Interaction of Metal Ions with the His13-His14 Sequence Relevant to Alzheimer’s Disease

Kong, Xiangtao; Zhao, Zijian; Lei, Xiaoguang; Zhang, Bingbing; Dai, Dongxu; Jiang, Ling

doi:10.1021/acs.jpca.5b01443

Cited by 9 publications

(4 citation statements)

References 75 publications

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“…There are a number of different mechanisms through metal ions can aggravate AD [41]. By the interaction of metal ions with peptides, the conformation of peptide suffers some modifications with the formation of peptide-metal complexes with or without aggregation and peptide fibril formation [42].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Different Analogs of Ab(9-16) Peptide Mass spectrometric evidence for heavy metal binding

Jureschi¹,

Petre²,

Ion³

et al. 2019

Rev. Chim.

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Amyloid-b (Ab) peptides are proteins associated with Alzheimer�s disease (AD), because the extracellular Ab deposits are the main cause of this disorder. The aggregation of Ab has been shown to depend on the interactions with metal ions, such as copper, zinc, aluminum or iron. The N-terminal sequence of Ab(1-42) or Ab(1-40) peptides, namely Ab(1-16) peptide fragment, is considered the metal binding site involved in AD neurodegeneration and amyloidogenesis. Therefore, we have investigated different peptide sequences to understand the role played by some amino acid residues in metal binding. In this paper, we report the chemical synthesis of Ab(9-16) peptide and its analogs by Fmoc/tBu strategy and the mass spectrometric evidence for metal ion binding to newly synthesized peptides. MALDI-ToF mass spectrometry proved to be a reliable tool to detect and identify the metal ion complexes of all peptides investigated with copper, iron and zinc ions.

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Section: Resultsmentioning

confidence: 99%

Synthesis of Different Analogs of Ab(9-16) Peptide Mass spectrometric evidence for heavy metal binding

Jureschi¹,

Petre²,

Ion³

et al. 2019

Rev. Chim.

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“…96,97 Cu-Aβ model systems that consider copper cation and its coordination sphere have been used to study copper preferences in the Aβ sequence and to propose plausible mechanisms to the reactions that increase oxidative stress. 98,99 Recently, Bertini et al have used density functional theory (DFT) methods to study the mechanism of the O 2 reduction to OH − + •OH radical mediated by Cu-Aβ model systems and ascorbate. 100 As has been pointed out, the use of small model systems has allowed the understanding of copper coordination and reactivity of Cu-Aβ complexes.…”

Section: 1mentioning

confidence: 99%

Role of Metal Cations of Copper, Iron, and Aluminum and Multifunctional Ligands in Alzheimer’s Disease: Experimental and Computational Insights

et al. 2023

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Alzheimer’s disease (AD) is the most common form of dementia, affecting millions of people around the world. Even though the causes of AD are not completely understood due to its multifactorial nature, some neuropathological hallmarks of its development have been related to the high concentration of some metal cations. These roles include the participation of these metal cations in the production of reactive oxygen species, which have been involved in neuronal damage. In order to avoid the increment in the oxidative stress, multifunctional ligands used to coordinate these metal cations have been proposed as a possible treatment to AD. In this review, we present the recent advances in experimental and computational works aiming to understand the role of two redox active and essential transition-metal cations (Cu and Fe) and one nonbiological metal (Al) and the recent proposals on the development of multifunctional ligands to stop or revert the damaging effects promoted by these metal cations.

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“…For these reasons, a number of techniques have been employed to determine the amino acids involved in the recognition of metals by Aβ. It is generally accepted that metal ions are bound to the histidine residues at positions 6, 13, and 14 [56]. Several studies have demonstrated that the interaction of Cu 2+ , Zn 2+ , Fe 3+ , and Al 3+ with Aβ is maintained by their coordination with His13-His14 of the peptide.…”

Section: Interaction Of Metals With Amyloid Beta and Hydrogen Peroxidmentioning

confidence: 99%

Involvement of Free Radicals in the Development and Progression of Alzheimer’s Disease

Rosales‐Hernández¹,

Rodríguez²,

Correa-Basurto³

2016

Free Radicals and Diseases

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Alzheimer's disease (AD) is a major dementia related to an overproduction of free radicals (FRs), which leads to the generation of oxidative stress in brain tissue. Amyloid beta-peptide of 42 amino acid residues (Aβ 1-42) is the main source of FRs in patients with AD. βA 1-42 results from hydrolysis of the amyloid precursor protein by β-secretase in a process known as the amyloidogenic pathway. During βA 1-42 aggregation, the peptide interacts with various transition metals to produce hydrogen peroxide (H 2 O 2) by the Fenton reaction, generating the hydroxyl radical (• OH), which damages lipids, proteins, and nucleic acids, thereby contributing to neurodegeneration. In addition, βA 1-42 is recognized by microglial receptors; it activates these cells, causing overproduction of superoxide anion (O 2 •−) by NADPH oxidase; O 2 •− is also converted into H 2 O 2 and finally to • OH in the Fenton reaction. Other factors that contribute to oxidative stress during microglial activation are the overproduction of nitric oxide and interleukins and the overexpression of some enzymes, including cyclooxygenase and inducible nitric oxide synthase, all of which contribute to FR production. Currently, various models in vitro and in vivo exist that permit quantification of O 2 •− and H 2 O 2 and determination of the effects of these reactive oxygen species.

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Interaction of Metal Ions with the His13-His14 Sequence Relevant to Alzheimer’s Disease

Cited by 9 publications

References 75 publications

Synthesis of Different Analogs of Ab(9-16) Peptide Mass spectrometric evidence for heavy metal binding

Synthesis of Different Analogs of Ab(9-16) Peptide Mass spectrometric evidence for heavy metal binding

Role of Metal Cations of Copper, Iron, and Aluminum and Multifunctional Ligands in Alzheimer’s Disease: Experimental and Computational Insights

Involvement of Free Radicals in the Development and Progression of Alzheimer’s Disease

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