ArticleThe Journal of experimental medicine2024
Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 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
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Viral Mimicry of Alzheimer's Disease: Innate Sensing of Self-Nucleic Acids as a Driver of Glial Senescence.Journal of molecular neuroscience : MN · 2026Review
- Targeting CH25H/25HC-ferroptosis axis: a novel mechanism of MSC-EVs mediated renoprotection in ischemic AKI.Journal of nanobiotechnology · 2026Article
- Oxysterol signaling in the central nervous system: cellular mechanisms and implications for neurodegeneration.Frontiers in molecular neuroscience · 2026Review
- APOE Lipoprotein Particles: Pathophysiology, Therapy, and the Crosstalk in Alzheimer's Disease and Cardiovascular Disease.Molecular neurobiology · 2025Review
- Cell autonomous microglia defects in a stem cell model of frontotemporal dementia tau.Molecular psychiatry · 2025Article
- Lipid and lipoprotein metabolism in microglia: Alzheimer's disease mechanisms and interventions.Journal of lipid research · 2025Review
- The role of 25-hydroxycholesterol in the pathophysiology of brain vessel dysfunction associated with infection and cholesterol dysregulation.Disease models & mechanisms · 2025Article
- Plasma membrane accessible cholesterol is regulated by ACC1 and lipid droplets.bioRxiv : the preprint server for biology · 2025Article
- APOE4 Exacerbates Cerebral Tau Pathology Through Cholesterol-Induced Degradation of Phosphatase in Atherosclerosis.CNS neuroscience & therapeutics · 2025Article
- Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025Review
- 25-Hydroxycholesterol modulates microglial function and exacerbates Alzheimer's disease pathology: mechanistic insights and therapeutic potential of cholesterol esterification inhibition.Journal of neuroinflammation · 2025Article
- Lipidome disruption in Alzheimer's disease brain: detection, pathological mechanisms, and therapeutic implications.Molecular neurodegeneration · 2025Review
- Zika virus induces monocyte recruitment in the immunocompetent adult brain driving chronic inflammation.Frontiers in immunology · 2025Article
- Single-Cell RNA Sequencing Reveals Microglial Heterogeneity and Functional States After Cerebral Ischemia-Reperfusion Injury.Journal of inflammation research · 2025Article
- Increased 25-hydroxycholesterol as an indicator for patients with vestibular neuritis.Frontiers in neurology · 2025Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles, in addition to neuroinflammation and changes in brain lipid metabolism. 25-Hydroxycholesterol (25-HC), a known modulator of both inflammation and lipid metabolism, is produced by cholesterol 25-hydroxylase encoded by Ch25h expressed as a "disease-associated microglia" signature gene. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and the resultant reduction in 25-HC, there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice, which express the P301S mutant human tau transgene. Transcriptomic analyses of bulk hippocampal tissue and single nuclei revealed that Ch25h deficiency in PS19 mice strongly suppressed proinflammatory signaling in microglia. Our results suggest a key role for Ch25h/25-HC in potentiating proinflammatory signaling to promote tau-mediated neurodegeneration. Ch25h may represent a novel therapeutic target for primary tauopathies, AD, and other neuroinflammatory diseases.
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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.