ArticleHuman molecular genetics2014
Neuronal accumulation of glucosylceramide in a mouse model of neuronopathic Gaucher disease leads to neurodegeneration.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
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Who cites it
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 154 citations in OpenAlex.
- Sphingolipids in Gaucher disease: a systematic review.Orphanet journal of rare diseases · 2025Pooled it
- Value of Glucosylsphingosine (Lyso-Gb1) as a Biomarker in Gaucher Disease: A Systematic Literature Review.International journal of molecular sciences · 2020Pooled it
- Novel Insight in Idiopathic Normal Pressure Hydrocephalus (iNPH) Biomarker Discovery in CSF.International journal of molecular sciences · 2021Trial
- Sphingolipid Remodeling and Extracellular Vesicle Signatures Reflect Disease Severity in Facioscapulohumeral Dystrophy Driven by Mitochondrial Dysfunction and Endoplasmic Reticulum Stress.Antioxidants (Basel, Switzerland) · 2026Article
- Article
- ASAH2 deficiency affects sphingolipid homeostasis and neuromotor control, causing a progressive neurological disorder.HGG advances · 2026Article
- Alterations in secondary lipids are associated with neuroinflammation in the brain of Neu1-deficient mice.Cell and tissue research · 2026Article
- Inhibition or genetic reduction of ASAH1/acid ceramidase restore α-synuclein clearance in mutant GBA1 dopamine neurons from Parkinson's patients.Human molecular genetics · 2025Article
- Central Roles of Glucosylceramide in Driving Cancer Pathogenesis.International journal of molecular sciences · 2025Review
- Review
- Gba1 E326K renders motor and non-motor symptoms with pathological α-synuclein, tau and glial activation.Brain : a journal of neurology · 2024Article
- Glucocerebrosidase deficiency leads to neuropathology via cellular immune activation.PLoS genetics · 2024Article
- Old disease-New reflections: Gaucher, immunity, and inflammation.Journal of cellular and molecular medicine · 2024Review
- Functional Analysis of HumanCells · 2024Article
- Article
- Forward-predictive SERS-based chemical taxonomy for untargeted structural elucidation of epimeric cerebrosides.Nature communications · 2024Article
- GBA1 inactivation in oligodendrocytes affects myelination and induces neurodegenerative hallmarks and lipid dyshomeostasis in mice.Molecular neurodegeneration · 2024Article
- Large-scale proteomics analysis of five brain regions from Parkinson's disease patients with a GBA1 mutation.NPJ Parkinson's disease · 2024Article
- Lysophagy protects against propagation of α-synuclein aggregation through ruptured lysosomal vesicles.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach.International journal of biological sciences · 2024Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Gaucher disease has recently received wide attention due to the unexpected discovery that it is a genetic risk factor for Parkinson's disease. Gaucher disease is caused by the defective activity of the lysosomal enzyme, glucocerebrosidase (GCase; GBA1), resulting in intracellular accumulation of the glycosphingolipids, glucosylceramide and psychosine. The rare neuronopathic forms of GD (nGD) are characterized by profound neurological impairment and neuronal cell death. We have previously described the progression of neuropathological changes in a mouse model of nGD. We now examine the relationship between glycosphingolipid accumulation and initiation of pathology at two pre-symptomatic stages of the disease in four different brain areas which display differential degrees of susceptibility to GCase deficiency. Liquid chromatography electrospray ionization tandem mass spectrometry demonstrated glucosylceramide and psychosine accumulation in nGD brains prior to the appearance of neuroinflammation, although only glucosylceramide accumulation correlated with neuroinflammation and neuron loss. Levels of other sphingolipids, including the pro-apoptotic lipid, ceramide, were mostly unaltered. Transmission electron microscopy revealed that glucosylceramide accumulation occurs in neurons, mostly in the form of membrane-delimited pseudo-tubules located near the nucleus. Highly disrupted glucosylceramide-storing cells, which are likely degenerating neurons containing massive inclusions, numerous autophagosomes and unique ultrastructural features, were also observed. Together, our results indicate that a certain level of neuronal glucosylceramide storage is required to trigger neuropathological changes in affected brain areas, while other brain areas containing similar glucosylceramide levels are unaltered, presumably because of intrinsic differences in neuronal properties, or in the neuronal environment, between various brain regions.
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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.