Copper and Heme-Mediated Abeta Toxicity: Redox Chemistry, Abeta Oxidations and Anti-ROS Compounds

Chassaing, Stefan; Collin, Fabrice; Dorlet, Pierre; Gout, Jérôme; Hureau, Christelle; Faller, Peter

doi:10.2174/15680266112129990080

Cited by 12 publications

(24 citation statements)

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“…Redox active metal ions play a key role in oxidative stress, either in the production of ROS/RNS by enzymes or loosely bound metals or in the protection against ROS, mostly as catalytic centers in enzymes. In AD, it is thought that metals (mostly Cu, Fe and heme) can bind to Aβ and that such systems are involved in the generation of oxidative stress (Chassaing et al, 2012).…”

Section: Amyloid Beta (Aß or Abeta)mentioning

confidence: 99%

Title: Biochemical linkage of type 2 diabetes mellitus and Alzheimer’s disease

Mahmoud

Abo-Elmatty

Mesbah

et al. 2019

Records of Pharmaceutical and Biomedical Sciences

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Type 2 diabetes mellitus (T2DM) is a common disease in the elderly, affecting around 20% of geriatrics. In cross-sectional studies, T2DM had various adverse health effects, including cognitive impairment. The association of T2DM with decreased cognitive function suggests that T2DM can contribute to Alzheimer's disease (AD) The relationship between T2DM and AD continues to grow rapidly. It has been suggested that AD can be considered "type 3 diabetes". Along with the processing of amyloid precursor protein (APP) and tau phosphorylation, the molecular links between T2DM and AD provide clues for new therapeutic targets such as glucagon-like peptide-1 (GLP-1), butyrylcholinesterase and receptor for advanced glycosylation end products (AGE). A possible mechanism correlating T2DM and AD is the alteration in insulin signaling in the brain. Insulin signaling is involved in several neuronal functions, and plays a vital role in the pathophysiology of AD. Therefore, the modification of neuronal insulin signaling by diabetic conditions may contribute to AD progression. Another possible mechanism is cerebrovascular changes, a common pathological change observed in both diseases. The importance of amyloid beta peptide (Aβ) induced cerebrovascular dysfunction in AD has been reported, indicating that pathological interactions between AGE receptor and Aβ have a role in this disorder.

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Section: Amyloid Beta (Aß or Abeta)mentioning

confidence: 99%

Title: Biochemical linkage of type 2 diabetes mellitus and Alzheimer’s disease

Mahmoud

Abo-Elmatty

Mesbah

et al. 2019

Records of Pharmaceutical and Biomedical Sciences

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“…Oxidative stress, which can be defined as the consequence of an imbalance between pro-oxidants and defence systems (antioxidants, enzymes), resulting in (often irreversible) if ROS is a cause or a consequence of the disease. 38 The toxicity of Aβ to neurons is related to the production of ROS. 39 In this sense, the addition of the H2O2 scavenging catalase [40][41][42] or synthetic catalytic free radical scavenger 43 inhibits the Aβ toxicity towards cells in culture.…”

Section: Reactive Oxygen Species Induced Oxidative Stressmentioning

confidence: 99%

“…Thus, there would be no need for a dimeric Cu center and monomeric Cu-Aβ would be sufficient to catalyze these reactions. 2,38 Regarding the biological consequences, the potential role of Cu-Aβ as a catalyst in the context of oxidative stress have been extended, given that Cu-Aβ would not be only able to generate H2O2 and HO • , but also O2 •-. Additionally, the production of O2 •can lead to very deleterious species, in particular peroxynitrite whose role in neurodegenerative diseases has been reviewed.…”

Section: Cu-aβ and Ros Productionmentioning

confidence: 99%

“…These values are in the range of spontaneous dismutation (~10 5 M -1 s -1 at pH 7) and at least 10 3 times slower than that of superoxide dismutase, and hence likely of little biological relevance. 38 At low ascorbate concentrations (<100 μM), the rate of ascorbate oxidation reaction by O2 mediated 58 It is worth pointing out that the rate of ascorbate oxidation catalyzed by the enzyme ascorbate oxidase is 1.7 10 4 M -1 s -1 . Thus, the reaction rates obtained for the ascorbate oxidation by O2 mediated by Cu-Aβ are moderately high.…”

Section: Efficiency and Biological Relevance Of The Ros Production Bymentioning

confidence: 99%

“…In general, the activity of Cu-Aβ seems to be intermediate as the efficiency is below enzymes that catalyze ascorbate oxidation 58 or H2O2 production 59 , but Cu-Aβ produces more than biologically relevant Cu-peptides/proteins tested, such as metallothionein and human serum albumin. 38,60 Nevertheless, anti-oxidant properties were also proposed for the monomeric form of Aβ, 61 as well as dual role. 62 In vitro studies support the pro-oxidant role of Cu-Aβ complex.…”

Section: Efficiency and Biological Relevance Of The Ros Production Bymentioning

confidence: 99%

See 2 more Smart Citations

Metal-Binding to Amyloid-β Peptide: Coordination, Aggregation, and Reactive Oxygen Species Production

Barrio

Borghesani

Hureau

et al. 2017

Biometals in Neurodegenerative Diseases

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Amyloid-plaques are a hallmark of Alzheimer's disease. They consist mainly of an aggregated peptide called amyloid-β. These plaques also accumulate high concentrations of metal ions, mainly Cu, Zn and Fe. Cu and Zn directly bind to amyloid-β in vivo. This triggered a strong research activity in order to understand the biology and chemistry of the interaction between metal ions and amyloid-β. This includes also the chemical and biophysical aspects of the metal-amyloid-β complexes. The present article describes the coordination chemistry of the Cu(II), Cu(I), Zn(II) and Fe(II) complexes in terms of ligand spheres and affinities. Moreover, metal ions modulate the selfassembly of amyloid-β into amyloids, a central event in Alzheimer's disease. Attention was paid on the catalytic role of Cu-bound to amyloid-β, in particular in terms of the production of reactive oxygen species, which have been proposed to be involved in the disease progression. Recent mechanistic insights are described.

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On the ability of CuAβ1-x peptides to form ternary complexes: Neurotransmitter glutamate is a competitor while not a ternary partner

Frączyk

Zawisza

Goch

et al. 2016

Journal of Inorganic Biochemistry

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In the light of conflicting reports on the ability of copper(II) complexes of amyloid beta (Aβ) peptides to form ternary complexes with small molecules co-present in the biological milieu, we performed a study of coordination equilibria in the system containing Cu(II) ions, the Aβ1-16 peptide, glutamic acid and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid, HEPES) buffer. Using potentiometry, isothermal titration calorimetry (ITC), UV-visible spectroscopy and EPR, we concluded that glutamic acid was not able to form such a ternary complex, but can efficiently compete for the Cu(II) ion with the Aβ peptide at Glu concentrations relevant for the synaptic cleft. We also found that the literature constants for Cu(II) complexes with Glu were overestimated, but this effect was partially compensated by the formation of a ternary Cu(Glu)(HEPES) complex. Our results indicate that small molecules co-present with Cu(II) ions and Aβ peptides in the synaptic cleft are not very likely to enhance Cu(II)/Aβ interactions, but instead should be considered as a Cu(II) buffering system that may help prevent these interactions and participate in Cu(II) clearance from the synaptic cleft.

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Copper and Heme-Mediated Abeta Toxicity: Redox Chemistry, Abeta Oxidations and Anti-ROS Compounds

Cited by 12 publications

References 0 publications

Title: Biochemical linkage of type 2 diabetes mellitus and Alzheimer’s disease

Title: Biochemical linkage of type 2 diabetes mellitus and Alzheimer’s disease

Metal-Binding to Amyloid-β Peptide: Coordination, Aggregation, and Reactive Oxygen Species Production

On the ability of CuAβ1-x peptides to form ternary complexes: Neurotransmitter glutamate is a competitor while not a ternary partner

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