ArticleScience advances2021
Microglia become hypofunctional and release metalloproteases and tau seeds when phagocytosing live neurons with P301S tau aggregates.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
What it found
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Who cites it
95 citing papers in PubMed.
- Youth-associated protein TIMP2 regulates microglial state and function in healthy and aged mice.Nature communications · 2026Article
- Distinct factors drive the progression of tau pathology in Alzheimer's disease.Fundamental research · 2026Review
- Atypical involvement of Alzheimer's tau proteins in diseases beyond tauopathies.Life medicine · 2026Review
- Type-1 interferons associated with microglial-mediated neuroinflammation in Alzheimer's disease.Journal of neuroinflammation · 2026Review
- Timing of microglial ablation determines protection from tau-mediated neurodegeneration and cognitive decline.Acta neuropathologica communications · 2026Article
- Alzheimer's disease: from molecular pathways to therapies.Molecular biomedicine · 2026Review
- Unraveling the molecular mechanisms of aluminium chloride-induced Alzheimer's disease.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- The Mitochondrial Guardian α-Amyrin Mitigates Alzheimer's Disease Pathology via Modulation of the DLK-SARM1-ULK1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Phosphorylated tau exhibits antimicrobial activity capable of neutralizing herpes simplex virus 1 infectivity in human neurons.Nature neuroscience · 2026Article
- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- Basic Microglial Functions and How They Go Awry in Neurodegenerative Disease.Annual review of pathology · 2026Review
- Silmitasertib, an FDA-designated orphan CK2 inhibitor, ameliorates neuropathology and motor dysfunction in a Huntington's disease mouse model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Alterations in the brain lipidome of Alzheimer's disease donors with rareBrain communications · 2026Article
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Metal ion dyshomeostasis in neurological disorders: from pathological mechanisms to targeted neuroprotective and regenerative strategies.Frontiers in pharmacology · 2026Review
- Systematic profiling reveals distinct senescence signatures and regulators across human brain cell types.Nature communications · 2025Article
- Extracellular tau clearance is governed by its aggregation state and independent of microglial activation by LPS and IFN-γ.Neurobiology of disease · 2025Article
- Amyloid beta and tau are associated with the dual effect of neuroinflammation on neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Cell autonomous microglia defects in a stem cell model of frontotemporal dementia tau.Molecular psychiatry · 2025Article
- Emerging roles for innate and adaptive immunity in tauopathies.Cell reports · 2025Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The microtubule-associated protein tau aggregates in multiple neurodegenerative diseases, causing inflammation and changing the inflammatory signature of microglia by unknown mechanisms. We have shown that microglia phagocytose live neurons containing tau aggregates cultured from P301S tau mice due to neuronal tau aggregate-induced exposure of the “eat me” signal phosphatidylserine. Here, we show that after phagocytosing tau aggregate-bearing neurons, microglia become hypophagocytic while releasing seed-competent insoluble tau aggregates. These microglia express a senescence-like phenotype, demonstrated by acidic β-galactosidase activity, secretion of paracrine senescence-associated cytokines, and maturation of matrix remodeling enzymes, results that are corroborated in P301S mouse brains and ex vivo brain slices. In particular, the nuclear factor κB–dependent activation of matrix metalloprotease 3 (MMP3/stromelysin1) was replicated in brains from patients with tauopathy. These data show that microglia that have been activated to ingest live tau aggregates-bearing neurons behave hormetically, becoming hypofunctional while acting as vectors of tau aggregate spreading.
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.