ArticleThe Journal of biological chemistry2015
Identification of a Compound That Disrupts Binding of Amyloid-β to the Prion Protein Using a Novel Fluorescence-based Assay.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 38 citations in OpenAlex.
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Article
- Chicago sky blue 6B inhibits α-synuclein aggregation and propagation.Molecular brain · 2022Article
- Article
- Repurposing approved drugs on the pathway to novel therapies.Medicinal research reviews · 2020Review
- The small molecule Chicago Sky Blue promotes heart repair following myocardial infarction in mice.JCI insight · 2019Article
- Direct interaction of DNMT inhibitors to PrPActa pharmaceutica Sinica. B · 2019Article
- Proteolytic shedding of the prion protein via activation of metallopeptidase ADAM10 reduces cellular binding and toxicity of amyloid-β oligomers.The Journal of biological chemistry · 2019Article
- Discovery of antimicrobial compounds targeting bacterial type FAD synthetases.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- A d-enantiomeric peptide interferes with heteroassociation of amyloid-β oligomers and prion protein.The Journal of biological chemistry · 2018Article
- Organizing biochemistry in space and time using prion-like self-assembly.Current opinion in systems biology · 2018Article
- Pharmacological Agents Targeting the Cellular Prion Protein.Pathogens (Basel, Switzerland) · 2018Review
- Involvement of Cellular Prion Protein in α-Synuclein Transport in Neurons.Molecular neurobiology · 2018Article
- Recombinant PrP and Its Contribution to Research on Transmissible Spongiform Encephalopathies.Pathogens (Basel, Switzerland) · 2017Review
- Soluble Aβ aggregates can inhibit prion propagation.Open biology · 2017Article
- Article
- Identification of approved drugs that inhibit the binding of amyloid β oligomers to ephrin type-B receptor 2.FEBS open bio · 2016Article
- Amyloid-β Receptors: The Good, the Bad, and the Prion Protein.The Journal of biological chemistry · 2016Review
- Functions of the cellular prion protein, the end of Moore's law, and Ockham's razor theory.Prion · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The prion protein (PrP) has been implicated both in prion diseases such as Creutzfeldt-Jakob disease, where its monomeric cellular isoform (PrP(C)) is recruited into pathogenic self-propagating polymers of misfolded protein, and in Alzheimer disease, where PrP(C) may act as a receptor for synaptotoxic oligomeric forms of amyloid-β (Aβ). There has been considerable interest in identification of compounds that bind to PrP(C), stabilizing its native fold and thereby acting as pharmacological chaperones to block prion propagation and pathogenesis. However, compounds binding PrP(C) could also inhibit the binding of toxic Aβ species and may have a role in treating Alzheimer disease, a highly prevalent dementia for which there are currently no disease-modifying treatments. However, the absence of a unitary, readily measurable, physiological function of PrP makes screening for ligands challenging, and the highly heterogeneous nature of Aβ oligomer preparations makes conventional competition binding assays difficult to interpret. We have therefore developed a high-throughput screen that utilizes site-specifically fluorescently labeled protein to identify compounds that bind to PrP and inhibit both Aβ binding and prion propagation. Following a screen of 1,200 approved drugs, we identified Chicago Sky Blue 6B as the first small molecule PrP ligand capable of inhibiting Aβ binding, demonstrating the feasibility of development of drugs to block this interaction. The interaction of Chicago Sky Blue 6B was characterized by isothermal titration calorimetry, and its ability to inhibit Aβ binding and reduce prion levels was established in cell-based assays.
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.