ArticleNature aging2021
Neuronal accumulation of peroxidated lipids promotes demyelination and neurodegeneration through the activation of the microglial NLRP3 inflammasome.
Article in Nature aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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
20 citing papers in PubMed.
- Spatiotemporal disarray of inflammatory microenvironment following spinal cord injury.Neural regeneration research · 2026Article
- The impact of lactate and lipid metabolism in microglia upon cognitive impairment following radiation-induced brain injury.Journal of translational medicine · 2026Review
- Lipid Messengers: Mechanisms and Clinical Applications of Exosomal Lipids in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Histone phosphorylation analysis of two main TCM syndromes of chronic fatigue syndrome.Journal of translational medicine · 2025Article
- Labile iron overload reprograms microglia and neurons for lipid droplet synthesis in the aging brain.bioRxiv : the preprint server for biology · 2025Article
- Spatial lipidomics reveals demyelination and remyelination dynamics in the mouse brain.Journal of lipid research · 2025Article
- Bilirubin Targeting WNK1 to Alleviate NLRP3-Mediated Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Accumulation of Damaging Lipids in the Arf1-Ablated Neurons Promotes Neurodegeneration through Releasing mtDNA and Activating Inflammatory Pathways in Microglia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The circular RNA circbabo(5,6,7,8S) regulates lipid metabolism and neuronal integrity via TGF-β/ROS/JNK/SREBP signaling axis in Drosophila.BMC biology · 2025Article
- Upregulation of LXRβ/ABCA1 pathway alleviates cochlear hair cell senescence of C57BL/6 J mice via reducing lipid droplet accumulation.Biogerontology · 2025Article
- Pharmacological effects, molecular mechanisms and strategies to improve bioavailability of curcumin in the treatment of neurodegenerative diseases.Frontiers in pharmacology · 2025Review
- The role of NLRP3 inflammasome in multiple sclerosis: pathogenesis and pharmacological application.Frontiers in immunology · 2025Review
- Novel Arf1 Inhibitors Drive Cancer Stem Cell Aging and Potentiate Anti-Tumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation.Nature communications · 2024Article
- Anti-ferroptosis exosomes engineered for targeting M2 microglia to improve neurological function in ischemic stroke.Journal of nanobiotechnology · 2024Article
- Liposome-Mediated Anti-Viral Drug Delivery Across Blood-Brain Barrier: Can Lipid Droplet Target Be Game Changers?Cellular and molecular neurobiology · 2023Review
- A neuron-immune circuit regulates neurodegeneration in the hindbrain and spinal cord of Arf1-ablated mice.National science review · 2023Article
- Blockade of Arf1-mediated lipid metabolism in cancers promotes tumor infiltration of cytotoxic T cells via the LPE-PPARγ-NF-κB-CCL5 pathway.Life metabolism · 2023Article
- Editorial: The relationship of neuroinflammation with aging and neurodegenerative diseases.Frontiers in aging neuroscience · 2022Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Peroxidated lipids accumulate in the presence of reactive oxygen species and are linked to neurodegenerative diseases. Here we find that neuronal ablation of ARF1, a small GTPase important for lipid homeostasis, promoted accumulation of peroxidated lipids, lipid droplets and ATP in the mouse brain and led to neuroinflammation, demyelination and neurodegeneration, mainly in the spinal cord and hindbrain. Ablation of ARF1 in cultured primary neurons led to an increase in peroxidated lipids in co-cultured microglia, activation of the microglial NLRP3 inflammasome and release of inflammatory cytokines in an Apolipoprotein E-dependent manner. Deleting the Nlrp3 gene rescued the neurodegenerative phenotypes in the neuronal Arf1-ablated mice. We also observed a reduction in ARF1 in human brain tissue from patients with amyotrophic lateral sclerosis and multiple sclerosis. Together, our results uncover a previously unrecognized role of peroxidated lipids released from damaged neurons in activation of a neurotoxic microglial NLRP3 pathway that may play a role in human neurodegeneration.
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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.