ArticleProceedings of the National Academy of Sciences of the United States of America2014
Clioquinol promotes the degradation of metal-dependent amyloid-β (Aβ) oligomers to restore endocytosis and ameliorate Aβ toxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 165 citations in OpenAlex.
- Clioquinol inactivates thiamine pyrophosphate by increasing cellular oxidative stress.Redox biology · 2026Article
- Behavioral, Histopathological, and Biochemical Implications of Aloe Emodin in Copper-Aβ-Induced Alzheimer's Disease-like Model Rats.Current issues in molecular biology · 2026Article
- From Yeast to Therapeutics: Modeling Neurodegenerative Diseases in Saccharomyces cerevisiae.Yeast (Chichester, England) · 2025Review
- Copper homeostasis and cuproptosis in Alzheimer's disease (Review).International journal of molecular medicine · 2025Review
- Targeting the awry Aβ pathway in Alzheimer's disease: hype and hurdles.Inflammopharmacology · 2025Review
- β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.Cell chemical biology · 2025Article
- Sodium Thiosulfate: An Innovative Multi-Target Repurposed Treatment Strategy for Late-Onset Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Trajectory of brain-derived amyloid beta in Alzheimer's disease: where is it coming from and where is it going?Translational neurodegeneration · 2024Review
- Article
- Screening Techniques for Drug Discovery in Alzheimer's Disease.ACS omega · 2024Review
- Simple model systems reveal conserved mechanisms of Alzheimer's disease and related tauopathies.Molecular neurodegeneration · 2023Review
- Broad susceptibility ofmBio · 2023Article
- Alzheimer's Disease: Significant Benefit from the Yeast-Based Models.International journal of molecular sciences · 2023Review
- Review
- Copper chelating cyclic peptidomimetic inhibits Aβ fibrillogenesis.RSC medicinal chemistry · 2022Article
- Modeling Alzheimer's Disease inBiomedicines · 2022Review
- UsingFrontiers in pharmacology · 2022Review
- Amelioration of Alzheimer's disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow.Nature biomedical engineering · 2022Article
- Advances in PPARs Molecular Dynamics and Glitazones as a Repurposing Therapeutic Strategy through Mitochondrial Redox Dynamics against Neurodegeneration.Current neuropharmacology · 2022Review
- Exposure of metal toxicity in Alzheimer's disease: An extensive review.Frontiers in pharmacology · 2022Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a common, progressive neurodegenerative disorder without effective disease-modifying therapies. The accumulation of amyloid-β peptide (Aβ) is associated with AD. However, identifying new compounds that antagonize the underlying cellular pathologies caused by Aβ has been hindered by a lack of cellular models amenable to high-throughput chemical screening. To address this gap, we use a robust and scalable yeast model of Aβ toxicity where the Aβ peptide transits through the secretory and endocytic compartments as it does in neurons. The pathogenic Aβ 1-42 peptide forms more oligomers and is more toxic than Aβ 1-40 and genome-wide genetic screens identified genes that are known risk factors for AD. Here, we report an unbiased screen of ∼140,000 compounds for rescue of Aβ toxicity. Of ∼30 hits, several were 8-hydroxyquinolines (8-OHQs). Clioquinol (CQ), an 8-OHQ previously reported to reduce Aβ burden, restore metal homeostasis, and improve cognition in mouse AD models, was also effective and rescued the toxicity of Aβ secreted from glutamatergic neurons in Caenorhabditis elegans. In yeast, CQ dramatically reduced Aβ peptide levels in a copper-dependent manner by increasing degradation, ultimately restoring endocytic function. This mirrored its effects on copper-dependent oligomer formation in vitro, which was also reversed by CQ. This unbiased screen indicates that copper-dependent Aβ oligomer formation contributes to Aβ toxicity within the secretory/endosomal pathways where it can be targeted with selective metal binding compounds. Establishing the ability of the Aβ yeast model to identify disease-relevant compounds supports its further exploitation as a validated early discovery platform.
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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.