ArticleMolecular neurobiology2021
Hypercholesterolemia and 27-Hydroxycholesterol Increase S100A8 and RAGE Expression in the Brain: a Link Between Cholesterol, Alarmins, and Neurodegeneration.
Article in Molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Oxysterol signaling in the central nervous system: cellular mechanisms and implications for neurodegeneration.Frontiers in molecular neuroscience · 2026Review
- Bioenergetics and lipid metabolism in Alzheimer's disease: From cell biology to systemic health.Journal of internal medicine · 2026Review
- Minocycline Ameliorates Cognitive Impairments Without Modulating Microglial Reactivity in Sporadic Hypercholesterolemia: A Sex-Specific Analysis in Mice.Molecular neurobiology · 2025Article
- Reactive Astrocytes with Reduced Function of Glutamate Transporters in theACS chemical neuroscience · 2025Article
- The Effects of Hyperlipidemia on Postoperative Cognitive Dysfunction in Patients Undergoing Laparoscopic Gynecological Tumor Surgery.Neuropsychiatric disease and treatment · 2025Article
- 27-Hydroxycholesterol acts on estrogen receptor α expressed by POMC neurons in the arcuate nucleus to modulate feeding behavior.Science advances · 2024Article
- Impact of high-fat diet on cognitive behavior and central and systemic inflammation with aging and sex differences in mice.Brain, behavior, and immunity · 2024Article
- Impaired astrocytic synaptic function by peripheral cholesterol metabolite 27-hydroxycholesterol.Frontiers in cellular neuroscience · 2024Article
- Reexamining the Causes and Effects of Cholesterol Deposition in the Brains of Patients with Alzheimer's Disease.Molecular neurobiology · 2023Review
- Proteome profiling of hippocampus reveals the neuroprotective effect of mild hypothermia on global cerebral ischemia-reperfusion injury in rats.Scientific reports · 2023Article
- A systematic review for the development of Alzheimer's disease inFrontiers in aging neuroscience · 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
- Connecting the Dots Between Hypercholesterolemia and Alzheimer's Disease: A Potential Mechanism Based on 27-Hydroxycholesterol.Frontiers in neuroscience · 2022Review
- Defects of Nutrient Signaling and Autophagy in Neurodegeneration.Frontiers in cell and developmental biology · 2022Review
- Cholesterol Dysmetabolism in Alzheimer's Disease: A Starring Role for Astrocytes?Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Alterations in cholesterol metabolism in the brain have a major role in the physiology of Alzheimer's disease (AD). Oxysterols are cholesterol metabolites with multiple implications in memory functions and in neurodegeneration. Previous studies have shown detrimental effects of cholesterol metabolites in neurons, but its effect in glial cells is unknown. We used a high-fat/high-cholesterol diet in mice to study the effects of hypercholesterolemia over the alarmin S100A8 cascade in the hippocampus. Using CYP27Tg, a transgenic mouse model, we show that the hypercholesterolemia influence on the brain is mediated by the excess of 27-hydroxycholesterol (27-OH), a cholesterol metabolite. We also employed an acute model of 27-OH intraventricular injection in the brain to study RAGE and S100A8 response. We used primary cultures of neurons and astrocytes to study the effect of high levels of 27-OH over the S100A8 alarmin cascade. We report that a high-fat/high-cholesterol diet leads to an increase in S100A8 production in the brain. In CYP27Tg, we report an increase of S100A8 and its receptor RAGE in the hippocampus under elevated 27-OH in the brain. Using siRNA, we found that 27-OH upregulation of RAGE in astrocytes and neurons is mediated by the nuclear receptor RXRγ. Silencing RXRγ in neurons prevented 27-OH-mediated upregulation of RAGE. These results show that S100A8 alarmin and RAGE respond to high levels of 27-OH in the brain in both neurons and astrocytes through RXRγ. Our study supports the notion that 27-OH mediates detrimental effects of hypercholesterolemia to the brain via alarmin signaling.
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Registered trials
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