title: Copper and heme-mediated Abeta toxicity: redox chemistry, Abeta oxidations and anti-ROS compounds.
abstract: Oxidative stress mediated by reactive oxygen or nitrogen species (ROS/RNS) seems to be implicated in several diseases including neurodegenerative ones. In one of them, namely Alzheimer's disease, there is a large body of evidence that the aggregation of the peptide amyloid-beta (Abeta) is implicated in the generation of the oxidative stress. 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 Alzheimer's disease, it is thought that metals (mostly Cu, Fe and heme) can bind to amyloid-beta and that such systems are involved in the generation of oxidative stress. In the present article, we review the role of ROS/RNS produced by redox active Cu ions and heme compounds in the context of the amyloid cascade. We focus on (i) the coordination chemistry of Cu and heme to Abeta; (ii) the role of the corresponding Abeta adducts in the (catalytic) production of ROS/RNS; (iii) the subsequent degradation of Abeta by these reactive species and (iv) the use of antioxidants, in particular metal sequestering compounds and direct antioxidants like polyphenols as a therapeutic strategies.
authors: LSPCMIB (Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique), Université de Toulouse, UMR-CNRS 5068, 118 route de Narbonne, F-31062 Toulouse Cedex 9, France.
authors: Stefan
authors: S
authors: Chassaing
authors: Fabrice
authors: F
authors: Collin
authors: Pierre
authors: P
authors: Dorlet
authors: Jérôme
authors: J
authors: Gout
authors: Christelle
authors: C
authors: Hureau
authors: Peter
authors: P
authors: Faller
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011073:Polyamines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D011073:Polyamines; D017382:Reactive Oxygen Species; D006418:Heme; D003300:Copper