ArticleNature communications2022
Structure-based discovery of small molecules that disaggregate Alzheimer's disease tissue derived tau fibrils in vitro.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 178 citations in OpenAlex.
- Synthesis and multi-target evaluation of 2-(2-phenylethyl)/2,3-styrylchromone derivatives as potential anti-Alzheimer's disease agents.Molecular diversity · 2026Article
- Tau Disaggregation by a CNS-Permeable Small Molecule Reduces Fibril and Oligomer Burden and Preserves Proteostasis and Behavior.bioRxiv : the preprint server for biology · 2026Article
- The Enigma of Big Tau Exon 4a: Genomic Architecture, Biophysical Identity, and Unique Evolutionary Mechanisms.Biomolecules · 2026Review
- Elimination of tau tangles and soluble aggregates with the small molecule ACI-16664 prevents neurodegeneration in vivo.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Spirooxindoles as Disruptors of Preformed Hen Egg White Lysozyme Fibrils as a Model for Neurodegenerative Diseases.ChemMedChem · 2026Article
- Machine learning-assisted screening of small-molecule drugs for suppressing protein aggregation and ROS generation based on ECL and CV dual-mode signals amplified by DNA.Chemical science · 2026Article
- Cinnamon Bud Extract Is a Source of Biomolecules Active against the Aggregation and Condensation of Alzheimer's-Associated Tau Protein.Journal of agricultural and food chemistry · 2026Article
- Blood-brain barrier-penetrative lipid nanoparticles enable systemic delivery of TRIM11 mRNA to disaggregate Tau in Alzheimer's disease models.Cell reports. Medicine · 2026Article
- Polyphyletic screen defines distinct classes of plant-derived natural products that oppose tauopathy.Life science alliance · 2026Article
- Glycosidic scaffold bearing multiple galloyl moieties from pomegranate disrupts transthyretin amyloids.iScience · 2026Article
- Heterogeneous Dynamics of the Fuzzy Coat of Full-Length Phospho-Mimetic Tau Fibrils.Journal of the American Chemical Society · 2026Article
- Distinct TAF15 amyloid filament folds define multiple subtypes of FTLD-TAF15.bioRxiv : the preprint server for biology · 2026Article
- The Many Lives of a Single Sequence: Functional Plasticity Through Amyloid Polymorphism.Sub-cellular biochemistry · 2026Review
- Tau protein in Parkinson's disease: advances in phosphoproteomics and molecular dynamics simulations.Frontiers in aging neuroscience · 2026Review
- Epigallocatechin-3-Gallate: A potential amyloid Fibril Disaggregator of Serum amyloid A1.Biochemistry and biophysics reports · 2025Article
- FibrilPaint to determine the length of Tau amyloids in fluids.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- High-throughput discovery of fluoroprobes that recognize amyloid fibril polymorphs.Nature chemistry · 2025Article
- Design and application of a Tau seed amplification assay for screening inhibitors of Tau seeding.Alzheimer's research & therapy · 2025Article
- Polyphenol-Mediated Peptide Assembly Modulates Melittin Toxicity: A Structure-Activity Strategy for Neutralizing the Interface Affinity of Pore-Forming Toxins to Cell Membranes.ACS applied materials & interfaces · 2025Article
- Significant downregulation of Alzheimer's amyloid-β levels enabled by engineered DNA nanomaterials.Fundamental research · 2025Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is the consequence of neuronal death and brain atrophy associated with the aggregation of protein tau into fibrils. Thus disaggregation of tau fibrils could be a therapeutic approach to AD. The small molecule EGCG, abundant in green tea, has long been known to disaggregate tau and other amyloid fibrils, but EGCG has poor drug-like properties, failing to fully penetrate the brain. Here we have cryogenically trapped an intermediate of brain-extracted tau fibrils on the kinetic pathway to EGCG-induced disaggregation and have determined its cryoEM structure. The structure reveals that EGCG molecules stack in polar clefts between the paired helical protofilaments that pathologically define AD. Treating the EGCG binding position as a pharmacophore, we computationally screened thousands of drug-like compounds for compatibility for the pharmacophore, discovering several that experimentally disaggregate brain-derived tau fibrils in vitro. This work suggests the potential of structure-based, small-molecule drug discovery for amyloid diseases.
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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.