ArticleScience advances2016
An anticancer drug suppresses the primary nucleation reaction that initiates the production of the toxic Aβ42 aggregates linked with Alzheimer's disease.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.
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
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.
- Anticancer drugs repurposed for Alzheimer's disease: a systematic review.Alzheimer's research & therapy · 2021Pooled it
- Synthesis of Phenyl 2-Acetamidoselenogalactoside Mimetics and Interaction with Amyloid βPharmaceuticals (Basel, Switzerland) · 2026Article
- Metabolomic Relationships Between Lung Cancer and Alzheimer's Disease Using Serum Nuclear Magnetic Resonance Spectroscopy.NMR in biomedicine · 2026Article
- Disease-disease interactions: molecular links of neurodegenerative diseases with cancer, viral infections, and type 2 diabetes.Translational neurodegeneration · 2025Review
- Charged peptides enriched in aromatic residues decelerate condensate ageing driven by cross-β-sheet formation.Nature communications · 2025Article
- Protein aggregation and neurodegenerative disease: Structural outlook for the novel therapeutics.Proteins · 2025Review
- Structure-based discovery of forsythoside A as an effective inhibitor to reduce the neurotoxicity of amyloid β.Communications chemistry · 2025Article
- Anti-Inflammatory Peptide Prevents AβCells · 2025Article
- A high precision method of segmenting complex postures in Caenorhabditis elegans and deep phenotyping to analyze lifespan.Scientific reports · 2025Article
- Repurposing Anidulafungin for Alzheimer's Disease via Fragment-Based Drug Discovery.ACS chemical neuroscience · 2024Article
- CoVAMPnet: Comparative Markov State Analysis for Studying Effects of Drug Candidates on Disordered Biomolecules.JACS Au · 2024Article
- Kinetic models reveal the interplay of protein production and aggregation.Chemical science · 2024Article
- Protein mimetic 2D FAST rescues alpha synuclein aggregation mediated early and post disease Parkinson's phenotypes.Nature communications · 2024Article
- A Relationship between the Structures and Neurotoxic Effects of Aβ Oligomers Stabilized by Different Metal Ions.ACS chemical neuroscience · 2024Article
- The thermodynamics of neurodegenerative disease.Biophysics reviews · 2024Review
- Maturation-dependent changes in the size, structure and seeding capacity of Aβ42 amyloid fibrils.Communications biology · 2024Article
- A Biomimetic Multiparametric Assay to Characterise Anti-Amyloid Drugs.International journal of molecular sciences · 2023Article
- A Nanoparticle-Based Model System for the Study of Heterogeneous Nucleation Phenomena.Langmuir : the ACS journal of surfaces and colloids · 2023Article
- Combinations of Vitamin A and Vitamin E Metabolites Confer Resilience against Amyloid-β Aggregation.ACS chemical neuroscience · 2023Article
- Enhanced surface nanoanalytics of transient biomolecular processes.Science advances · 2023Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The conversion of the β-amyloid (Aβ) peptide into pathogenic aggregates is linked to the onset and progression of Alzheimer's disease. Although this observation has prompted an extensive search for therapeutic agents to modulate the concentration of Aβ or inhibit its aggregation, all clinical trials with these objectives have so far failed, at least in part because of a lack of understanding of the molecular mechanisms underlying the process of aggregation and its inhibition. To address this problem, we describe a chemical kinetics approach for rational drug discovery, in which the effects of small molecules on the rates of specific microscopic steps in the self-assembly of Aβ42, the most aggregation-prone variant of Aβ, are analyzed quantitatively. By applying this approach, we report that bexarotene, an anticancer drug approved by the U.S. Food and Drug Administration, selectively targets the primary nucleation step in Aβ42 aggregation, delays the formation of toxic species in neuroblastoma cells, and completely suppresses Aβ42 deposition and its consequences in a Caenorhabditis elegans model of Aβ42-mediated toxicity. These results suggest that the prevention of the primary nucleation of Aβ42 by compounds such as bexarotene could potentially reduce the risk of onset of Alzheimer's disease and, more generally, that our strategy provides a general framework for the rational identification of a range of candidate drugs directed against neurodegenerative disorders.
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.