ArticleNature neuroscience2024
TFEB-vacuolar ATPase signaling regulates lysosomal function and microglial activation in tauopathy.
Article in Nature neuroscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 72 citations in OpenAlex.
- Compartment-Specific Lysosomal Heterogeneity in Microglia Is Regulated by Adaptor Protein Complex-4.bioRxiv : the preprint server for biology · 2026Article
- Review
- Article
- CXCL10 contributes to female-specific pathological progression in tauopathy model mice.Journal of neuroinflammation · 2026Article
- The Glial Autophagy-Lysosomal-Inflammation Axis in Alzheimer's Disease: a Unifying Mechanistic Framework.Molecular neurobiology · 2026Review
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Astrocytic lactate shuttle disruption and the energy-starved lysosome in Alzheimer's disease.Research square · 2026Article
- Dysregulation of the TFEB-ATP6V0C axis in microglia exacerbates α-synuclein pathology through impaired lysosomal acidification in Parkinson's disease.Cell death and differentiation · 2026Article
- Ginsenoside Rg1 alleviates post-ischemic stroke neuroinflammation by inhibiting CKLF1-mediated suppression of dead/dying neuron clearance.Acta pharmaceutica Sinica. B · 2026Article
- Blood serum from individuals with Alzheimer's disease alters microglial phagocytosis in vitro.Neural regeneration research · 2026Article
- Gpnmb defines a phagocytic state of microglia linked to cell death in prion disease mouse model.Nature communications · 2026Article
- Mitochondrial iron overload is associated with lysosomal dysfunction-mediated mitophagy impairment in the heart of Friedreich's ataxia.Mitochondrion · 2026Article
- NDST3 suppression restores lysosomal acidification and ameliorates amyloid-β and MAPT/tau pathology in Alzheimer's disease.Translational neurodegeneration · 2026Article
- Lysosomal cholesteryl ester hydrolysis drives white matter repair by reprogramming microglia into a novel reparative state.Journal of neuroinflammation · 2026Article
- Article
- Spatiotemporal transcriptomic profiling reveals upregulation of glycolysis pathway genes before overt tauopathy in the PS19 mouse model.Experimental & molecular medicine · 2026Article
- Isogenic cortical organoids enable precision targeting of APP variant-specific pathways in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- "Micro-managing" immune activation and protein turnover: microglial lysosomes in the context of health and disease.NPJ dementia · 2026Review
- Lysosomal dysfunction in diabetes and diabetic complications.Frontiers in endocrinology · 2026Review
- Lysosomes as chemical and metabolic organizers of central nervous system injury and repair.Frontiers in chemistry · 2026Review
Corrections and comments
- Update of
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Transcription factor EB (TFEB) mediates gene expression through binding to the coordinated lysosome expression and regulation (CLEAR) sequence. TFEB targets include subunits of the vacuolar ATPase (v-ATPase), which are essential for lysosome acidification. Single-nucleus RNA sequencing of wild-type and PS19 (Tau) transgenic mice expressing the P301S mutant tau identified three unique microglia subclusters in Tau mice that were associated with heightened lysosome and immune pathway genes. To explore the lysosome-immune relationship, we specifically disrupted the TFEB-v-ATPase signaling by creating a knock-in mouse line in which the CLEAR sequence of one of the v-ATPase subunits, Atp6v1h, was mutated. CLEAR mutant exhibited a muted response to TFEB, resulting in impaired lysosomal acidification and activity. Crossing the CLEAR mutant with Tau mice led to higher tau pathology but diminished microglia response. These microglia were enriched in a subcluster low in mTOR and HIF-1 pathways and were locked in a homeostatic state. Our studies demonstrate a physiological function of TFEB-v-ATPase signaling in maintaining lysosomal homeostasis and a critical role of the lysosome in mounting a microglia and immune response in tauopathy and Alzheimer's disease.
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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.