Metal-Protein Attenuating Compounds (MPACs) for the Treatment of Alzheimers Disease

Author(s): Kevin J. Barnham , Robert A. Cherny , Roberto Cappai , Simon Melov , Colin L. Masters , Ashley I. Bush .

Journal Name: Drug Design Reviews - Online (Discontinued)

Volume 1 , Issue 1 , 2004

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.

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Article Details

VOLUME: 1
ISSUE: 1
Year: 2004
Page: [75 - 82]
Pages: 8
DOI: 10.2174/1567269043480690

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