ArticleProceedings of the National Academy of Sciences of the United States of America2016
Endogenous B-ring oxysterols inhibit the Hedgehog component Smoothened in a manner distinct from cyclopamine or side-chain oxysterols.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 61 citations in OpenAlex.
- Sterol biosynthesis, brain development, and disease.The Journal of clinical investigation · 2026Review
- Article
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- Smith-Lemli-Opitz syndrome: A pathophysiological manifestation of the Bloch hypothesis.Frontiers in molecular biosciences · 2023Review
- Article
- 7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome.eLife · 2022Article
- Triterpenoids as Reactive Oxygen Species Modulators of Cell Fate.Chemical research in toxicology · 2022Review
- Sterol regulation of developmental and oncogenic Hedgehog signaling.Biochemical pharmacology · 2022Review
- The Intimate Connection Between Lipids and Hedgehog Signaling.Frontiers in cell and developmental biology · 2022Review
- Δ9-Tetrahydrocannabinol inhibits Hedgehog-dependent patterning during development.Development (Cambridge, England) · 2021Article
- Cholesterol metabolism pathways - are the intermediates more important than the products?The FEBS journal · 2021Review
- Auditory phenotype of Smith-Lemli-Opitz syndrome.American journal of medical genetics. Part A · 2021Article
- Prescription Medications Alter Neuronal and Glial Cholesterol Synthesis.ACS chemical neuroscience · 2021Article
- Bile acid biosynthesis in Smith-Lemli-Opitz syndrome bypassing cholesterol: Potential importance of pathway intermediates.The Journal of steroid biochemistry and molecular biology · 2021Article
- Sterol and oxysterol synthases near the ciliary base activate the Hedgehog pathway.The Journal of cell biology · 2021Article
- Oxysterols as lipid mediators: Their biosynthetic genes, enzymes and metabolites.Prostaglandins & other lipid mediators · 2020Review
- Article
- Sonic hedgehog signaling in epithelial tissue development.Regenerative medicine research · 2019Article
- Cilia-Associated Oxysterols Activate Smoothened.Molecular cell · 2018Article
- An update on oxysterol biochemistry: New discoveries in lipidomics.Biochemical and biophysical research communications · 2018Review
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Cellular lipids are speculated to act as key intermediates in Hedgehog signal transduction, but their precise identity and function remain enigmatic. In an effort to identify such lipids, we pursued a Hedgehog pathway inhibitory activity that is particularly abundant in flagellar lipids of Chlamydomonas reinhardtii, resulting in the purification and identification of ergosterol endoperoxide, a B-ring oxysterol. A mammalian analog of ergosterol, 7-dehydrocholesterol (7-DHC), accumulates in Smith-Lemli-Opitz syndrome, a human genetic disease that phenocopies deficient Hedgehog signaling and is caused by genetic loss of 7-DHC reductase. We found that depleting endogenous 7-DHC with methyl-β-cyclodextrin treatment enhances Hedgehog activation by a pathway agonist. Conversely, exogenous addition of 3β,5α-dihydroxycholest-7-en-6-one, a naturally occurring B-ring oxysterol derived from 7-DHC that also accumulates in Smith-Lemli-Opitz syndrome, blocked Hedgehog signaling by inhibiting activation of the essential transduction component Smoothened, through a mechanism distinct from Smoothened modulation by other lipids.
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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.