ArticleNature chemical biology2018
Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system.
Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 161 citations in OpenAlex.
- Copper import via CTR1 supports the β3-Adrenergic thermogenic program.Molecular metabolism · 2026Article
- Review
- Copper homeostasis and cuproptosis in cancer: mitochondrial metabolic dependency and nanomedicine-based therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026Review
- Cuproptosis inducers mediate cold lethality via SLCR-46.1 in C. elegans.Nature communications · 2026Article
- Temperature Dependence of Paramagnetic Species in the Human Brain Tissue: An X-Band EPR Study.Magnetic resonance in medicine · 2026Article
- An Activity-Based Sensing Approach to Monitor Nanomaterial-Promoted Changes in Labile Metal Pools in Living Systems.Chemical & biomedical imaging · 2026Article
- Copper deficiency impairs oligodendrocyte maturation and social behavior via mitophagy and mTOR suppression in ASD.Science advances · 2026Article
- Human serum albumin-derived biosensor for visualizing copper(II) and hydrogen sulfide interactions in cancer cells.Journal of advanced research · 2026Article
- Copper Import via CTR1 Supports the β3-Adrenergic Thermogenic Program.bioRxiv : the preprint server for biology · 2026Article
- Repurposing melatonin's therapeutic potential in Wilson disease: Addressing copper overload and redox imbalance.Redox biology · 2026Article
- Cuproptosis: Biomarkers, Mechanisms and Treatments in Diseases.Molecules (Basel, Switzerland) · 2026Review
- Harnessing copper: Innovative approaches to combat neurodegenerative diseases and cancer (Review).International journal of molecular medicine · 2026Review
- Copper homeostasis and cuproptosis in Alzheimer's disease (Review).International journal of molecular medicine · 2025Review
- An Alkyne-Directed Cleavage Approach for Activity-Based Cu(I) Sensing Reveals Manganese-Promoted Sensitization of Cuproptosis.Journal of the American Chemical Society · 2025Article
- RAD23B acquires a copper metalloadaptor function in amphibian-to-reptile evolution to increase metabolism and regulate genomic integrity.Molecular cell · 2025Article
- Signal Transduction Strategies for DNAzyme-Based Sensing and Imaging of Metal Ions in Cells andChemical & biomedical imaging · 2025Review
- A primer on copper biology in the brain.Neurobiology of disease · 2025Review
- Catalysis in Chemical Modification of Proteins.ChemCatChem · 2025Article
- A Self-Immobilizing Photoacoustic Probe for Ratiometric In Vivo Imaging of Cu(II) in Tumors.Chemical & biomedical imaging · 2025Article
- Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment.Cancer cell international · 2025Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The unusually high demand for metals in the brain, along with insufficient understanding of how their dysregulation contributes to neurological diseases, motivates the study of how inorganic chemistry influences neural circuitry. We now report that the transition metal copper is essential for regulating rest-activity cycles and arousal. Copper imaging and gene expression analysis in zebrafish identifies the locus coeruleus-norepinephrine (LC-NE) system, a vertebrate-specific neuromodulatory circuit critical for regulating sleep, arousal, attention, memory and emotion, as a copper-enriched unit with high levels of copper transporters CTR1 and ATP7A and the copper enzyme dopamine β-hydroxylase (DBH) that produces NE. Copper deficiency induced by genetic disruption of ATP7A, which loads copper into DBH, lowers NE levels and hinders LC function as manifested by disruption in rest-activity modulation. Moreover, LC dysfunction caused by copper deficiency from ATP7A disruption can be rescued by restoring synaptic levels of NE, establishing a molecular CTR1-ATP7A-DBH-NE axis for copper-dependent LC function.
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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.