ArticleJournal of biomolecular screening2014
AlphaScreen HTS and live-cell bioluminescence resonance energy transfer (BRET) assays for identification of Tau-Fyn SH3 interaction inhibitors for Alzheimer disease.
Article in Journal of biomolecular screening, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Multiple and Alternative Sites Make Tau Protein an Adaptable Sticky Surface for the SH3 Domain of Fyn Kinase.Angewandte Chemie (International ed. in English) · 2025Article
- Screening Techniques for Drug Discovery in Alzheimer's Disease.ACS omega · 2024Review
- Development of small-molecule Tau-SH3 interaction inhibitors that prevent amyloid-β toxicity and network hyperexcitability.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Enhanced Fyn-tau and NR2B-PSD95 interactions in epileptic foci in experimental models and human epilepsy.Brain communications · 2024Article
- Fyn nanoclustering requires switching to an open conformation and is enhanced by FTLD-Tau biomolecular condensates.Molecular psychiatry · 2023Article
- Optimization of BRET saturation assays for robust and sensitive cytosolic protein-protein interaction studies.Scientific reports · 2022Article
- Alzheimer's disease risk geneeLife · 2020Article
- A peptide inhibitor of Tau-SH3 interactions ameliorates amyloid-β toxicity.Neurobiology of disease · 2020Article
- Rodent models for Alzheimer disease.Nature reviews. Neuroscience · 2018Review
- Phosphorylation of tau at Y18, but not tau-fyn binding, is required for tau to modulate NMDA receptor-dependent excitotoxicity in primary neuronal culture.Molecular neurodegeneration · 2017Article
- Critical residues involved in tau binding to fyn: implications for tau phosphorylation in Alzheimer's disease.Acta neuropathologica communications · 2016Article
- Directed Evolution of a Highly Specific FN3 Monobody to the SH3 Domain of Human Lyn Tyrosine Kinase.PloS one · 2016Article
- Fluorescence anisotropy (polarization): from drug screening to precision medicine.Expert opinion on drug discovery · 2015Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer disease (AD) is the most common neurodegenerative disease, and with Americans' increasing longevity, it is becoming an epidemic. There are currently no effective treatments for this disorder. Abnormalities of Tau track more closely with cognitive decline than the most studied therapeutic target in AD, amyloid-β, but the optimal strategy for targeting Tau has not yet been identified. On the basis of considerable preclinical data from AD models, we hypothesize that interactions between Tau and the Src-family tyrosine kinase, Fyn, are pathogenic in AD. Genetically reducing either Tau or Fyn is protective in AD mouse models, and a dominant negative fragment of Tau that alters Fyn localization is also protective. Here, we describe a new AlphaScreen assay and a live-cell bioluminescence resonance energy transfer (BRET) assay using a novel BRET pair for quantifying the Tau-Fyn interaction. We used these assays to map the binding site on Tau for Fyn to the fifth and sixth PXXP motifs to show that AD-associated phosphorylation at microtubule affinity regulating kinase sites increases the affinity of the Tau-Fyn interaction and to identify Tau-Fyn interaction inhibitors by high-throughput screening. This screen has identified a variety of chemically tractable hits, suggesting that the Tau-Fyn interaction may represent a good drug target for AD.
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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.