ArticleThe Journal of biological chemistry2011
Side chain-oxidized oxysterols regulate the brain renin-angiotensin system through a liver X receptor-dependent mechanism.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- Trial
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Loss of the liver circadian clock affects the expression of intrarenal renin-angiotensin system components.Scientific reports · 2025Article
- Phospholipids, Sphingolipids, and Cholesterol-Derived Lipid Mediators and Their Role in Neurological Disorders.International journal of molecular sciences · 2024Review
- CYP46A1-mediated cholesterol turnover induces sex-specific changes in cognition and counteracts memory loss in ovariectomized mice.Science advances · 2024Article
- Alzheimer's disease biomarker profiling in a memory clinic cohort without common comorbidities.Brain communications · 2023Article
- Ventriculoperitoneal Shunt Treatment Increases 7 Alpha Hy-Droxy-3-Oxo-4-Cholestenoic Acid and 24-Hydroxycholesterol Concentrations in Idiopathic Normal Pressure Hydrocephalus.Brain sciences · 2022Article
- Differential proteomic analysis of mouse cerebrums with high-fat diet (HFD)-induced hyperlipidemia.PeerJ · 2022Article
- Hypercholesterolemia and 27-Hydroxycholesterol Increase S100A8 and RAGE Expression in the Brain: a Link Between Cholesterol, Alarmins, and Neurodegeneration.Molecular neurobiology · 2021Article
- Cholesterol Dysmetabolism in Alzheimer's Disease: A Starring Role for Astrocytes?Antioxidants (Basel, Switzerland) · 2021Review
- Sex difference in flux of 27-hydroxycholesterol into the brain.British journal of pharmacology · 2021Article
- The Controversial Role of 24-S-Hydroxycholesterol in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Cholesterol Metabolism in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.Molecular neurobiology · 2021Review
- A Crosstalk Between Brain Cholesterol Oxidation and Glucose Metabolism in Alzheimer's Disease.Frontiers in neuroscience · 2019Review
- 27-Hydroxycholesterol Induces Aberrant Morphology and Synaptic Dysfunction in Hippocampal Neurons.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- Drugs and Scaffold That Inhibit Cytochrome P450 27A1 In Vitro and In Vivo.Molecular pharmacology · 2018Article
- Toward common mechanisms for risk factors in Alzheimer's syndrome.Alzheimer's & dementia (New York, N. Y.) · 2017Review
- 27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation.The Journal of experimental medicine · 2017Article
- Apolipoprotein E4 Elicits Lysosomal Cathepsin D Release, Decreased Thioredoxin-1 Levels, and Apoptosis.Journal of Alzheimer's disease : JAD · 2017Article
- A High-Cholesterol Diet Increases 27-Hydroxycholesterol and Modifies Estrogen Receptor Expression and Neurodegeneration in Rabbit Hippocampus.Journal of Alzheimer's disease : JAD · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Disturbances in cholesterol metabolism have been associated with hypertension and neurodegenerative disorders. Because cholesterol metabolism in the brain is efficiently separated from plasma cholesterol by the blood-brain barrier (BBB), it is an unsolved paradox how high blood cholesterol can cause an effect in the brain. Here, we discuss the possibility that cholesterol metabolites permeable to the BBB might account for these effects. We show that 27-hydroxycholesterol (27-OH) and 24S-hydroxycholesterol (24S-OH) up-regulate the renin-angiotensin system (RAS) in the brain. Brains of mice on a cholesterol-enriched diet showed up-regulated angiotensin converting enzyme (ACE), angiotensinogen (AGT), and increased JAK/STAT activity. These effects were confirmed in in vitro studies with primary neurons and astrocytes exposed to 27-OH or 24S-OH, and were partially mediated by liver X receptors. In contrast, brain RAS activity was decreased in Cyp27a1-deficient mice, a model exhibiting reduced 27-OH production from cholesterol. Moreover, in humans, normocholesterolemic patients with elevated 27-OH levels, due to a CYP7B1 mutation, had markers of activated RAS in their cerebrospinal fluid. Our results demonstrate that side chain-oxidized oxysterols are modulators of brain RAS. Considering that levels of cholesterol and 27-OH correlate in the circulation and 27-OH can pass the BBB into the brain, we suggest that this cholesterol metabolite could be a link between high plasma cholesterol levels, hypertension, and neurodegeneration.
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