ArticleJournal of neuroinflammation2020
25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 114 citations in OpenAlex.
- Article
- NCOA4 Accelerates Abdominal Aortic Aneurysm Formation by Regulating Macrophage Activation and Ferroptosis via STAT1-CH25H Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mass Spectrometry-Based Screening Reveals Inhibitors of Cholesterol 25-Hydroxylase.ACS chemical biology · 2026Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Multi-functionalized chitosan-Extracellular vesicles nanohybrid system for intranasal delivery of pApoE2 to attenuate age-related inflammation.International journal of biological macromolecules · 2026Article
- Lipidomic and sterolomic profiles of different brain regions in the mouse model of Alzheimer's disease.Neural regeneration research · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Structure-activity relationships of steroid and sterol neuromodulators on inflammatory markers in a murine microglial cell line.The Journal of steroid biochemistry and molecular biology · 2026Article
- Molecular mechanisms of exercise-induced improvements in Alzheimer's disease: a focus on lipid homeostasis.Translational neurodegeneration · 2026Review
- Gut microbiota-dependent 24-hydroxycholesterol metabolism contributes to capsaicin-induced amelioration of Alzheimer's disease-like pathology in mice.Nature communications · 2026Article
- Dynamic regulatory mechanism of cholesterol 25-hydroxylase-mediated antiviral response in RNA virus infections.Frontiers in cellular and infection microbiology · 2026Review
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- APOE Lipoprotein Particles: Pathophysiology, Therapy, and the Crosstalk in Alzheimer's Disease and Cardiovascular Disease.Molecular neurobiology · 2025Review
- Lipid and lipoprotein metabolism in microglia: Alzheimer's disease mechanisms and interventions.Journal of lipid research · 2025Review
- Nicotine Attenuates Pathogenesis of Parkinson's Disease via α7-nAChR-Mediated Lipid Metabolic Reprogramming and Anti-inflammatory Signaling.Molecular neurobiology · 2025Article
- Ferroptosis-related hub genes and immune cell dynamics as diagnostic biomarkers in age-related macular degeneration.European journal of medical research · 2025Article
- Toxoplasma gondii-induced host's high secretion of 25-hydroxycholesterol for immunoprotection.Parasites & vectors · 2025Article
- The APOE-Microglia Axis in Alzheimer's Disease: Functional Divergence and Therapeutic Perspectives-A Narrative Review.Brain sciences · 2025Review
- Mechanistic Role of Astrocytic Rac1 Protein in Alzheimer's Disease.Aging and disease · 2025Review
- Sleep Deprivation and Alzheimer's Disease: A Review of the Bidirectional Interactions and Therapeutic Potential of Omega-3.Brain sciences · 2025Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundGenome-wide association studies of Alzheimer's disease (AD) have implicated pathways related to lipid homeostasis and innate immunity in AD pathophysiology. However, the exact cellular and chemical mediators of neuroinflammation in AD remain poorly understood. The oxysterol 25-hydroxycholesterol (25-HC) is an important immunomodulator produced by peripheral macrophages with wide-ranging effects on cell signaling and innate immunity. Cholesterol 25-hydroxylase (CH25H), the enzyme responsible for 25-HC production, has also been found to be one of the disease-associated microglial (DAM) genes that are upregulated in the brain of AD and AD transgenic mouse models.
methodsWe used real-time PCR and immunoblotting to examine CH25H expression in human AD brain tissue and in transgenic mouse brain tissue-bearing amyloid-β plaques or tau pathology. The innate immune response of primary mouse microglia under different treatment conditions or bearing different genetic backgrounds was analyzed using ELISA, western blotting, or immunocytochemistry.
resultsWe found that CH25H expression is upregulated in human AD brain tissue and in transgenic mouse brain tissue-bearing amyloid-β plaques or tau pathology. Treatment with the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) markedly upregulates CH25H expression in the mouse brain and stimulates CH25H expression and 25-HC secretion in mouse primary microglia. We found that LPS-induced microglial production of the pro-inflammatory cytokine IL-1β is markedly potentiated by 25-HC and attenuated by the deletion of CH25H. Microglia expressing apolipoprotein E4 (apoE4), a genetic risk factor for AD, produce greater amounts of 25-HC than apoE3-expressing microglia following treatment with LPS. Remarkably, 25-HC treatment results in a greater level of IL-1β secretion in LPS-activated apoE4-expressing microglia than in apoE2- or apoE3-expressing microglia. Blocking potassium efflux or inhibiting caspase-1 prevents 25-HC-potentiated IL-1β release in apoE4-expressing microglia, indicating the involvement of caspase-1 inflammasome activity.
conclusion25-HC may function as a microglial-secreted inflammatory mediator in the brain, promoting IL-1β-mediated neuroinflammation in an apoE isoform-dependent manner (E4>>E2/E3) and thus may be an important mediator of neuroinflammation in AD.
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