ArticleProceedings of the National Academy of Sciences of the United States of America2017
Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 222 citations in OpenAlex.
- Polyol-Functionalized Manganese-Based Nanoparticles: From Insulin Amyloid Inhibition to Nanozyme-Mediated Antioxidant Activity.International journal of molecular sciences · 2026Article
- Novel hydroxytyrosol esters as potential anti-amyloid and neuroprotective agents for Alzheimer's disease.RSC medicinal chemistry · 2026Article
- Glucagon-Like Peptide-1 Receptor Agonists Inhibit the Initiation of Toxic Amyloid-β42 Aggregation.Journal of the American Chemical Society · 2026Article
- Peptide-based therapeutics in the management of Alzheimer's disease (AD) and their potential to develop novel strategies.Metabolic brain disease · 2026Review
- A molecular perspective of gelsolin amyloidosis: An old foe with new faces.Cellular and molecular life sciences : CMLS · 2026Review
- Identification of potent high-affinity secondary nucleation inhibitors of Aβ42 aggregation from an ultra-large chemical library using deep docking.Molecular systems biology · 2026Article
- Antimicrobial Peptides as Cross-Seeding Modulators at the Neurodegenerative-Infectious Interface.Research (Washington, D.C.) · 2026Review
- Virtual screening of drugs against multiple targets of Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Article
- From Pathology to Materials Science and Engineering: Harnessing the Amyloid State for Biotechnological Applications.ACS applied materials & interfaces · 2025Review
- Aβ42 promotes the aggregation of α-synuclein splice isoforms via heterogeneous nucleation.FEBS letters · 2025Article
- Nanoplasmonic Infrared Microarray Sensor Enabling Structural Protein Biomarker-Based Drug Screening for Neurodegenerative Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Design of Tau Aggregation Inhibitors Using Iterative Machine Learning and a Polymorph-Specific Brain-Seeded Fibril Amplification Assay.Journal of the American Chemical Society · 2025Article
- CASTER-DTA: Equivariant Graph Neural Networks for Predicting Drug-Target Affinity.bioRxiv : the preprint server for biology · 2025Article
- Modulation of Amyloid-β Aggregation by Surface Proteins from Pathogens Associated with Alzheimer's Disease.ACS chemical neuroscience · 2025Article
- CASTER-DTA: equivariant graph neural networks for predicting drug-target affinity.Briefings in bioinformatics · 2025Article
- Charged peptides enriched in aromatic residues decelerate condensate ageing driven by cross-β-sheet formation.Nature communications · 2025Article
- An aminosterol breaks the autocatalytic cycle of AβProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structure-based discovery of forsythoside A as an effective inhibitor to reduce the neurotoxicity of amyloid β.Communications chemistry · 2025Article
- Optimization of a High-Throughput Screen for Monitoring Disease-Associated Protein Misfolding and Aggregation in Bacteria.ACS synthetic biology · 2025Article
- The Role of α-Synuclein-DNAJB6b Coaggregation in Amyloid Suppression.ACS chemical neuroscience · 2025Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer's disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a read-out the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery.
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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.