Journal article

Platinum-based inhibitors of amyloid-beta as therapeutic agents for Alzheimer's disease

Kevin J Barnham, Vijaya B Kenche, Giuseppe D Ciccotosto, David P Smith, Deborah J Tew, Xiang Liu, Keyla Perez, Greg A Cranston, Timothy J Johanssen, Irene Volitakis, Ashley I Bush, Colin L Masters, Anthony R White, Jeffrey P Smith, Robert A Cherny, Roberto Cappai

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2008

Abstract

Amelyoid-beta peptide (Abeta) is a major causative agent responsible for Alzheimer's disease (AD). Abeta contains a high affinity metal binding site that modulates peptide aggregation and toxicity. Therefore, identifying molecules targeting this site represents a valid therapeutic strategy. To test this hypothesis, a range of L-PtCl(2) (L = 1,10-phenanthroline derivatives) complexes were examined and shown to bind to Abeta, inhibit neurotoxicity and rescue Abeta-induced synaptotoxicity in mouse hippocampal slices. Coordination of the complexes to Abeta altered the chemical properties of the peptide inhibiting amyloid formation and the generation of reactive oxygen species. In comparison, the..

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