genetics · 2025Article
- Article
- A novel mutation in the GALC gene causes Krabbe disease accompanied with extensive Mongolian spots in a consanguineous family.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Article
- Altered plasma membrane abundance of the sulfatide-binding protein NF155 links glycosphingolipid imbalances to demyelination.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Galactosylceramidase deficiency and pathological abnormalities in cerebral white matter of Krabbe disease.Neurobiology of disease · 2022Article
- Ceramide/Sphingosine 1-Phosphate Axis as a Key Target for Diagnosis and Treatment in Alzheimer's Disease and Other Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- CRISPR-Cas9 Knock-In of T513M and G41S Mutations in the Murine β-Galactosyl-Ceramidase Gene Re-capitulates Early-Onset and Adult-Onset Forms of Krabbe Disease.Frontiers in molecular neuroscience · 2022Article
- Advances in the Diagnosis and Treatment of Krabbe Disease.International journal of neonatal screening · 2021Review
- Ceramide Metabolism and Parkinson's Disease-Therapeutic Targets.Biomolecules · 2021Review
- Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes.Stem cell reports · 2021Article
- Low Psychosine in Krabbe Disease with Onset in Late Infancy: A Case Report.International journal of neonatal screening · 2021Article
- The Bicyclic Form ofACS medicinal chemistry letters · 2021Article
- Molecular Biomarkers in Multiple Sclerosis and Its Related Disorders: A Critical Review.International journal of molecular sciences · 2020Review
- Pathogenic Variants inFrontiers in neurology · 2020Article
- Advances in Sphingolipidoses: CRISPR-Cas9 Editing as an Option for Modelling and Therapy.International journal of molecular sciences · 2019Review
- Large-scale functional LIPA variant characterization to improve birth prevalence estimates of lysosomal acid lipase deficiency.Human mutation · 2019Article
- Unfolded protein response is activated in Krabbe disease in a manner dependent on the mutation type.Journal of human genetics · 2018Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 4 countries.
Funding
Abstract
Krabbe disease is a severe, fatal neurodegenerative disorder caused by defects in the lysosomal enzyme galactocerebrosidase (GALC). The correct targeting of GALC to the lysosome is essential for the degradation of glycosphingolipids including the primary lipid component of myelin. Over 100 different mutations have been identified in GALC that cause Krabbe disease but the mechanisms by which they cause disease remain unclear. We have generated monoclonal antibodies against full-length human GALC and used these to monitor the trafficking and processing of GALC variants in cell-based assays and by immunofluorescence microscopy. Striking differences in the secretion, processing and endosomal targeting of GALC variants allows the classification of these into distinct categories. A subset of GALC variants are not secreted by cells, not proteolytically processed, and remain trapped in the ER; these are likely to cause disease due to protein misfolding and should be targeted for pharmacological chaperone therapies. Other GALC variants can be correctly secreted by cells and cause disease due to catalytic defects in the enzyme active site, inappropriate post-translational modification or a potential inability to bind essential cofactors. The classification of disease pathogenesis presented here provides a molecular framework for appropriate targeting of future Krabbe disease therapies.
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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.