Do glutathione and copper interact to modify Alzheimer's disease pathogenesis?

Ho, Talia; Ahmadi, Soha; Kerman, Kağan

doi:10.1016/j.freeradbiomed.2022.01.025

Cited by 14 publications

(8 citation statements)

References 230 publications

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“…53 Interaction of Cu with Aβ in senile plaques is also a reason for the formation and stabilization of Aβ aggregates. 52,54 Additionally, freely available Cu and Fe can effectively catalyze the generation of ROS through the Fenton reaction. 42 Both Fe 2+ and Cu + can react with H 2 O 2 and generate OH − and • OH, both highly reactive radicals.…”

Section: Acsmentioning

confidence: 99%

“…Additionally, the amyloid precursor protein (APP) has a Cu-binding site and binding of Cu to this site leads to oxidative modification of the APP. , The binding of Cu 2+ to APP reduces it to Cu + , giving rise to ROS such as O 2 •– or • OH . Interaction of Cu with Aβ in senile plaques is also a reason for the formation and stabilization of Aβ aggregates. , Additionally, freely available Cu and Fe can effectively catalyze the generation of ROS through the Fenton reaction . Both Fe 2+ and Cu + can react with H 2 O 2 and generate OH – and • OH, both highly reactive radicals.…”

Section: Introductionmentioning

confidence: 99%

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Oxidative Stress Occurs Prior to Amyloid Aβ Plaque Formation and Tau Phosphorylation in Alzheimer’s Disease: Role of Glutathione and Metal Ions

Roy

Mandal

Maroon

2023

ACS Chem. Neurosci.

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Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disorder that affects millions of people worldwide. Although the pathogenesis remains obscure, there are two dominant causal hypotheses. Since last three decades, amyloid beta (Aβ) deposition was the most prominent hypothesis, and the other is the tau hyperphosphorylation hypothesis. The confirmed diagnostic criterion for AD is the presence of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau and the deposition of toxic oligomeric Aβ in the autopsied brain. Consistent with these hypotheses, oxidative stress (OS) is garnering major attention in AD research. OS results from an imbalance of pro-oxidants and antioxidants. There is a considerable debate in the scientific community on which process occurs first, OS or plaque deposition/tau hyperphosphorylation. Based on recent scientific observations of various laboratories including ours along with critical analysis of those information, we believe that OS is the early event that leads to oligomeric Aβ deposition as well as dimerization of tau protein and its subsequent hyperphosphorylation. This OS hypothesis immediately suggests the consideration of novel therapeutic approaches to include antioxidants involving glutathione enrichment in the brain by supplementation with or without an iron chelator.

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Section: Acsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxidative Stress Occurs Prior to Amyloid Aβ Plaque Formation and Tau Phosphorylation in Alzheimer’s Disease: Role of Glutathione and Metal Ions

Roy

Mandal

Maroon

2023

ACS Chem. Neurosci.

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“…Glutathione, an endogenous copper chelator, also participates in TCA. Depletion of glutathione will change copper levels and trigger cuproptosis [ 31 ]. Although copper ionophores and copper chelators have been demonstrated to be anticancer agents, the lack of alternatives is still a major challenge.…”

Section: Copper and Cuproptosismentioning

confidence: 99%

Role of cuproptosis in understanding diseases

Cao,

Wang,

Sun

et al. 2023

Human Cell

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Cell death is involved in a wide range of physiological and pathological processes. Recently, the term “cuproptosis” was coined to describe a novel type of cell death. This type of cell death, characterized by copper accumulation and proteotoxic stress, is a copper-dependent manner of death. Despite the progress achieved toward a better understanding of cuproptosis, mechanisms and related signaling pathways in physiology and pathology across various diseases remain to be proved. This mini review summarizes current research on cuproptosis and diseases, providing insights into prospective clinical therapies via targeting cuproptosis.

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“…However, several studies have reported that CQ does not exhibit a significant advantage over alternative chelators in effectively treating AD (Adlard et al, 2008;Sun et al, 2022). Furthermore, clinical trials of CQ for AD have been unsuccessful (Ho et al, 2022). 5,7-Dichloro-2-(dimethylamino)methyl-8-hydroxyquinoline (PBT2) is a second-generation derivative of 8-OH quinoline (Lannfelt et al, 2008) that has been developed as an ion carrier (Bush, 2008;Cahoon, 2009).…”

Section: Potential Therapeutic Avenues 41 Copper Chelatorsmentioning

confidence: 99%

“…Reports have stated that p53 can inhibit glucose uptake and glycolysis, promoting a metabolic shift in the TCA cycle and oxidative phosphorylation and contributing to Cu toxicity (Li et al, 2023;Xiong et al, 2023). In addition, p53 regulates the biogenesis of Fe-S clusters and glutathione (GSH) (Ho et al, 2022;Xiong et al, 2023), thereby mitigating or enhancing Cu toxicity (Xiong et al, 2023)-two processes crucial for cuproptosis. Thus, p53-related therapeutic targets could be associated with cuproptosis, although its detailed mechanism of regulating Cu toxicity requires further research.…”

Section: Other Therapeutic Targetsmentioning

confidence: 99%

Copper and cuproptosis: new therapeutic approaches for Alzheimer’s disease

Li,

Chen,

Gao

2023

Front. Aging Neurosci.

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Copper (Cu) plays a crucial role as a trace element in various physiological processes in humans. Nonetheless, free copper ions accumulate in the brain over time, resulting in a range of pathological changes. Compelling evidence indicates that excessive free copper deposition contributes to cognitive decline in individuals with Alzheimer’s disease (AD). Free copper levels in the serum and brain of AD patients are notably elevated, leading to reduced antioxidant defenses and mitochondrial dysfunction. Moreover, free copper accumulation triggers a specific form of cell death, namely copper-dependent cell death (cuproptosis). This article aimed to review the correlation between copper dysregulation and the pathogenesis of AD, along with the primary pathways regulating copper homoeostasis and copper-induced death in AD. Additionally, the efficacy and safety of natural and synthetic agents, including copper chelators, lipid peroxidation inhibitors, and antioxidants, were examined. These treatments can restore copper equilibrium and prevent copper-induced cell death in AD cases. Another aim of this review was to highlight the significance of copper dysregulation and promote the development of pharmaceutical interventions to address it.

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Do glutathione and copper interact to modify Alzheimer's disease pathogenesis?

Cited by 14 publications

References 230 publications

Oxidative Stress Occurs Prior to Amyloid Aβ Plaque Formation and Tau Phosphorylation in Alzheimer’s Disease: Role of Glutathione and Metal Ions

Oxidative Stress Occurs Prior to Amyloid Aβ Plaque Formation and Tau Phosphorylation in Alzheimer’s Disease: Role of Glutathione and Metal Ions

Role of cuproptosis in understanding diseases

Copper and cuproptosis: new therapeutic approaches for Alzheimer’s disease

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