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Copper in the brain and Alzheimer’s disease

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Abstract

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease. The brain is particularly vulnerable to oxidative damage induced by unregulated redox-active metals such as copper and iron, and the brains of AD patients display evidence of metal dyshomeostasis and increased oxidative stress. The colocalisation of copper and amyloid β (Aβ) in the glutamatergic synapse during NMDA-receptor-mediated neurotransmission provides a microenvironment favouring the abnormal interaction of redox-potent Aβ with copper under conditions of copper dysregulation thought to prevail in the AD brain, resulting in the formation of neurotoxic soluble Aβ oligomers. Interactions between Aβ oligomers and copper can further promote the aggregation of Aβ, which is the core component of extracellular amyloid plaques, a central pathological hallmark of AD. Copper dysregulation is also implicated in the hyperphosphorylation and aggregation of tau, the main component of neurofibrillary tangles, which is also a defining pathological hallmark of AD. Therefore, tight regulation of neuronal copper homeostasis is essential to the integrity of normal brain functions. Therapeutic strategies targeting interactions between Aβ, tau and metals to restore copper and metal homeostasis are discussed.

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Acknowledgments

This work was supported by funding from the Australian Research Council and the National Health and Medical Research Council (Australia) to R.A.C. and A.I.B.

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Authors and Affiliations

  1. Oxidation Biology Laboratory, The Mental Health Research Institute, 155 Oak Street, Parkville, VIC, 3052, Australia

    Ya Hui Hung, Ashley I. Bush & Robert Alan Cherny

  2. Centre for Neuroscience, The University of Melbourne, Parkville, VIC, 3010, Australia

    Ya Hui Hung

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  1. Ya Hui Hung
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Correspondence to Robert Alan Cherny.

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This article will be printed in the upcoming Journal of Biological Inorganic Chemistry special issue Cell Biology of Copper.

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Hung, Y.H., Bush, A.I. & Cherny, R.A. Copper in the brain and Alzheimer’s disease. J Biol Inorg Chem 15, 61–76 (2010). https://doi.org/10.1007/s00775-009-0600-y

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  • DOI: https://doi.org/10.1007/s00775-009-0600-y

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