ArticleNature metabolism2023
Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 218 papers, 1 of them a synthesis that pooled it.
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Who cites it
218 citing papers in PubMed, 1 synthesis or guideline pooled it, 269 citations in OpenAlex.
- Therapeutic and biomarker potential of erythropoietin in neurodegenerative diseases: a systematic review.BMC neurology · 2026Pooled 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
- Accelerated hippocampal atrophy in APOE ε4 homozygotes and females: Longitudinal findings from the Tohoku Medical Megabank MRI study.Neuroradiology · 2026Article
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.Neural regeneration research · 2026Article
- Targeting innovative therapeutic approaches to the hallmarks of aging to combat Alzheimer's disease.Neural regeneration research · 2026Article
- Intercellular Mitochondrial Transfer in the Nervous System: Roles of Tunneling Nanotubes, Mitochondrial Extracellular Vesicles, and Neuroimmune Bioenergetic Interactions.Molecular neurobiology · 2026Review
- Neuronal and Astrocytic Lipid Metabolic Coupling Mediates Ozone-Induced Learning and Memory Impairment.Environment & health (Washington, D.C.) · 2026Article
- Age-dependent changes in lipid droplet distribution and vascularization in naked mole rat vs. mouse hippocampus.GeroScience · 2026Article
- ACSL4-mediated astrocyte ferroptosis augments neuroinflammation and exacerbates NMOSD pathology.Cell death and differentiation · 2026Article
- Eugenol regulates ferroptosis through Mfn2/SLC7A11/GPX4 pathway to alleviate glutamate excitotoxicity damage in glaucoma.Molecular and cellular biochemistry · 2026Article
- Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration.The Journal of clinical investigation · 2026Review
- Written in the Stars: Astrocyte Biology From Evolution to Disease.Acta physiologica (Oxford, England) · 2026Review
- Transcriptome and Experimental Verification Identified Candidate Biomarkers Related to Mitochondrial Metabolism in Sepsis-Associated Encephalopathy.Shock (Augusta, Ga.) · 2026Article
- Astragaloside IV mitigates mitochondrial damage and neurological symptoms in rats with cervical spondylotic myelopathy by inhibiting IL-17/TRAF6/NF-κB pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Cerebral Intramural Cells: A Missing Cellular Link Between Vascular Aging and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Review
- Dysfunctional Mitochondria in Microglia Drive Cognitive Aging and Neurodegeneration via cGAS-STING.Neuroscience bulletin · 2026Article
- The roles of microglia and astrocytes in inflammasomes and neurological disorders.Neural regeneration research · 2026Article
- Metabolic crosstalk in the ageing brain: astrocyte-neuron coupling as a target for homeostatic restoration and therapy.Translational neurodegeneration · 2026Review
158 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Astrocytes provide key neuronal support, and their phenotypic transformation is implicated in neurodegenerative diseases. Metabolically, astrocytes possess low mitochondrial oxidative phosphorylation (OxPhos) activity, but its pathophysiological role in neurodegeneration remains unclear. Here, we show that the brain critically depends on astrocytic OxPhos to degrade fatty acids (FAs) and maintain lipid homeostasis. Aberrant astrocytic OxPhos induces lipid droplet (LD) accumulation followed by neurodegeneration that recapitulates key features of Alzheimer's disease (AD), including synaptic loss, neuroinflammation, demyelination and cognitive impairment. Mechanistically, when FA load overwhelms astrocytic OxPhos capacity, elevated acetyl-CoA levels induce astrocyte reactivity by enhancing STAT3 acetylation and activation. Intercellularly, lipid-laden reactive astrocytes stimulate neuronal FA oxidation and oxidative stress, activate microglia through IL-3 signalling, and inhibit the biosynthesis of FAs and phospholipids required for myelin replenishment. Along with LD accumulation and impaired FA degradation manifested in an AD mouse model, we reveal a lipid-centric, AD-resembling mechanism by which astrocytic mitochondrial dysfunction progressively induces neuroinflammation and neurodegeneration.
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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.