ArticleNature medicine2010
Inhibition of glucosylceramide accumulation results in effective blockade of polycystic kidney disease in mouse models.
Article in Nature medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 174 citations in OpenAlex.
- Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Oral Venglustat in Healthy Volunteers.Clinical pharmacology in drug development · 2021Trial
- Metabolic determinants of autoimmune kidney diseases.Nature reviews. Nephrology · 2026Review
- Functional Specialization of Clathrin-Independent Endocytic Routes: Mechanisms and Cellular Roles.Traffic (Copenhagen, Denmark) · 2026Review
- Review
- Ganglioside GM3 in the Tumor Microenvironment: Mechanisms of Signaling Regulation and Strategies for Angiogenesis Inhibition.Biomolecules · 2026Review
- Pellino1-mTOR/S6K1 signaling axis is a key pathogenesis for the development of polycystic kidney disease.Cell death & disease · 2026Article
- Altered glycolipid metabolism during acute kidney injury exacerbates renal inflammation.Scientific reports · 2025Article
- A dual fluorescent-Raman bioorthogonal probe for specific biosynthetic labeling of intracellular gangliosides.Communications chemistry · 2025Article
- Precision genomic profiling in Gaucher disease: insights from atypical presentations.Frontiers in genetics · 2025Article
- Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.Communications biology · 2024Article
- Glucosylceramide flippases contribute to cellular glucosylceramide homeostasis.Journal of lipid research · 2024Article
- Role of UDP-glucose ceramide glucosyltransferase in venous malformation.Frontiers in cell and developmental biology · 2023Article
- Impact of renal tubularFrontiers in molecular biosciences · 2023Article
- Metabolism-based approaches for autosomal dominant polycystic kidney disease.Frontiers in molecular biosciences · 2023Review
- Glucose absorption drives cystogenesis in a human organoid-on-chip model of polycystic kidney disease.Nature communications · 2022Article
- SCF-SKP2 E3 ubiquitin ligase links mTORC1/ER stress/ISR with YAP activation in murine renal cystogenesis.The Journal of clinical investigation · 2022Article
- Parapelvic Cysts: An Imaging Marker of Kidney Disease Potentially Leading to the Diagnosis of Treatable Rare Genetic Disorders? A Narrative Review of the Literature.Journal of nephrology · 2022Review
- The STAGED-PKD 2-Stage Adaptive Study With a Patient Enrichment Strategy and Treatment Effect Modeling for Improved Study Design Efficiency in Patients With ADPKD.Kidney medicine · 2022Article
- The lonidamine derivative H2-gamendazole reduces cyst formation in polycystic kidney disease.American journal of physiology. Renal physiology · 2022Article
- Review
28 more citing papers are in PubMed but not listed here.
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15 authors at 1 institution in 1 country.
Funding
Abstract
Polycystic kidney disease (PKD) represents a family of genetic disorders characterized by renal cystic growth and progression to kidney failure. No treatment is currently available for people with PKD, although possible therapeutic interventions are emerging. Despite genetic and clinical heterogeneity, PKDs have in common defects of cystic epithelia, including increased proliferation, apoptosis and activation of growth regulatory pathways. Sphingolipids and glycosphingolipids are emerging as major regulators of these cellular processes. We sought to evaluate the therapeutic potential for glycosphingolipid modulation as a new approach to treat PKD. Here we demonstrate that kidney glucosylceramide (GlcCer) and ganglioside GM3 levels are higher in human and mouse PKD tissue as compared to normal tissue, regardless of the causative mutation. Blockade of GlcCer accumulation with the GlcCer synthase inhibitor Genz-123346 effectively inhibits cystogenesis in mouse models orthologous to human autosomal dominant PKD (Pkd1 conditional knockout mice) and nephronophthisis (jck and pcy mice). Molecular analysis in vitro and in vivo indicates that Genz-123346 acts through inhibition of the two key pathways dysregulated in PKD: Akt protein kinase-mammalian target of rapamycin signaling and cell cycle machinery. Taken together, our data suggest that inhibition of GlcCer synthesis represents a new and effective treatment option for PKD.
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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.