ArticleScientific reports2023
Extracellular tau stimulates phagocytosis of living neurons by activated microglia via Toll-like 4 receptor-NLRP3 inflammasome-caspase-1 signalling axis.
Article in Scientific reports, 2023. 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, 26 citations in OpenAlex.
- Protein kinase CK2α' as a dual modulator of neuroimmune signaling and synaptic dysfunction in tauopathy.Translational neurodegeneration · 2026Article
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- Microglial phagocytosis of bipolar cells triggers inner retinal degeneration in Rs1-KO mice.Cell communication and signaling : CCS · 2026Article
- Effects of Exogenous SARS-CoV-2 S1 Protein and mRNA Vaccines on Mixed Neuronal-Glial Cell Cultures.Medicina (Kaunas, Lithuania) · 2026Article
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Tau abnormalities and microglial remodeling in glaucoma: potential links to phagocytosis-related injury.Frontiers in neurology · 2026Review
- Protein kinase CK2α' as a dual modulator of immune signaling and synaptic dysfunction in Tauopathy.bioRxiv : the preprint server for biology · 2025Article
- Tau, amyloid-β and α-synuclein co-pathologies synergistically enhance neuroinflammation and neuropathology.bioRxiv : the preprint server for biology · 2025Article
- Cell autonomous microglia defects in a stem cell model of frontotemporal dementia tau.Molecular psychiatry · 2025Article
- Approaching therapy of Alzheimer's disease via the antidiabetic drug liraglutide-a study with streptozotocin intracerebroventricularly treated Wistar rats.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- ZipAEr: A compressive convolutional autoencoder for high-dimensional spatial omics data at subcellular resolution.Research square · 2025Article
- A Single-Chain Variable Fragment Antibody Alleviates Inflammation and Apoptosis of Neurons by Inhibiting Tau Aggregation.Biomolecules · 2025Article
- 9-Hydroxyaristoquinolone: A New Indole Alkaloid Isolated fromInternational journal of molecular sciences · 2025Article
- Bridging traditional Chinese medicine and Alzheimer's disease: the pivotal role of gut microbiota in multitarget therapeutic mechanisms.Frontiers in pharmacology · 2025Review
- IRF3 regulates neuroinflammatory responses and the expression of genes associated with Alzheimer's disease.Journal of neuroinflammation · 2024Article
- Inflammatory aspects of Alzheimer's disease.Acta neuropathologica · 2024Review
- Cell autonomous microglia defects in a stem cell model of frontotemporal dementia.medRxiv : the preprint server for health sciences · 2024Article
- Pilot Study of the Total and Phosphorylated Tau Proteins in Early-Stage Multiple Sclerosis.Medicina (Kaunas, Lithuania) · 2024Article
- Sesamin ameliorates nonalcoholic steatohepatitis through inhibiting hepatocyte pyroptosisFrontiers in pharmacology · 2024Article
- Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer's Disease.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In tauopathies, abnormal deposition of intracellular tau protein followed by gradual elevation of tau in cerebrospinal fluids and neuronal loss has been documented, however, the mechanism how actually neurons die under tau pathology is largely unknown. We have previously shown that extracellular tau protein (2N4R isoform) can stimulate microglia to phagocytose live neurons, i.e. cause neuronal death by primary phagocytosis, also known as phagoptosis. Here we show that tau protein induced caspase-1 activation in microglial cells via 'Toll-like' 4 (TLR4) receptors and neutral sphingomyelinase. Tau-induced neuronal loss was blocked by caspase-1 inhibitors (Ac-YVAD-CHO and VX-765) as well as by TLR4 antibodies. Inhibition of caspase-1 by Ac-YVAD-CHO prevented tau-induced exposure of phosphatidylserine on the outer leaflet of neuronal membranes and reduced microglial phagocytic activity. We also show that suppression of NLRP3 inflammasome, which is down-stream of TLR4 receptors and mediates caspase-1 activation, by a specific inhibitor (MCC550) also prevented tau-induced neuronal loss. Moreover, NADPH oxidase is also involved in tau-induced neurotoxicity since neuronal loss was abolished by its pharmacological inhibitor. Overall, our data indicate that extracellular tau protein stimulates microglia to phagocytose live neurons via Toll-like 4 receptor-NLRP3 inflammasome-caspase-1 axis and NADPH oxidase, each of which may serve as a potential molecular target for pharmacological treatment of tauopathies.
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