ArticleCell death & disease2025
The TRPV1-PKM2-SREBP1 axis maintains microglial lipid homeostasis in Alzheimer's disease.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Spatiotemporal heterogeneity and dynamic evolution of microglial glucose metabolic reprogramming in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Molecular target for neuroinflammation and pain management: transient receptor potential vanilloid 1.Inflammopharmacology · 2026Review
- Fatty acid amide hydrolase inhibition for treatment of amyotrophic lateral sclerosis.JCI insight · 2026Article
- Circular RNAEnvironment & health (Washington, D.C.) · 2026Article
- Astrocytic SCAP deletion ameliorates diabetes-associated cognitive impairment by suppressing microglial neuroinflammation and lipid droplet accumulation via the LCN2-24p3R-mTOR axis.Cell death & disease · 2026Article
- Lipid Metabolism Reprogramming in the Aging Brain: Glial-Mediated Pathogenic Mechanisms and Translational Strategies in Neurodegeneration.International journal of molecular sciences · 2026Review
- Reproducibility-driven discovery and systematic benchmarking reveal a robust cerebrospinal fluid proteomic signature in Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Inhibition of Microglial TRPV1 Ameliorates Brain Injury After Intracerebral Hemorrhage by Suppressing AMPK/PINK1-Mediated Mitophagy.CNS neuroscience & therapeutics · 2026Article
- Type 2 Diabetes Mellitus as a Multisystem Disease: From Insulin Resistance to Organ Crosstalk-A Narrative Review.Biomedicines · 2026Review
- Trichostatin A Influences Dendritic Cells' Functions by Regulating Glucose and Lipid Metabolism via PKM2.Molecules (Basel, Switzerland) · 2026Article
- GIPC2 regulation of the PKM2/SREBP1 signaling axis controls adipogenic differentiation of mesenchymal stem cells.Cell death & disease · 2026Article
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
- Capsaicin for cardiometabolic syndrome: multitarget mechanisms and therapeutic potential.Frontiers in nutrition · 2026Review
- Cholinergic regulation of neuroinflammation: linking microglia, immunometabolism, and neuromodulation.Frontiers in immunology · 2026Review
- Transient Receptor Potential Channels as Key Regulators of Neuroinflammation in Neurological Disorders: Mechanistic Insights, Therapeutic Potentials, and Future Directions.CNS neuroscience & therapeutics · 2025Review
- Mechanisms of high-density lipoprotein in regulating blood-brain barrier function: insights and implications.Fluids and barriers of the CNS · 2025Review
- Review
- Emerging Insights into Brain Inflammation: Stem-Cell-Based Approaches for Regenerative Medicine.International journal of molecular sciences · 2025Review
- Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research.Molecular neurodegeneration · 2025Review
- Brain TRPV1 channel-mediated calcium influx: the immunomodulatory pathway of acupuncture in neuroinflammation.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Microglia are progressively activated by inflammation and exhibit phagocytic dysfunction in the pathogenesis of neurodegenerative diseases. Lipid-droplet-accumulating microglia were identified in the aging mouse and human brain; however, little is known about the formation and role of lipid droplets in microglial neuroinflammation of Alzheimer's disease (AD). Here, we report a striking buildup of lipid droplets accumulation in microglia in the 3xTg mouse brain. Moreover, we observed significant upregulation of PKM2 and sterol regulatory element binding protein 1 (SREBP1) levels, which were predominantly localized in microglia of 3xTg mice. PKM2 dimerization was necessary for SREBP1 activation and lipogenesis of lipid droplet-accumulating microglia. RNA sequencing analysis of microglia isolated from 3xTg mice exhibited transcriptomic changes in lipid metabolism, innate inflammation, and phagocytosis dysfunction; these changes were improved with capsaicin-mediated pharmacological activation of TRPV1 via inhibition of PKM2 dimerization and reduction of SREBP1 activation. Lipid droplet-accumulating microglia exhibited increased mitochondrial injury accompanied by impaired mitophagy, which was abrogated upon of TRPV1 activation. Capsaicin also rescued neuronal loss, tau pathology, and memory impairment in 3xTg mice. Our study suggests that TRPV1-PKM2-SREBP1 axis regulation of microglia lipid metabolism could be a therapeutic approach to alleviate the consequences of AD.
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