ArticleProceedings of the National Academy of Sciences of the United States of America2011
Insights into Krabbe disease from structures of galactocerebrosidase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- GALC variants affect galactosylceramidase enzymatic activity and risk of Parkinson's disease.Brain : a journal of neurology · 2023Pooled it
- Sphingolipidoses: expanding the spectrum of α-synucleinopathies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Prosaposin in CNS health and disease, metabolic stress and exercise adaptation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- PLGA-Encapsulated Cross-Linked GALC Aggregates as a Hierarchical Nanostructured Platform for Enzyme Stabilization and Delivery.International journal of biomaterials · 2026Article
- Molecular Dynamics Simulations of 4Computational and structural biotechnology journal · 2026Article
- Abnormal Splicing ofBiomedicines · 2025Article
- Genetic and Clinical Characteristics of Chinese Adult Patients With Krabbe Disease.CNS neuroscience & therapeutics · 2025Article
- Molecular Characterization of the GALC Mutation Thr112Ala Causing Krabbe Disease.International journal of molecular sciences · 2025Article
- Investigating the Cellular Effects of GALC Dosing in Enzyme Replacement Therapy for Krabbe Disease Supports the Role of Nanomedicine.Advanced biology · 2025Article
- Article
- Neuroimmunology in globoid cell leukodystrophy: A comprehensive review including treatments, models, and neuroimmune mechanisms underlying neuropathology.Journal of neuroimmunology · 2025Review
- High Prevalence of GALC Gene Variants in Adults With Neurodegenerative Conditions.European journal of neurology · 2025Article
- Linking glycosphingolipid metabolism to disease-related changes in the plasma membrane proteome.Biochemical Society transactions · 2024Review
- Late-onset Krabbe disease presenting as spastic paraplegia - implications of GCase and CTSB/D.Annals of clinical and translational neurology · 2024Article
- GBA1 inactivation in oligodendrocytes affects myelination and induces neurodegenerative hallmarks and lipid dyshomeostasis in mice.Molecular neurodegeneration · 2024Article
- Structural dissection of two redox proteins from the shipworm symbiont Teredinibacter turnerae.IUCrJ · 2024Article
- Galactosylceramidase deficiency and pathological abnormalities in cerebral white matter of Krabbe disease.Neurobiology of disease · 2022Article
- 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
- A neglected neurodegenerative disease: Adult-onset globoid cell leukodystrophy.Frontiers in neuroscience · 2022Review
- Review
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8 authors at 2 institutions in 1 country.
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Abstract
Krabbe disease is a devastating neurodegenerative disease characterized by widespread demyelination that is caused by defects in the enzyme galactocerebrosidase (GALC). Disease-causing mutations have been identified throughout the GALC gene. However, a molecular understanding of the effect of these mutations has been hampered by the lack of structural data for this enzyme. Here we present the crystal structures of GALC and the GALC-product complex, revealing a novel domain architecture with a previously uncharacterized lectin domain not observed in other hydrolases. All three domains of GALC contribute residues to the substrate-binding pocket, and disease-causing mutations are widely distributed throughout the protein. Our structures provide an essential insight into the diverse effects of pathogenic mutations on GALC function in human Krabbe variants and a compelling explanation for the severity of many mutations associated with fatal infantile disease. The localization of disease-associated mutations in the structure of GALC will facilitate identification of those patients that would be responsive to pharmacological chaperone therapies. Furthermore, our structure provides the atomic framework for the design of such drugs.
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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.