ArticleThe Journal of biological chemistry2020
Compound screening in cell-based models of tau inclusion formation: Comparison of primary neuron and HEK293 cell assays.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Tau-targeting active immunotherapy slows progression and reduces pathology in mouse models of tauopathy.Brain pathology (Zurich, Switzerland) · 2026Article
- Polyphyletic screen defines distinct classes of plant-derived natural products that oppose tauopathy.Life science alliance · 2026Article
- HDAC6 Inhibition Reduces Seeded Tau and α-Synuclein Pathologies in Primary Neuron Cultures and Wild-Type Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Deubiquitinating Enzymes Ubiquitin-Specific Proteases 7 and 10 Regulate TAU Aggregation.International journal of molecular sciences · 2025Article
- Novel strategies for targeting tau oligomers in neurodegenerative diseases.Journal of neurology · 2025Review
- Targeting Endogenous Tau in Seeded Tauopathy Models Inhibits Tau Spread.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Screening Techniques for Drug Discovery in Alzheimer's Disease.ACS omega · 2024Review
- Selection of lansoprazole from an FDA-approved drug library to inhibit the Alzheimer's disease seed-dependent formation of tau aggregates.Frontiers in aging neuroscience · 2024Article
- Article
- Towards a Mechanistic Model of Tau-Mediated Pathology in Tauopathies: What Can We Learn from Cell-Based In Vitro Assays?International journal of molecular sciences · 2022Review
- A Combined Cell-Worm Approach to Search for Compounds Counteracting the Toxicity of Tau Oligomers In Vivo.International journal of molecular sciences · 2022Article
- A human tau seeded neuronal cell model recapitulates molecular responses associated with Alzheimer's disease.Scientific reports · 2022Article
- UsingFrontiers in pharmacology · 2022Review
- Modeling the mature CNS: A predictive screening platform for neurodegenerative disease drug discovery.Journal of neuroscience methods · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hallmark pathological features of Alzheimer's disease (AD) brains are senile plaques, comprising β-amyloid (Aβ) peptides, and neuronal inclusions formed from tau protein. These plaques form 10-20 years before AD symptom onset, whereas robust tau pathology is more closely associated with symptoms and correlates with cognitive status. This temporal sequence of AD pathology development, coupled with repeated clinical failures of Aβ-directed drugs, suggests that molecules that reduce tau inclusions have therapeutic potential. Few tau-directed drugs are presently in clinical testing, in part because of the difficulty in identifying molecules that reduce tau inclusions. We describe here two cell-based assays of tau inclusion formation that we employed to screen for compounds that inhibit tau pathology: a HEK293 cell-based tau overexpression assay, and a primary rat cortical neuron assay with physiological tau expression. Screening a collection of ∼3500 pharmaceutical compounds with the HEK293 cell tau aggregation assay, we obtained only a low number of hit compounds. Moreover, these compounds generally failed to inhibit tau inclusion formation in the cortical neuron assay. We then screened the Prestwick library of mostly approved drugs in the cortical neuron assay, leading to the identification of a greater number of tau inclusion inhibitors. These included four dopamine D2 receptor antagonists, with D2 receptors having previously been suggested to regulate tau inclusions in a
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