ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Copper Exposure Perturbs Brain Inflammatory Responses and Impairs Clearance of Amyloid-Beta.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 2 of them syntheses that pooled it.
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Who cites it
70 citing papers in PubMed, 2 syntheses or guidelines pooled it, 126 citations in OpenAlex.
- Mechanisms and Pathogenesis of Diabetic Cognitive Impairment: A Comprehensive Review.Aging and disease · 2025Pooled it
- Cuproptosis as a therapeutic target in cancer: a Systematic Review and bibliometric analysis of the research landscape.Frontiers in oncology · 2025Pooled it
- Metallothionein and neurodegenerative diseases.Neural regeneration research · 2026Article
- Review
- The mechanisms and strategies for Alzheimer's disease prevention: An update.Acta pharmaceutica Sinica. B · 2026Review
- Agricultural Copper Pesticide Exposure and Metabolic Profiles among Parkinson's Disease Cases and Community Controls in California.Chemical research in toxicology · 2026Article
- Cuproptosis-associated genesFrontiers in immunology · 2026Article
- Copper Homeostasis and Cuproptosis in Neurological Disorders.Drug design, development and therapy · 2026Review
- Elucidating molecular mechanisms governing tumor necrosis factor-alpha-mediated regulation of amyloid beta 42 uptake in blood-brain barrier endothelial cells.Molecular pharmacology · 2026Article
- Agricultural copper pesticide exposure and DNA methylation in Central Valley of California residents with and without Parkinson's disease.Environmental research · 2025Article
- Copper homeostasis and cuproptosis in Alzheimer's disease (Review).International journal of molecular medicine · 2025Review
- Copper regulates the expression of immune genes in microglial cells in vitro.Immunobiology · 2025Article
- Endothelial cell-derived apoptotic bodies modulate innate and adaptive immune responses during inflammation.Cell communication and signaling : CCS · 2025Article
- Unraveling the Vicious Cycle: Oxidative Stress and Neurotoxicity in Neurodegenerative Diseases.FASEB bioAdvances · 2025Review
- Identifying the important involvement of cuproptosis in the pathophysiology of age-related macular degeneration.European journal of medical research · 2025Article
- Lavandula angustifolia and Cyperus rotundus Extract Treatments Ameliorate Copper Toxicity in Rats.Brain and behavior · 2025Article
- Particulate matter and co-occurring genetic risk induce oxidative stress and cardiac and brain Alzheimer's pathology.Communications biology · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Cinobufagin treatments suppress tumor growth by enhancing the expression of cuproptosis-related genes in liver cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Copper promotes a toxic buildup of amyloid-beta (Aβ) and neurofibrillary tangle pathology in the brain, and its exposure may increase the risk for Alzheimer's disease (AD). However, underlying molecular mechanisms by which copper triggers such pathological changes remain largely unknown. We hypothesized that the copper exposure perturbs brain inflammatory responses, leading to impairment of Aβ clearance from the brain parenchyma. Here, we investigated whether copper attenuated Aβ clearance by microglial phagocytosis or by low-density lipoprotein-related receptor protein-1 (LRP1) dependent transcytosis in both in vitro and in vivo When murine monocyte BV2 cells were exposed to copper, their phagocytic activation induced by fibrillar Aβ or LPS was significantly reduced, while the secretion of pro-inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, were increased. Interestingly, not only copper itself but also IL-1β, IL-6, or TNF-α were capable of markedly reducing the expression of LRP1 in human microvascular endothelial cells (MVECs) in a concentration-dependent manner. While copper-mediated downregulation of LRP1 was proteasome-dependent, the cytokine-induced loss of LRP1 was proteasome- or lysosome-independent. In the mouse model, copper exposure also significantly elevated neuroinflammation and downregulated LRP1 in the brain, consistent with our in vitro results. Taken together, our findings support the pathological impact of copper on inflammatory responses and Aβ clearance in the brain, which could serve as key mechanisms to explain, in part, the copper exposure as an environmental risk factor for AD.
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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.