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Review
. 2018 Apr:14:450-464.
doi: 10.1016/j.redox.2017.10.014. Epub 2017 Oct 18.

Oxidative stress and the amyloid beta peptide in Alzheimer's disease

C Cheignon  1 , M Tomas  1 , D Bonnefont-Rousselot  2 , P Faller  3 , C Hureau  1 , F Collin  4
Affiliations
Review

Oxidative stress and the amyloid beta peptide in Alzheimer's disease

C Cheignon et al. Redox Biol. 2018 Apr.

Abstract

Oxidative stress is known to play an important role in the pathogenesis of a number of diseases. In particular, it is linked to the etiology of Alzheimer's disease (AD), an age-related neurodegenerative disease and the most common cause of dementia in the elderly. Histopathological hallmarks of AD are intracellular neurofibrillary tangles and extracellular formation of senile plaques composed of the amyloid-beta peptide (Aβ) in aggregated form along with metal-ions such as copper, iron or zinc. Redox active metal ions, as for example copper, can catalyze the production of Reactive Oxygen Species (ROS) when bound to the amyloid-β (Aβ). The ROS thus produced, in particular the hydroxyl radical which is the most reactive one, may contribute to oxidative damage on both the Aβ peptide itself and on surrounding molecule (proteins, lipids, …). This review highlights the existing link between oxidative stress and AD, and the consequences towards the Aβ peptide and surrounding molecules in terms of oxidative damage. In addition, the implication of metal ions in AD, their interaction with the Aβ peptide and redox properties leading to ROS production are discussed, along with both in vitro and in vivo oxidation of the Aβ peptide, at the molecular level.

Keywords: Amyloid beta peptide; Metal-ions; Oxidative damages; Oxidative stress; Reactive oxygen species.

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Figures

fx1
Graphical abstract
Fig. 1
Fig. 1
A schematic view of APP proteolytic cleavage. In the non-amyloidogenic pathway, APP is first cleaved by α-secretase and then by γ-secretase to form truncated Aβ17–40/42 peptides or by β-secretase leading to the formation of the truncated Aβ1–16. In the amyloidogenic pathway, APP is cleaved consecutively by the β- and γ-secretases leading to the formation of full-length Aβ1–40/42 peptides. According to the amyloid cascade hypothesis, the Aβ peptide would be further able to interact with metal ions present in the brain and form oligomers and then fibrils, found in the senile plaques in vivo.
Fig. 2
Fig. 2
Most frequent familial AD mutations occurring on Aβ1–43. The amino acid residues mutated and the names of the mutations are colored. (1-letter code). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.). .
Fig. 3
Fig. 3
Induced oxidative stress in cell of AD brain regions of high Aβ levels, where Aβ-metals is one of the production source for ROS. 4-HNE = 4-hydroxynonenal; 8-oxo-dG = 8-oxo-dehydroguanine. Orange star indicates oxidative damages. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).
Fig. 4
Fig. 4
Schematic representation of copper, zinc and iron coordination to Aβ. For Cu(II), only equatorial binding sites are shown.
Fig. 5
Fig. 5
(a) Mechanism of ROS production from a reductant and dioxygen catalyzed by the Cu-Aβ complex. The ROS produced are the superoxide anion (O2• −), hydrogen peroxide (H2O2) and the hydroxyl radical (HO•). (b) Top: Resting states that are the most populated states of Cu(II)-Aβ (left) and Cu(I)-Aβ (right). The redox reaction between these states is sluggish due to a high reorganization energy. Bottom: proposed Cu(I/II) environment in the catalytic in-between state .
Fig. 6
Fig. 6
Schematic view of the different oxidative modifications (red spheres), cleavages (orange arrows) and interactions (dashed arrows) undergone by the Aβ1–42 peptide during the copper-mediated oxidation. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).
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References

    1. Sousa F.L., Thiergart T., Landan G., Nelson-Sathi S., Pereira I.A.C., Allen J.F., Lane N., Martin W.F. Early bioenergetic evolution. Philos. Trans. R. Soc. B: Biol. Sci. 2013;368(1622) - PMC - PubMed
    1. Gorrini C., Harris I.S., Mak T.W. Modulation of oxidative stress as an anticancer strategy. Nat. Rev. Drug Discov. 2013;12(12):931–947. - PubMed
    1. Halliwell B., Gutteridge J.M.C. Clarendon Press; Oxford: 1989. Free Radicals in Biology and Medicine.
    1. Chassaing S., Collin F., Dorlet P., Gout J., Hureau C., Faller P. Copper and heme-mediated abeta toxicity: redox chemistry, abeta oxidations and anti-ROS compounds. Curr. Top. Med. Chem. 2012;12(22):2573–2595. - PubMed
    1. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J. Neurochem. 2006;97(6):1634–1658. - PubMed

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