ArticleCell reports2014
Zinc binding directly regulates tau toxicity independent of tau hyperphosphorylation.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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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
51 citing papers in PubMed, 110 citations in OpenAlex.
- Zinc Differentially Modulates Tau Aggregation, Fibril Morphology, and Prion-like Seeding in a Construct-Dependent Manner.bioRxiv : the preprint server for biology · 2026Article
- Structural insights into copper and zinc binding to tau protein and the impact of metal binding on amyloid aggregation.Chemical science · 2026Article
- Cell-specific copper dyshomeostasis mechanism in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Extremely Low-Frequency and Low-Intensity Electromagnetic Field Technology (ELF-EMF) Sculpts Microtubules.The European journal of neuroscience · 2025Article
- Hyperhomocysteinemia Is Associated With a Myriad of Age-Related Illnesses: A Potential Role for Metal Toxicity.Mayo Clinic proceedings · 2024Article
- Copper(II), Nickel(II) and Zinc(II) Complexes of Peptide Fragments of Tau Protein.Molecules (Basel, Switzerland) · 2024Article
- The Role of Liquid-Liquid Phase Separation in the Accumulation of Pathological Proteins: New Perspectives on the Mechanism of Neurodegenerative Diseases.Aging and disease · 2024Review
- Molecular Mechanism of Tau Misfolding and Aggregation: Insights from Molecular Dynamics Simulation.Current medicinal chemistry · 2024Review
- Treatment with 1, 10 Phenanthroline-5-Amine Reduced Amyloid Burden in a Mouse Model of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- Aggregation, Transmission, and Toxicity of the Microtubule-Associated Protein Tau: A Complex Comprehension.International journal of molecular sciences · 2023Review
- Zn2+ decoration of microtubules arrests axonal transport and displaces tau, doublecortin, and MAP2C.The Journal of cell biology · 2023Article
- Zinc and Central Nervous System Disorders.Nutrients · 2023Review
- Zinc Homeostasis: An Emerging Therapeutic Target for Neuroinflammation Related Diseases.Biomolecules · 2023Review
- Development of fluorophores for the detection of oligomeric aggregates of amyloidogenic proteins found in neurodegenerative diseases.Frontiers in chemistry · 2023Review
- Toxicities of amyloid-beta and tau protein are reciprocally enhanced in theNeural regeneration research · 2022Article
- Aβ and Tau Interact with Metal Ions, Lipid Membranes and Peptide-Based Amyloid Inhibitors: Are These Common Features Relevant in Alzheimer's Disease?Molecules (Basel, Switzerland) · 2022Review
- Emodin Protects SH-SY5Y Cells Against Zinc-Induced Synaptic Impairment and Oxidative Stress Through the ERK1/2 Pathway.Frontiers in pharmacology · 2022Article
- Intra-articular injection of clioquinol ameliorates osteoarthritis in a rabbit model.Frontiers in medicine · 2022Article
- Clioquinol Decreases Levels of Phosphorylated, Truncated, and Oligomerized Tau Protein.International journal of molecular sciences · 2021Article
- NEUROTOXICITY OF METAL MIXTURES.Advances in neurotoxicology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Tau hyperphosphorylation is thought to underlie tauopathy. Working in a Drosophila tauopathy model expressing a human Tau mutant (hTauR406W, or Tau(∗)), we show that zinc contributes to the development of Tau toxicity through two independent actions: by increasing Tau phosphorylation and, more significantly, by directly binding to Tau. Elimination of zinc binding through amino acid substitution of Cys residues has a minimal effect on phosphorylation levels yet essentially eliminates Tau toxicity. The toxicity of the zinc-binding-deficient mutant Tau(∗) (Tau(∗)C2A) and overexpression of native Drosophila Tau, also lacking the corresponding zinc-binding Cys residues, are largely impervious to zinc concentration. Importantly, restoration of zinc-binding ability to Tau(∗) by introduction of a zinc-binding residue (His) into the original Cys positions restores zinc-responsive toxicities in proportion to zinc-binding affinities. These results indicate zinc binding is a substantial contributor to tauopathy and have implications for therapy development.
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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.