Copper Induces Cognitive Impairment in Mice via Modulation of Cuproptosis and CREB Signaling

Nutrients, Journal Year: 2023, Volume and Issue: 15(4), P. 972 - 972

Published: Feb. 15, 2023

It has been reported that disordered Cu metabolism is associated with several neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's (PD). However, the underlying mechanism still unclear. In this study, 4-week-old male mice were exposed to by free-drinking water for three months. Then, effects of on cognitive functions in tested Morris maze tests, potential mechanisms investigated ELISA, immunochemistry, TUNEL, Western blot tests. was found exacerbates learning memory impairment, leads Cu-overload brain urine mice. The results showed induces neuronal degeneration oxidative damage, promotes expression apoptosis-related protein Bax, cuproptosis-related proteins FDX1 DLAT proteotoxic stress marker HSP70, decreases Fe-S cluster proteins. addition, affects pre-synaptic post-synaptic regulatory through inhibiting PSD-95 SYP. also suppresses phosphorylation levels CREB BDNF TrkB mouse hippocampus. conclusion, might mediate cuproptosis, damage synaptic plasticity inhibit CREB/BDNF pathway cause dysfunction

Language: Английский

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Copper homeostasis and cuproptosis in mitochondria

Life Sciences, Journal Year: 2023, Volume and Issue: 334, P. 122223 - 122223

Published: Oct. 29, 2023

Language: Английский

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Recent Advances in Cancer Therapeutic Copper-Based Nanomaterials for Antitumor Therapy

Molecules, Journal Year: 2023, Volume and Issue: 28(5), P. 2303 - 2303

Published: March 1, 2023

Copper serves as a vital microelement which is widely present in the biosystem, functioning multi-enzyme active site, including oxidative stress, lipid oxidation and energy metabolism, where reduction characteristics are both beneficial lethal to cells. Since tumor tissue has higher demand for copper more susceptible homeostasis, may modulate cancer cell survival through reactive oxygen species (ROS) excessive accumulation, proteasome inhibition anti-angiogenesis. Therefore, intracellular attracted great interest that multifunctional copper-based nanomaterials can be exploited diagnostics antitumor therapy. this review explains potential mechanisms of copper-associated death investigates effectiveness biomaterials field

Language: Английский

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Neurotoxic effects of heavy metal pollutants in the environment: Focusing on epigenetic mechanisms

Environmental Pollution, Journal Year: 2024, Volume and Issue: 345, P. 123563 - 123563

Published: Feb. 13, 2024

Language: Английский

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Cellular and molecular mechanisms of cell damage and cell death in ischemia–reperfusion injury in organ transplantation

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: March 29, 2024

Ischemia-reperfusion injury (IRI) is a critical pathological condition in which cell death plays major contributory role, and negatively impacts post-transplant outcomes. At the cellular level, hypoxia due to ischemia disturbs metabolism decreases bioenergetics through dysfunction of mitochondrial electron transport chain, causing switch from respiration anaerobic metabolism, subsequent cascades events that lead increased intracellular concentrations Na

Language: Английский

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Cuproptosis and copper as potential mechanisms and intervention targets in Alzheimer's disease

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117814 - 117814

Published: Jan. 13, 2025

Language: Английский

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The Molecular Mechanisms of Defective Copper Metabolism in Diabetic Cardiomyopathy

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 16

Published: Oct. 4, 2022

Copper is an essential trace metal element that significantly affects human physiology and pathology by regulating various important biological processes, including mitochondrial oxidative phosphorylation, connective tissue crosslinking, antioxidant defense. level has been proved to be closely related the morbidity mortality of cardiovascular diseases such as atherosclerosis, heart failure, diabetic cardiomyopathy (DCM). deficiency can induce cardiac hypertrophy aggravate cardiomyopathy, while copper excess mediate types cell death, autophagy, apoptosis, cuproptosis, pyroptosis, fibrosis. Both lead redox imbalance, activate inflammatory response, cardiomyopathy. This defective metabolism suggests a specific metabolic pattern in diabetes role pathogenesis progression DCM. review aimed at providing timely summary effects homeostasis on DCM discussing potential underlying molecular mechanisms.

Language: Английский

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Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1

Annals of Medicine, Journal Year: 2023, Volume and Issue: 55(1)

Published: May 10, 2023

Excessive oxygen free radicals and toxic substances are generated in cerebral ischemia-reperfusion (I/R) process. Dexmedetomidine (DEX), a common anesthetic sedative drug, can considerably boost glutathione (GSH), which has anti-copper influx effects. Focusing on cuproptosis, the mechanism of DEX I/R was revealed. Using rat model, effects copper chelator D-penicillamine infarct volume, levels, mitochondrial respiration membrane potential, GSH content, enrichment cuproptosis functional proteins were examined. The involvement ferredoxin 1 (FDX1) regulatory pathway verified by overexpressing FDX1 vitro. could significantly reduce infarction rats, maintain functions, increase GSH, content key related to cuproptosis. These aspects replicated vitro revealed that overexpression partially reversed impacts DEX. Together, occurs brain process enhance cell survival blocking primary mediated FDX1.KEY MESSAGESDexmedetomidine reduces models.Dexmedetomidine models.FDX1, an upstream protein fatty acylation, mediates regulation Dexmedetomidine.

Language: Английский

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Oxygen metabolism abnormality and Alzheimer's disease: An update

Redox Biology, Journal Year: 2023, Volume and Issue: 68, P. 102955 - 102955

Published: Nov. 8, 2023

Oxygen metabolism abnormality plays a crucial role in the pathogenesis of Alzheimer's disease (AD) via several mechanisms, including hypoxia, oxidative stress, and mitochondrial dysfunction. Hypoxia condition usually results from living high-altitude habitat, cardiovascular cerebrovascular diseases, chronic obstructive sleep apnea. Chronic hypoxia has been identified as significant risk factor for AD, showing an aggravation various pathological components such amyloid β-protein (Aβ) metabolism, tau phosphorylation, dysfunction, neuroinflammation. It is known that excessive hyperoxia can both result stress Oxidative dysfunction increase Aβ proteins lead to redox imbalance, thus forming vicious cycle exacerbating AD pathology. Hyperbaric oxygen therapy (HBOT) non-invasive intervention its capacity significantly enhance cerebral oxygenation levels, which attenuate aggregation, However, further investigation imperative determine optimal pressure, duration exposure, frequency HBOT sessions. In this review, we explore prospects with aim enhancing our understanding underlying molecular mechanisms AD. Current research aimed at attenuating abnormalities holds promise providing novel therapeutic approaches

Language: Английский

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Heavy Metal Mediated Progressive Degeneration and Its Noxious Effects on Brain Microenvironment

Biological Trace Element Research, Journal Year: 2023, Volume and Issue: 202(4), P. 1411 - 1427

Published: July 18, 2023

Language: Английский

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