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.
The bowl-shaped resorcin[4]arene-based ligand was prepared as a model of the trihistidine coordination core present in many mononuclear metalloenzymes. The -CH(2)-O-CH(2)- linkers connecting the imidazoles to the cavity allow three imidazoles to simultaneously bind a metal ion, and favor cis-coordination of two exchangeable ligands. The corresponding mononuclear Zn(II) complexes were shown to be capable of the selective guest binding and exchange at both endo and exo positions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.