ArticleCell reports. Medicine2023
Tracer metabolomics reveals the role of aldose reductase in glycosylation.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Stress-induced secretory pathway disruption causes atypical metalloproteinase transport in PMM2-CDG.iScience · 2026Article
- Repurposing the HMG-CoA reductase inhibitor atorvastatin for SRD5A3-congenital disorder of glycosylation.Communications medicine · 2026Article
- Targeting POLRMT-driven epigenetic remodeling of Wnt/β-catenin to eradicate colorectal cancer stem cell proliferation.Cell death and differentiation · 2026Article
- Lipo-Glc-1,6-PIUBMB life · 2026Article
- PGM1 deficiency is linked to sarcomeric and mitochondrial dysfunction in patient-derived iPSC-cardiomyocytes.Journal of translational medicine · 2026Article
- Repurposing the HMG-CoA Reductase Inhibitor Atorvastatin for SRD5A3-CDG.bioRxiv : the preprint server for biology · 2026Article
- Article
- Resolving Hexose-Phosphates by LC-MS Leads to New Insights in PGM1-CDG Pathophysiology.ACS omega · 2025Article
- Predicting disease-overarching therapeutic approaches for Congenital Disorders of Glycosylation using multi-OMICS.bioRxiv : the preprint server for biology · 2025Article
- Glycosphingolipid synthesis is impaired in SLC35A2-CDG and improves with galactose supplementation.Cellular and molecular life sciences : CMLS · 2025Article
- Novel mouse model reveals neurodevelopmental origin of PMM2-CDG brain pathology.bioRxiv : the preprint server for biology · 2025Article
- Targeted metabolomic evaluation of peripheral blood mononucleated cells from patients with PMM2-CDG.Scientific reports · 2025Article
- AAV-based gene replacement therapy prevents and halts manifestation of abnormal neurological phenotypes in a novel mouse model of PMM2-CDG.Gene therapy · 2025Article
- Goal attainment in PMM2-CDG: A new approach measuring meaningful clinical outcomes.Molecular genetics and metabolism · 2025Article
- Epalrestat Alleviates Reactive Oxygen Species and Endoplasmic Reticulum Stress by Maintaining Glycosylation in IMS32 Schwann Cells Under Exposure to Galactosemic Conditions.International journal of molecular sciences · 2025Article
- The pathogenesis of diabetic kidney disease and the therapeutic potential of bioactive substances.Frontiers in pharmacology · 2025Review
- O-GlcNAcylation modulates expression and abundance of N-glycosylation machinery in an inherited glycosylation disorder.Cell reports · 2024Article
- Genetics of glycosylation in mammalian development and disease.Nature reviews. Genetics · 2024Review
- Frontiers in congenital disorders of glycosylation consortium, a cross-sectional study report at year 5 of 280 individuals in the natural history cohort.Molecular genetics and metabolism · 2024Article
- AAV9-basedMolecular genetics and metabolism reports · 2024Article
Corrections and comments
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Authors and funding
21 authors at 10 institutions in 4 countries.
Funding
Abstract
Abnormal polyol metabolism is predominantly associated with diabetes, where excess glucose is converted to sorbitol by aldose reductase (AR). Recently, abnormal polyol metabolism has been implicated in phosphomannomutase 2 congenital disorder of glycosylation (PMM2-CDG) and an AR inhibitor, epalrestat, proposed as a potential therapy. Considering that the PMM2 enzyme is not directly involved in polyol metabolism, the increased polyol production and epalrestat's therapeutic mechanism in PMM2-CDG remained elusive. PMM2-CDG, caused by PMM2 deficiency, presents with depleted GDP-mannose and abnormal glycosylation. Here, we show that, apart from glycosylation abnormalities, PMM2 deficiency affects intracellular glucose flux, resulting in polyol increase. Targeting AR with epalrestat decreases polyols and increases GDP-mannose both in patient-derived fibroblasts and in pmm2 mutant zebrafish. Using tracer studies, we demonstrate that AR inhibition diverts glucose flux away from polyol production toward the synthesis of sugar nucleotides, and ultimately glycosylation. Finally, PMM2-CDG individuals treated with epalrestat show a clinical and biochemical improvement.
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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.