ArticleNature communications2016
25-hydroxycholesterol contributes to cerebral inflammation of X-linked adrenoleukodystrophy through activation of the NLRP3 inflammasome.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 161 citations in OpenAlex.
- PPARγ Signaling in the Central Nervous System: A Review of the Implications in Synaptic Plasticity, Neuroinflammatory and Neoplastic Processes.Neurochemical research · 2026Review
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- NCOA4 Accelerates Abdominal Aortic Aneurysm Formation by Regulating Macrophage Activation and Ferroptosis via STAT1-CH25H Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The complex lipidome as a driver of tissue-specific pathology in adrenoleukodystrophy.Molecular neurodegeneration · 2026Review
- Microglial-Derived Cholesterol 25-Hydroxylase Promotes Epileptic Seizure and Neuroinflammation Mediated by NLRP3 Inflammasome and Lipid Metabolism.Neuroscience bulletin · 2026Article
- Oxysterol signaling in the central nervous system: cellular mechanisms and implications for neurodegeneration.Frontiers in molecular neuroscience · 2026Review
- Peroxisomal ABCD1 deficiency in mice drives Th1 bias through 25-HC-LXR signaling in CD4Frontiers in immunology · 2026Article
- The forgotten inflammasomes: AIM2, NLRP1, and NLRC4 in spinal cord injury and neuroinflammation.Inflammopharmacology · 2025Review
- An AAV-Based Therapy Approach for Neurological Phenotypes of X-Linked Adrenoleukodystrophy.International journal of molecular sciences · 2025Review
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Silencing of Cholesterol 25-Hydroxylase Attenuates Lipopolysaccharide-Induced Cardiomyocyte Damage In Vitro.Journal of cellular and molecular medicine · 2025Article
- Toxoplasma gondii-induced host's high secretion of 25-hydroxycholesterol for immunoprotection.Parasites & vectors · 2025Article
- Liver X Receptor Activation Alleviates Hepatic Ischemia-Reperfusion Injury in Diabetes by Inhibiting NF-κB-NLRP3 Activation.Immunity, inflammation and disease · 2025Article
- Oxysterol-Induced Inflammation in Human Diseases: Strategies for Treatment with Natural Compounds and Synthetic Molecules.Molecules (Basel, Switzerland) · 2025Review
- Effects of acute pro-inflammatory stimulation and 25-hydroxycholesterol on hippocampal plasticity and learning involve NLRP3 inflammasome and cellular stress responses.Scientific reports · 2025Article
- A Novel Mouse Model for Cerebral Inflammatory Demyelination in X-Linked Adrenoleukodystrophy: Insights into Pathogenesis and Potential Therapeutic Targets.Annals of neurology · 2025Article
- Microglial NLRP3-gasdermin D activation impairs blood-brain barrier integrity through interleukin-1β-independent neutrophil chemotaxis upon peripheral inflammation in mice.Nature communications · 2025Article
- Transcriptomic analysis of identical twins with different onset ages of adrenoleukodystrophy.Frontiers in neuroscience · 2025Article
- Peroxisomes as emerging clinical targets in neuroinflammatory diseases.Frontiers in molecular neuroscience · 2025Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
X-linked adrenoleukodystrophy (X-ALD), caused by an ABCD1 mutation, is a progressive neurodegenerative disorder associated with the accumulation of very long-chain fatty acids (VLCFA). Cerebral inflammatory demyelination is the major feature of childhood cerebral ALD (CCALD), the most severe form of ALD, but its underlying mechanism remains poorly understood. Here, we identify the aberrant production of cholesterol 25-hydroxylase (CH25H) and 25-hydroxycholesterol (25-HC) in the cellular context of CCALD based on the analysis of ALD patient-derived induced pluripotent stem cells and ex vivo fibroblasts. Intriguingly, 25-HC, but not VLCFA, promotes robust NLRP3 inflammasome assembly and activation via potassium efflux-, mitochondrial reactive oxygen species (ROS)- and liver X receptor (LXR)-mediated pathways. Furthermore, stereotaxic injection of 25-HC into the corpus callosum of mouse brains induces microglial recruitment, interleukin-1β production, and oligodendrocyte cell death in an NLRP3 inflammasome-dependent manner. Collectively, our results indicate that 25-HC mediates the neuroinflammation of X-ALD via activation of the NLRP3 inflammasome.
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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.