ArticleProceedings of the National Academy of Sciences of the United States of America2022
De novo designed protein inhibitors of amyloid aggregation and seeding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 77 citations in OpenAlex.
- TAF15 amyloids propagate via defined motifs in a prion-like fashion.Nature communications · 2026Article
- α/Sulfonyl-γ-AApeptide foldamers mitigate Alzheimer's disease pathology by stabilizing transient helical domains in Aβ.Nature communications · 2026Article
- A Highly Sensitive Water-Soluble Donor-Acceptor Dye for Early-Stage Amyloid Aggregation Kinetics.The journal of physical chemistry. B · 2026Article
- Distinct TAF15 amyloid filament folds define multiple subtypes of FTLD-TAF15.bioRxiv : the preprint server for biology · 2026Article
- Peptide-Based Therapeutics for Alzheimer's Disease: Medicinal Chemistry, AI-Guided Computational Design, and Blood-Brain Barrier Delivery.Drug design, development and therapy · 2026Review
- Antimicrobial Peptides as Cross-Seeding Modulators at the Neurodegenerative-Infectious Interface.Research (Washington, D.C.) · 2026Review
- A genetically encoded selection for amyloid-β oligomer binders.Nature chemical biology · 2025Article
- Zinc finger domains bind low-complexity domain polymers.Nature communications · 2025Article
- Artificial intelligence in drug development for delirium and Alzheimer's disease.Acta pharmaceutica Sinica. B · 2025Review
- Antiparallel β-Sheet as a Key Motif of Amyloid-β Inhibitor Designed via Topological Peptide Reprogramming.Angewandte Chemie (International ed. in English) · 2025Article
- Structure-based discovery of forsythoside A as an effective inhibitor to reduce the neurotoxicity of amyloid β.Communications chemistry · 2025Article
- Generating the polymorph landscapes of amyloid fibrils using AI: RibbonFold.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Focus on the Link Between Metal Dyshomeostasis, Norepinephrine, and Protein Aggregation.Antioxidants (Basel, Switzerland) · 2025Review
- Review
- Repurposing Anidulafungin for Alzheimer's Disease via Fragment-Based Drug Discovery.ACS chemical neuroscience · 2024Article
- TDP-43 Promotes Amyloid-Beta Toxicity by Delaying Fibril Maturation via Direct Molecular Interaction.ACS chemical neuroscience · 2024Article
- Design of amyloidogenic peptide traps.Nature chemical biology · 2024Article
- Article
- Review
- Lung endothelium, tau, and amyloids in health and disease.Physiological reviews · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Neurodegenerative diseases are characterized by the pathologic accumulation of aggregated proteins. Known as amyloid, these fibrillar aggregates include proteins such as tau and amyloid-β (Aβ) in Alzheimer's disease (AD) and alpha-synuclein (αSyn) in Parkinson's disease (PD). The development and spread of amyloid fibrils within the brain correlates with disease onset and progression, and inhibiting amyloid formation is a possible route toward therapeutic development. Recent advances have enabled the determination of amyloid fibril structures to atomic-level resolution, improving the possibility of structure-based inhibitor design. In this work, we use these amyloid structures to design inhibitors that bind to the ends of fibrils, "capping" them so as to prevent further growth. Using de novo protein design, we develop a library of miniprotein inhibitors of 35 to 48 residues that target the amyloid structures of tau, Aβ, and αSyn. Biophysical characterization of top in silico designed inhibitors shows they form stable folds, have no sequence similarity to naturally occurring proteins, and specifically prevent the aggregation of their targeted amyloid-prone proteins in vitro. The inhibitors also prevent the seeded aggregation and toxicity of fibrils in cells. In vivo evaluation reveals their ability to reduce aggregation and rescue motor deficits in
Indexed as
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.