Metal-Protein Attenuation With Iodochlorhydroxyquin (Clioquinol) Targeting Aβ Amyloid Deposition and Toxicity in Alzheimer Disease
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Open Access
- 1 December 2003
- journal article
- clinical trial
- Published by American Medical Association (AMA) in Archives of Neurology
- Vol. 60 (12) , 1685-1691
- https://doi.org/10.1001/archneur.60.12.1685
Abstract
ALZHEIMER DISEASE (AD) may result from the cortical accumulation of β-amyloid (Aβ). Several strategies to inhibit Aβ production and/or accumulation have been explored in experimental models of AD and are now being translated into double-blinded clinical trials.1,2 We have developed a strategy of targeting Aβ through metal-protein–attenuating compounds (MPAC), which promote the solubilization (and clearance) of Aβ and inhibit redox-active copper ion (Cu2+)–Aβ interactions that generate neurotoxic hydrogen peroxide.3,4 One such MPAC lead compound, iodochlorhydroxyquin (an anti-infective agent also known as clioquinol) induces a rapid decrease in brain Aβ deposition in a mouse model of AD.5 Clioquinol also inhibits Aβ toxicity in neuronal cell cultures, 6 possibly acting through an additional mechanism of preventing Aβ-lipid interactions.7Keywords
This publication has 3 references indexed in Scilit:
- Changes in Intracellular Calcium and Glutathione in Astrocytes as the Primary Mechanism of Amyloid NeurotoxicityJournal of Neuroscience, 2003
- Treatment of Alzheimer’s Disease with ClioquinolDementia and Geriatric Cognitive Disorders, 2001
- Changes in uptake of vitamin B12 and trace metals in brains of mice treated with clioquinolJournal of the Neurological Sciences, 2000