ArticlePloS one2012
Systemic delivery of a glucosylceramide synthase inhibitor reduces CNS substrates and increases lifespan in a mouse model of type 2 Gaucher disease.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Value of Glucosylsphingosine (Lyso-Gb1) as a Biomarker in Gaucher Disease: A Systematic Literature Review.International journal of molecular sciences · 2020Pooled it
- Suppression of Glucosylceramide Synthase Reverses Drug Resistance in Cancer Cells Harboring Homozygous p53 Mutants.International journal of molecular sciences · 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
- Galactokinase 1 is the source of elevated galactose-1-phosphate and cerebrosides are modestly reduced in a mouse model of classic galactosemia.JIMD reports · 2024Article
- Animal Models for the Study of Gaucher Disease.International journal of molecular sciences · 2023Review
- Acid ceramidase involved in pathogenic cascade leading to accumulation of α-synuclein in iPSC model of GBA1-associated Parkinson's disease.Human molecular genetics · 2023Article
- Antiviral activity of glucosylceramide synthase inhibitors in alphavirus infection of the central nervous system.Brain communications · 2023Article
- Dysregulated DNA methylation in the pathogenesis of Fabry disease.Molecular genetics and metabolism reports · 2022Article
- Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine.Translational neurodegeneration · 2022Review
- Precision Medicine in Parkinson's Disease: From Genetic Risk Signals to Personalized Therapy.Brain sciences · 2022Review
- Microglia orchestrate neuroinflammation.eLife · 2022Article
- Article
- Thirty-year clinical outcomes after haematopoietic stem cell transplantation in neuronopathic Gaucher disease.Orphanet journal of rare diseases · 2022Observational
- Glucosylceramide synthase inhibition protects against cardiac hypertrophy in chronic kidney disease.Scientific reports · 2022Article
- Anti-microRNA-21 Therapy on Top of ACE Inhibition Delays Renal Failure in Alport Syndrome Mouse Models.Cells · 2022Article
- Glucosylceramide synthase inhibition reduces ganglioside GM3 accumulation, alleviates amyloid neuropathology, and stabilizes remote contextual memory in a mouse model of Alzheimer's disease.Alzheimer's research & therapy · 2022Article
- A new brain-penetrant glucosylceramide synthase inhibitor as potential Therapeutics for Gaucher disease.Journal of neurochemistry · 2021Article
- Preclinical pharmacology of glucosylceramide synthase inhibitor venglustat in a GBA-related synucleinopathy model.Scientific reports · 2021Article
- Article
- β-Glucosylceramide From Allergic Mothers Enhances Offspring Responsiveness to Allergen.Frontiers in allergy · 2021Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuropathic Gaucher disease (nGD), also known as type 2 or type 3 Gaucher disease, is caused by a deficiency of the enzyme glucocerebrosidase (GC). This deficiency impairs the degradation of glucosylceramide (GluCer) and glucosylsphingosine (GluSph), leading to their accumulation in the brains of patients and mouse models of the disease. These accumulated substrates have been thought to cause the severe neuropathology and early death observed in patients with nGD and mouse models. Substrate accumulation is evident at birth in both nGD mouse models and humans affected with the most severe type of the disease. Current treatment of non-nGD relies on the intravenous delivery of recombinant human glucocerebrosidase to replace the missing enzyme or the administration of glucosylceramide synthase inhibitors to attenuate GluCer production. However, the currently approved drugs that use these mechanisms do not cross the blood brain barrier, and thus are not expected to provide a benefit for the neurological complications in nGD patients. Here we report the successful reduction of substrate accumulation and CNS pathology together with a significant increase in lifespan after systemic administration of a novel glucosylceramide synthase inhibitor to a mouse model of nGD. To our knowledge this is the first compound shown to cross the blood brain barrier and reduce substrates in this animal model while significantly enhancing its lifespan. These results reinforce the concept that systemically administered glucosylceramide synthase inhibitors could hold enhanced therapeutic promise for patients afflicted with neuropathic lysosomal storage diseases.
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