ArticleEnvironmental health perspectives2020
Screening ToxCast™ for Chemicals That Affect Cholesterol Biosynthesis: Studies in Cell Culture and Human Induced Pluripotent Stem Cell-Derived Neuroprogenitors.
Article in Environmental health perspectives, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Chemical Inhibition of Sterol Biosynthesis.Biomolecules · 2024Pooled it
- Embryotoxicity of pyrethroid insecticides and their mixtures in a human induced pluripotent stem cell-based model in vitro.Archives of toxicology · 2026Article
- Sterol biosynthesis, brain development, and disease.The Journal of clinical investigation · 2026Review
- Deficiency of Toll-like receptor 2 is a driver of sex-related compositional and structural rearrangements of membrane lipids.Communications chemistry · 2025Article
- Post-lanosterol inhibition profile based classification of commonly used prescription medications.Translational psychiatry · 2025Article
- Inhibition of post-lanosterol biosynthesis by fentanyl: potential implications for Fetal Fentanyl Syndrome (FFS).Molecular psychiatry · 2024Article
- The exposome and liver disease - how environmental factors affect liver health.Journal of hepatology · 2023Review
- Synergistic Activity of Ketoconazole and Miconazole with Prochloraz in Inducing Oxidative Stress, GSH Depletion, Mitochondrial Dysfunction, and Apoptosis in Mouse Sertoli TM4 Cells.International journal of molecular sciences · 2022Article
- Medication effects on developmental sterol biosynthesis.Molecular psychiatry · 2022Review
- Genome-wide expression screening in the cardiac embryonic stem cell test shows additional differentiation routes that are regulated by morpholines and piperidines.Current research in toxicology · 2022Article
- Building a Network of Adverse Outcome Pathways (AOPs) Incorporating the Tau-Driven AOP Toward Memory Loss (AOP429).Journal of Alzheimer's disease reports · 2022Review
- Sterol Biosynthesis Inhibition in Pregnant Women Taking Prescription Medications.ACS pharmacology & translational science · 2021Article
- Prescription Medications Alter Neuronal and Glial Cholesterol Synthesis.ACS chemical neuroscience · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundChanges in cholesterol metabolism are common hallmarks of neurodevelopmental pathologies. A diverse array of genetic disorders of cholesterol metabolism support this claim as do multiple lines of research that demonstrate chemical inhibition of cholesterol biosynthesis compromises neurodevelopment. Recent work has revealed that a number of commonly used pharmaceuticals induce changes in cholesterol metabolism that are similar to changes induced by genetic disorders with devastating neurodevelopmental deficiencies.
objectivesWe tested the hypothesis that common environmental toxicants may also impair cholesterol metabolism and thereby possibly contribute to neurodevelopmental toxicity.
methodsUsing high-throughput screening with a targeted lipidomic analysis and the mouse neuroblastoma cell line, Neuro-2a, the ToxCast™ chemical library was screened for compounds that impact sterol metabolism. Validation of chemical effects was conducted by assessing cholesterol biosynthesis in human induced pluripotent stem cell (hiPSC)-derived neuroprogenitors using an isotopically labeled cholesterol precursor and by monitoring product formation with UPLC-MS/MS.
resultsTwenty-nine compounds were identified as validated lead-hits, and four were prioritized for further study (endosulfan sulfate, tributyltin chloride, fenpropimorph, and spiroxamine). All four compounds were validated to cause hypocholesterolemia in Neuro-2a cells. The morpholine-like fungicides, fenpropimorph and spiroxamine, mirrored their Neuro-2a activity in four immortalized human cell lines and in a human neuroprogenitor model derived from hiPSCs, but endosulfan sulfate and tributyltin chloride did not.
conclusionsThese data reveal the existence of environmental compounds that interrupt cholesterol biosynthesis and that methodologically hiPSC neuroprogenitor cells provide a particularly sensitive system to monitor the effect of small molecules on
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