Title: Metal-Protein Attenuating Compounds (MPACs) for the Treatment of Alzheimers Disease
Volume: 1
Issue: 1
Author(s): Kevin J. Barnham, Robert A. Cherny, Roberto Cappai, Simon Melov, Colin L. Masters and Ashley I. Bush
Affiliation:
Abstract: Aberrant metal protein interactions leading to the generation of toxic reactive oxygen species and protein denaturation have been implicated in a number of neurodegenerative diseases. A breakdown in metal homeostasis plays a critical role in these disorders including Alzheimers disease (AD), where abnormal interactions of copper and zinc ions with ß-amyloid (Aß) may underlie the pathogenesis. We have developed metal-protein attenuating compounds (MPACs) as a novel class of therapeutic agent that target pathogenic interactions of metals with proteins. The prototype for this class of compound is clioquinol (CQ), a small hydrophobic molecule capable of crossing the blood brain barrier. This compound has been shown to have beneficial effects in both a transgenic mouse model of AD and a recently completed small-scale phase II clinical trial.
