ArticleVascular pharmacology2024
Altered copper transport in oxidative stress-dependent brain endothelial barrier dysfunction associated with Alzheimer's disease.
Article in Vascular pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Cuproptosis in spinal cord injury: emerging mechanisms and immunological relevance.Annals of medicine · 2026Review
- Cellular and subcellular localization of the copper transporter CTR1 in human postmortem hippocampus and striatum.Scientific reports · 2026Article
- Cuproptosis: Biomarkers, Mechanisms and Treatments in Diseases.Molecules (Basel, Switzerland) · 2026Review
- Roles of cuproptosis in central nervous system tumors: from molecular mechanisms to therapeutic prospects.Frontiers in cell and developmental biology · 2026Review
- Silencing SLC31A1 attenuates high glucose plus copper-induced cuproptosis-like signaling, oxidative stress, and barrier dysfunction in human retinal microvascular endothelial cells.International journal of ophthalmology · 2026Article
- The gut-liver-kidney-brain axis in Wilson disease: copper speciation-flux and barrier-mediated organ crosstalk.Frontiers in immunology · 2026Review
- Emerging Roles of Regulated Cell Death-mediated Inflammation in Pathophysiology of Ocular Diseases.Journal of ophthalmic & vision research · 2026Review
- Novel Role of Copper Transporter CTR1 and Therapeutic Potential of Copper Chelators in Retinal Ischemia-Reperfusion Injury.Investigative ophthalmology & visual science · 2025Article
- Endothelial ENaC as a repressor of oxidative stress and a guardian of lung capillary barrier function in bacterial and viral pneumonia.Frontiers in physiology · 2025Review
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Abstract
Oxidative stress and blood-brain barrier (BBB) disruption due to brain endothelial barrier dysfunction contribute to Alzheimer's Disease (AD), which is characterized by beta-amyloid (Aβ) accumulation in senile plaques. Copper (Cu) is implicated in AD pathology and its levels are tightly controlled by several Cu transport proteins. However, their expression and role in AD, particularly in relation to brain endothelial barrier function remains unclear. In this study, we examined the expression of Cu transport proteins in the brains of AD mouse models as well as their involvement in Aβ42-induced brain endothelial barrier dysfunction. We found that the Cu uptake transporter CTR1 was upregulated, while the Cu exporter ATP7A was downregulated in the hippocampus of AD mouse models and in Aβ42-treated human brain microvascular endothelial cells (hBMECs). In the 5xFAD AD mouse model, Cu levels (assessed by ICP-MS) were elevated in the hippocampus. Moreover, in cultured hBMECs, Aβ42-induced reactive oxygen species (ROS) production, ROS-dependent loss in barrier function (measured by transendothelial electrical resistance), and tyrosine phosphorylation of CDH5 were all inhibited by either a membrane permeable Cu chelator or by knocking down CTR1 expression. These findings suggest that dysregulated expression of Cu transport proteins may lead to intracellular Cu accumulation in the AD brain, and that Aβ42 promotes ROS-dependent brain endothelial barrier dysfunction and CDH5 phosphorylation in a CTR1-Cu-dependent manner. Our study uncovers the critical role of Cu transport proteins in oxidative stress-related loss of BBB integrity in AD.
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