ArticleThe Journal of clinical investigation2023
Accumulation of α-synuclein mediates podocyte injury in Fabry nephropathy.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Fabry disease cardiomyopathy: A state-of-the-art review.Progress in cardiovascular diseasesPooled it
- Development and validation of a self-management efficacy questionnaire for patients with Fabry disease in China.Annals of medicine · 2026Article
- Pathophysiological mechanisms of organ injury in Fabry disease: Update via multi-omics.Genes & diseases · 2026Review
- Peroxisomal interactome mapping enables network-based modelling of function and disease.Life science alliance · 2026Article
- Neuroimmune Regulation of NLRP3 Signalling in Parkinson's Disease.Molecular neurobiology · 2026Review
- Modeling Fabry nephropathy: insights from experimental systems towards precision nephrology.Disease models & mechanisms · 2026Review
- Sphingolipidoses: expanding the spectrum of α-synucleinopathies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Expert Opinion on the Conceptual, Clinical, and Therapeutic Aspects of Fabry Nephropathy: A Nephrologists' Perspective.Kidney & blood pressure research · 2026Review
- Impaired glycolysis-derived serine metabolism as a key driver of podocyte injury with senescence.Nature communications · 2025Article
- Review
- Mechanisms and Therapeutic Perspectives of Podocyte Aging in Podocytopathies.International journal of molecular sciences · 2025Review
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- Status and frontiers of Fabre disease.Orphanet journal of rare diseases · 2025Review
- Lectin-Based Substrate Detection in Fabry Disease Using the Gb3-Binding Lectins StxB and LecA.International journal of molecular sciences · 2025Article
- CerS6 links ceramide metabolism to innate immune responses in diabetic kidney disease.Nature communications · 2025Article
- Fabry Disease Podocytes Reveal Ferroptosis as a Potential Regulator of Cell Pathology.Kidney international reports · 2025Article
- Brain-derived extracellular vesicles potentially mediate crosstalk with peripheral organs in neurodegenerative diseases.Frontiers in cell and developmental biology · 2025Review
- Human sensory-like neuron surfaceome analysis.PloS one · 2025Article
- Overcoming Resistance in Anderson-Fabry Disease: Current Therapeutic Challenges and Future Perspectives.Journal of clinical medicine · 2024Article
- Human in vitro models for Fabry disease: new paths for unravelling disease mechanisms and therapies.Journal of translational medicine · 2024Review
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Authors and funding
38 authors at 7 institutions in 8 countries.
Funding
Abstract
Current therapies for Fabry disease are based on reversing intracellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization of the defective enzyme, thereby alleviating lysosomal dysfunction. However, their effect in the reversal of end-organ damage, like kidney injury and chronic kidney disease, remains unclear. In this study, ultrastructural analysis of serial human kidney biopsies showed that long-term use of ERT reduced Gb3 accumulation in podocytes but did not reverse podocyte injury. Then, a CRISPR/Cas9-mediated α-galactosidase knockout podocyte cell line confirmed ERT-mediated reversal of Gb3 accumulation without resolution of lysosomal dysfunction. Transcriptome-based connectivity mapping and SILAC-based quantitative proteomics identified α-synuclein (SNCA) accumulation as a key event mediating podocyte injury. Genetic and pharmacological inhibition of SNCA improved lysosomal structure and function in Fabry podocytes, exceeding the benefits of ERT. Together, this work reconceptualizes Fabry-associated cell injury beyond Gb3 accumulation, and introduces SNCA modulation as a potential intervention, especially for patients with Fabry nephropathy.
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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.