ArticleOncotarget2016
Patient fibroblasts-derived induced neurons demonstrate autonomous neuronal defects in adult-onset Krabbe disease.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Functional impact of the ATP1A3-p.A813V variant: insights into a calcium-driven hyperexcitability cascade in rapid-onset dystonia-Parkinsonism.Journal of translational medicine · 2026Article
- Very late-onset Krabbe disease with concomitant dementia: case description and a critical review of the literature.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Neuroimmunology in globoid cell leukodystrophy: A comprehensive review including treatments, models, and neuroimmune mechanisms underlying neuropathology.Journal of neuroimmunology · 2025Review
- 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
- Neurodegenerative Disorder Risk in Krabbe Disease Carriers.International journal of molecular sciences · 2022Article
- Neuron-specific ablation of the Krabbe disease gene galactosylceramidase in mice results in neurodegeneration.PLoS biology · 2022Article
- Neurons contribute to pathology in a mouse model of Krabbe disease in a cell-autonomous manner.PLoS biology · 2022Article
- A novel compound heterozygous mutation in GALC associated with adult-onset Krabbe disease: case report and literature review.Neurogenetics · 2022Review
- A neglected neurodegenerative disease: Adult-onset globoid cell leukodystrophy.Frontiers in neuroscience · 2022Review
- Adult-onset Krabbe disease presenting with progressive myoclonic epilepsy and asymmetric occipital lesions: A case report.Frontiers in neurology · 2022Article
- Human iPSC-derived astrocytes generated from donors with globoid cell leukodystrophy display phenotypes associated with disease.PloS one · 2022Article
- The application of in vitro-derived human neurons in neurodegenerative disease modeling.Journal of neuroscience research · 2021Review
- Dietary Antioxidants and the Mitochondrial Quality Control: Their Potential Roles in Parkinson's Disease Treatment.Antioxidants (Basel, Switzerland) · 2020Review
- Adult-onset Krabbe disease due to a homozygous GALC mutation without abnormal signals on an MRI in a consanguineous family: A case report.Molecular genetics & genomic medicine · 2020Article
- Generation of inner ear hair cells by direct lineage conversion of primary somatic cells.eLife · 2020Article
- Pathogenic Variants inFrontiers in neurology · 2020Article
- GALC mutations in Chinese patients with late-onset Krabbe disease: a case report.BMC neurology · 2019Article
- Quantitative Microproteomics Based Characterization of the Central and Peripheral Nervous System of a Mouse Model of Krabbe Disease.Molecular & cellular proteomics : MCP · 2019Article
- The Second Case of Saposin A Deficiency and Altered Autophagy.JIMD reports · 2019Article
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14 authors at 9 institutions in 4 countries.
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Abstract
Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by defective β-galactosylceramidase (GALC), a lysosomal enzyme responsible for cleavage of several key substrates including psychosine. Accumulation of psychosine to the cytotoxic levels in KD patients is thought to cause dysfunctions in myelinating glial cells based on a comprehensive study of demyelination in KD. However, recent evidence suggests myelin-independent neuronal death in the murine model of KD, thus indicating defective GALC in neurons as an autonomous mechanism for neuronal cell death in KD. These observations prompted us to generate induced neurons (iNeurons) from two adult-onset KD patients carrying compound heterozygous mutations (p.[K563*];[L634S]) and (p.[N228_S232delinsTP];[G286D]) to determine the direct contribution of autonomous neuronal toxicity to KD. Here we report that directly converted KD iNeurons showed not only diminished GALC activity and increased psychosine levels, as expected, but also neurite fragmentation and abnormal neuritic branching. The lysosomal-associated membrane proteins 1 (LAMP1) was expressed at higher levels than controls, LAMP1-positive vesicles were significantly enlarged and fragmented, and mitochondrial morphology and its function were altered in KD iNeurons. Strikingly, we demonstrated that psychosine was sufficient to induce neurite defects, mitochondrial fragmentation, and lysosomal alterations in iNeurons derived in healthy individuals, thus establishing the causal effect of the cytotoxic GALC substrate in KD and the autonomous neuronal toxicity in KD pathology.
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