ArticleJournal of neuroinflammation2024
Glutamine metabolism modulates microglial NLRP3 inflammasome activity through mitophagy in Alzheimer's disease.
Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Targeting mannosylation of nicastrin N-glycans attenuates γ-secretase activity and notch-dependent leukemia progression.The Journal of clinical investigation · 2026Article
- Dihydromyricetin ameliorates cognitive dysfunction in SAMP8 mice via autophagy-mediated degradation of the NLRP3 inflammasome.Metabolic brain disease · 2026Article
- Pyrroloquinoline Quinone Attenuates Traumatic Brain Injury-Induced Secondary Damage by Activating PINK1/Parkin-Mediated Mitophagy and Suppressing ASS1/CPS1-Driven Arginine Biosynthesis.CNS neuroscience & therapeutics · 2026Article
- Metabolic Reprogramming of Brain Microglia: Implications for Aging and Aging-Associated Neurodegenerative Diseases.Aging cell · 2026Review
- Microglial mitophagy as an immunometabolic checkpoint in alzheimer's disease: linking mitochondrial quality control to neuroinflammation.Journal of neuroinflammation · 2026Review
- Reprogramming Neuroinflammation: Mitochondrial Targets and Immune Checkpoint Inhibitors in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Serum amino acid levels are associated with brain hypometabolism in patients across the Alzheimer's disease continuum.IBRO neuroscience reports · 2026Article
- LLPS Inflammasome Metabo-Proteostatic Failure Axis in AD: Mechanistic and Translational Insights.Molecular neurobiology · 2026Review
- Intranasal Adipose-Derived MSC Extracellular Vesicles Confer Sustained Cognitive Improvement and Suppress Alzheimer's Pathology in APP/PS1 Mice.Biomolecules · 2026Article
- Metabolic Reprogramming of Microglia in Neuroinflammation and Depression.International journal of molecular sciences · 2026Review
- ANGPTL2 inhibits macrophage pyroptosis and alleviates rheumatoid arthritis progression by regulating mitophagy via IGFBP5.Cell death & disease · 2026Article
- Regulation of autophagy-mediated pathways by diet, physical activity, and sleep in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Investigating the molecular mechanisms of glutamine metabolism and mitochondria-related biomarkers in Alzheimer's disease through transcriptomics and experimental validation.European journal of medical research · 2026Article
- Influence of blood-brain barrier and intestinal barrier on microglial phenotypes: a perspective of clinical and prognostic implications.Frontiers in immunology · 2026Article
- From metabolism to neurodegeneration: how microglial functional reprogramming drives neurodegenerative diseases.Frontiers in molecular neuroscience · 2026Review
- Using Blood-Based Biomarkers to Facilitate the Diagnosis of Alzheimer's Disease: Insights from a Novel Pyroptosis-Associated Molecular Signature Model.Molecular neurobiology · 2025Article
- Metabolic Flexibility of Microglia: Energy Substrate Utilization and Impact on Neuronal Metabolism.Journal of neurochemistry · 2025Article
- Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype.Journal of neuroinflammation · 2025Article
- Neuroprotective mechanisms of microglia in ischemic stroke: a review focused on mitochondria.Molecular biology reports · 2025Review
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Authors and funding
7 authors.
Funding
Abstract
The NLR family pyrin domain containing 3 (NLRP3) inflammasome in microglia is intimately linked to the pathogenesis of Alzheimer's disease (AD). Although NLRP3 inflammasome activity is regulated by cellular metabolism, the underlying mechanism remains elusive. Here, we found that under the pathological conditions of AD, the activation of NLRP3 inflammasome in microglia is accompanied by increased glutamine metabolism. Suppression of glutaminase, the rate limiting enzyme in glutamine metabolism, attenuated the NLRP3 inflammasome activation both in the microglia of AD mice and cultured inflammatory microglia. Mechanistically, inhibiting glutaminase blocked the anaplerotic flux of glutamine to the tricarboxylic acid cycle and amino acid synthesis, down-regulated mTORC1 signaling by phosphorylating AMPK, which stimulated mitophagy and limited the accumulation of intracellular reactive oxygen species, ultimately prevented the activation of NLRP3 inflammasomes in activated microglia during AD. Taken together, our findings suggest that glutamine metabolism regulates the activation of NLRP3 inflammasome through mitophagy in microglia, thus providing a potential therapeutic target for AD treatment.
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