ArticleJournal of human genetics2015
Chaperone therapy for Krabbe disease: potential for late-onset GALC mutations.
Article in Journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- Molecular Dynamics Simulations of 4Computational and structural biotechnology journal · 2026Article
- 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
- Second-Generation Pharmacological Chaperones: Beyond Inhibitors.Molecules (Basel, Switzerland) · 2020Review
- Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses.International journal of molecular sciences · 2019Review
- Future clinical and biochemical predictions of Fabry disease in females by methylation studies of theMolecular genetics and metabolism reports · 2019Article
- Unfolded protein response is activated in Krabbe disease in a manner dependent on the mutation type.Journal of human genetics · 2018Article
- Heterozygous carriers of galactocerebrosidase mutations that cause Krabbe disease have impaired microglial function and defective repair of myelin damage.Neural regeneration research · 2018Review
- Emptying the stores: lysosomal diseases and therapeutic strategies.Nature reviews. Drug discovery · 2018Review
- Pharmaceutical Chaperones and Proteostasis Regulators in the Therapy of Lysosomal Storage Disorders: Current Perspective and Future Promises.Frontiers in pharmacology · 2017Review
- Quantum dots and potential therapy for Krabbe's disease.Journal of neuroscience research · 2016Review
- New therapeutic approaches for Krabbe disease: The potential of pharmacological chaperones.Journal of neuroscience research · 2016Review
- Biochemical, cell biological, pathological, and therapeutic aspects of Krabbe's disease.Journal of neuroscience research · 2016Review
- Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants.Traffic (Copenhagen, Denmark) · 2016Article
- Altered Trafficking and Processing of GALC Mutants Correlates with Globoid Cell Leukodystrophy Severity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Endoplasmic Reticulum Protein Quality Control Failure in Myelin Disorders.Frontiers in molecular neuroscience · 2016Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Krabbe disease is an autosomal recessive leukodystrophy caused by a deficiency of the galactocerebrosidase (GALC) enzyme. Hematopoietic stem cells transplantation is the only available treatment option for pre-symptomatic patients. We have previously reported the chaperone effect of N-octyl-4-epi-β-valienamine (NOEV) on mutant GM1 β-galactosidase proteins, and in a murine GM1-gangliosidosis model. In this study, we examined its chaperone effect on mutant GALC proteins. We found that NOEV strongly inhibited GALC activity in cell lysates of GALC-transfected COS1 cells. In vitro NOEV treatment stabilized GALC activity under heat denaturation conditions. We also examined the effect of NOEV on cultured COS1 cells expressing mutant GALC activity and human skin fibroblasts from Krabbe disease patients: NOEV significantly increased the enzyme activity of mutants of late-onset forms. Moreover, we confirmed that NOEV could enhance the maturation of GALC precursor to its mature active form. Model structural analysis showed NOEV binds to the active site of human GALC protein. These results, for the first time, provide clear evidence that NOEV is a chaperone with promising potential for patients with Krabbe disease resulting from the late-onset mutations.
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