ArticleNature neuroscience2021
Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis.
Article in Nature neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
173 citing papers in PubMed, 1 synthesis or guideline pooled it, 291 citations in OpenAlex.
- Role and Mechanism of Microglia in White Matter Injury Recovery in Ischemic Stroke.Immunity, inflammation and disease · 2025Pooled it
- Lipid droplets as redox-active organelles after spinal cord injury: lipid peroxidation, mitochondrial dysfunction, and neuroinflammation.Redox report : communications in free radical research · 2026Review
- Dynamic metabolic programming of monocyte-derived cells defines immunity in CNS disease.Brain : a journal of neurology · 2026Review
- A Multidimensional Engineering Strategy Reprograms Microglia via Targeted and Sustained-Release Extracellular Vesicles for Spinal Cord Injury Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Foamy microglia link oxylipins to disease progression in multiple sclerosis.Nature neuroscience · 2026Article
- Lipid metabolism, microglia, and stroke.Neural regeneration research · 2026Article
- CTSS regulates macrophage lipid metabolic reprogramming and white matter repair after intracerebral hemorrhage.Journal of translational medicine · 2026Article
- Elevated phagocytic capacity directs innate spinal cord repair.Cell reports · 2026Article
- 18:2 Cholesterol Ester is a Novel Prognostic Biomarker of Disease Progression in Multiple Sclerosis.Molecular neurobiology · 2026Article
- Mitochondrial Targeting of MVA Pathway Triggers Severe Inhibition of Post-Squalene Cholesterol Biosynthesis: Transcriptomic and Proteomic Insights in Yeast.Molecules (Basel, Switzerland) · 2026Article
- Glial cells in chronic inflammation: diversity, dysfunction and therapeutic targeting.Nature reviews. Immunology · 2026Review
- Microglia in systemic neuroimmune communication: functions beyond phagocytosis.Trends in immunology · 2026Review
- CYP46A1-Targeted Treatment Alleviates Long-Term White Matter Injury Following Traumatic Brain Injury by Promoting Cholesterol Metabolic Clearance and Remyelination.CNS neuroscience & therapeutics · 2026Article
- CYP46A1 activation by low-dose efavirenz uncovers the link between brain cholesterol metabolism, energetics, and vasculature.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- The phytosterol 24(S)-saringosterol alters lipid homeostasis and inflammatory pathways in a cell-specific manner.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- ABCA1-mediated lipid efflux restrains oxidative stress and neuroinflammation after spinal cord injury.Journal of neuroinflammation · 2026Article
- Neuregulin-1 facilitates myelin regeneration through microglia-mediated mechanisms in a mouse model of chronic demyelination.Nature communications · 2026Article
- Quantification and Localisation of New Brain Lipid Synthesis Using Deuterium Oxide and High Resolution Mass Spectrometry.Angewandte Chemie (International ed. in English) · 2026Article
- Cognitive Stimulation and Activity-Dependent Myelination: Oligodendroglial Mechanisms Linking Neural Activity and Brain Plasticity.International journal of molecular sciences · 2026Review
113 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 7 institutions in 3 countries.
Funding
Abstract
The repair of inflamed, demyelinated lesions as in multiple sclerosis (MS) necessitates the clearance of cholesterol-rich myelin debris by microglia/macrophages and the switch from a pro-inflammatory to an anti-inflammatory lesion environment. Subsequently, oligodendrocytes increase cholesterol levels as a prerequisite for synthesizing new myelin membranes. We hypothesized that lesion resolution is regulated by the fate of cholesterol from damaged myelin and oligodendroglial sterol synthesis. By integrating gene expression profiling, genetics and comprehensive phenotyping, we found that, paradoxically, sterol synthesis in myelin-phagocytosing microglia/macrophages determines the repair of acutely demyelinated lesions. Rather than producing cholesterol, microglia/macrophages synthesized desmosterol, the immediate cholesterol precursor. Desmosterol activated liver X receptor (LXR) signaling to resolve inflammation, creating a permissive environment for oligodendrocyte differentiation. Moreover, LXR target gene products facilitated the efflux of lipid and cholesterol from lipid-laden microglia/macrophages to support remyelination by oligodendrocytes. Consequently, pharmacological stimulation of sterol synthesis boosted the repair of demyelinated lesions, suggesting novel therapeutic strategies for myelin repair in MS.
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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.