Inhibitory effect of copper(II) on zinc(II)-induced aggregation of amyloid beta-peptide.

Article Details

Citation

Copy to clipboard

Suzuki K, Miura T, Takeuchi H

Inhibitory effect of copper(II) on zinc(II)-induced aggregation of amyloid beta-peptide.

Biochem Biophys Res Commun. 2001 Jul 27;285(4):991-6.

PubMed ID

11467850 [ View in PubMed

]

Abstract

Aggregation of amyloid beta-peptide (Abeta), a key pathological event in Alzheimer's disease, has been shown in vitro to be profoundly promoted by Zn(II). This fact suggests that some factors in the normal brain protect Abeta from the Zn(II)-induced aggregation. We demonstrate for the first time that Cu(II) effectively inhibits the Abeta aggregation by competing with Zn(II) for histidine residues. The Raman spectrum of a metal-Abeta complex in the presence of both Zn(II) and Cu(II) shows that the cross-linking of Abeta through binding of Zn(II) to the N(tau) atom of histidine is prevented by chelation of Cu(II) by the N(pi) atom of histidine and nearby amide nitrogens. The inhibitory effect is strongest at a Cu/Abeta molar ratio of around 4. Above this ratio, Cu(II) itself promotes the Abeta aggregation by binding to the phenolate oxygen of Tyr10. These results emphasize the importance of regulation of Cu(II) levels to inhibit Abeta aggregation, and are consistent with an altered metal homeostasis in Alzheimer's disease.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Copper	Amyloid beta A4 protein	Protein	Humans	Unknown	Binder	Details