ReviewAntioxidants (Basel, Switzerland)2021
The Controversial Role of 24-S-Hydroxycholesterol in Alzheimer's Disease.
Review in Antioxidants (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 67 citations in OpenAlex.
- Dalzanemdor (SAGE-718), a novel, investigational N-methyl-D-aspartate receptor positive allosteric modulator: Safety, tolerability, and clinical pharmacology in randomized dose-finding studies in healthy participants and an open-label study in participants with Huntington's disease.Clinical and translational science · 2024Trial
- Neuronal and Astrocytic Lipid Metabolic Coupling Mediates Ozone-Induced Learning and Memory Impairment.Environment & health (Washington, D.C.) · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Gut microbiota-dependent 24-hydroxycholesterol metabolism contributes to capsaicin-induced amelioration of Alzheimer's disease-like pathology in mice.Nature communications · 2026Article
- Oxysterol signaling in the central nervous system: cellular mechanisms and implications for neurodegeneration.Frontiers in molecular neuroscience · 2026Review
- Emerging insights of bile acids in cardiovascular physiology and disease: from molecular mechanisms to therapeutic potential.Frontiers in pharmacology · 2026Review
- 27-Hydroxycholesterol triggers microglial senescence subsequent to iron over-loading contributes to brain aging, suppressed by Deferoxamine.npj aging · 2025Article
- Identifying Oxysterols Associated With Age and Diet in Mice Using Optimized Reversed-phase Liquid Chromatography-Mass Spectrometry (RPLC-MS).Journal of separation science · 2025Article
- Oxysterol-Induced Inflammation in Human Diseases: Strategies for Treatment with Natural Compounds and Synthetic Molecules.Molecules (Basel, Switzerland) · 2025Review
- Development of Calcium-Dependent Phospholipase A2 Inhibitors to Target Cellular Senescence and Oxidative Stress in Neurodegenerative Diseases.Antioxidants & redox signaling · 2024Review
- Apolipoprotein B gene expression and regulation in relation to Alzheimer's disease pathophysiology.Journal of lipid research · 2024Article
- The early diagnosis of Alzheimer's disease: Blood-based panel biomarker discovery by proteomics and metabolomics.CNS neuroscience & therapeutics · 2024Review
- Calycosin-7-O-β-D-Glucoside Ameliorates Palmitate-Induced Lipid Accumulation in HT22 Cells.Actas espanolas de psiquiatria · 2024Article
- Plasma oxysterols are associated with serum lipids and dementia risk in older women.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Article
- Latest advances on new promising molecular-based therapeutic approaches for Huntington's disease.Journal of translational internal medicine · 2024Article
- Novel insights into brain lipid metabolism in Alzheimer's disease: Oligodendrocytes and white matter abnormalities.FEBS open bio · 2024Review
- CYP46A1-mediated cholesterol turnover induces sex-specific changes in cognition and counteracts memory loss in ovariectomized mice.Science advances · 2024Article
- Implication of Oxysterols and Phytosterols in Aging and Human Diseases.Advances in experimental medicine and biology · 2024Review
- Oxysterols as Biomarkers of Aging and Disease.Advances in experimental medicine and biology · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The development of Alzheimer's disease (AD) is influenced by several events, among which the dysregulation of cholesterol metabolism in the brain plays a major role. Maintenance of brain cholesterol homeostasis is essential for neuronal functioning and brain development. To maintain the steady-state level, excess brain cholesterol is converted into the more hydrophilic metabolite 24-S-hydroxycholesterol (24-OHC), also called cerebrosterol, by the neuron-specific enzyme CYP46A1. A growing bulk of evidence suggests that cholesterol oxidation products, named oxysterols, are the link connecting altered cholesterol metabolism to AD. It has been shown that the levels of some oxysterols, including 27-hydroxycholesterol, 7β-hydroxycholesterol and 7-ketocholesterol, significantly increase in AD brains contributing to disease progression. In contrast, 24-OHC levels decrease, likely due to neuronal loss. Among the different brain oxysterols, 24-OHC is certainly the one whose role is most controversial. It is the dominant oxysterol in the brain and evidence shows that it represents a signaling molecule of great importance for brain function. However, numerous studies highlighted the potential role of 24-OHC in favoring AD development, since it promotes neuroinflammation, amyloid β (Aβ) peptide production, oxidative stress and cell death. In parallel, 24-OHC has been shown to exert several beneficial effects against AD progression, such as preventing tau hyperphosphorylation and Aβ production. In this review we focus on the current knowledge of the controversial role of 24-OHC in AD pathogenesis, reporting a detailed overview of the findings about its levels in different AD biological samples and its noxious or neuroprotective effects in the brain. Given the relevant role of 24-OHC in AD pathophysiology, its targeting could be useful for disease prevention or slowing down its progression.
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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 Socratic graph.