ArticleJournal of human genetics2018
Unfolded protein response is activated in Krabbe disease in a manner dependent on the mutation type.
Article in Journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 23 citations in OpenAlex.
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Identifying altered developmental pathways in human globoid cell leukodystrophy iPSCs-derived NSCs using transcriptome profiling.BMC genomics · 2023Article
- Generation and characterization of motor neuron progenitors and motor neurons using metachromatic leukodystrophy-induced pluripotent stem cells.Molecular genetics and metabolism reports · 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
- Review
- Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes.Stem cell reports · 2021Article
- Sphingolipid lysosomal storage diseases: from bench to bedside.Lipids in health and disease · 2021Review
- NPC1 silent variant induces skipping of exon 11 (p.V562V) and unfolded protein response was found in a specific Niemann-Pick type C patient.Molecular genetics & genomic medicine · 2020Article
- Lysosomal Storage Disorders Shed Light on Lysosomal Dysfunction in Parkinson's Disease.International journal of molecular sciences · 2020Review
- A Novel Homozygous Missense Variant in the NAGA Gene with Extreme Intrafamilial Phenotypic Heterogeneity.Journal of molecular neuroscience : MN · 2020Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Krabbe disease, one of the autosomal-recessive lysosomal storage disorders (LSDs), is caused by a deficiency of galactocerebrosidase (GALC) activity, resulting in the intracellular accumulation of psychosine, which is cytotoxic for neuronal cells. Genetically pathogenic mutations result in conformational changes in GALC and disrupt the lysosmal trafficking of cargos, which subsequently accumulate in the endoplasmic reticulum (ER). Recently, ER stress together with the activation of the unfolded protein response (UPR) has been suggested to play a key role in the pathogenesis of LSDs. In this study, we hence investigated whether the UPR is activated in Krabbe disease using COS-7 cells expressing pathogenic GALC mutants and skin fibroblasts (SFs) from Krabbe disease patients with various phenotypes, using a combination of semiquantitative and quantitative real-time polymerase chain reactions. We found that UPR activation in Krabbe disease depends on the mutations and cell types, and there is the possibility that multiple pathways, involving ER chaperones, inositol-requiring kinase 1, and protein kinase regulated by RNA-like ER kinase are activated by mutations associated with the infantile form. These results indicate that in Krabbe disease, each misfolded/unfolded protein evokes different UPR activation depending on the mutation, and that the activated pathways affect the phenotypes.
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