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HERO ID
3701940
Reference Type
Journal Article
Subtype
Review
Title
Metal dyshomeostasis and oxidative stress in Alzheimer's disease
Author(s)
Greenough, MA; Camakaris, J; Bush, AI
Year
2013
Is Peer Reviewed?
1
Journal
Neurochemistry International
ISSN:
0197-0186
EISSN:
1872-9754
Volume
62
Issue
5
Page Numbers
540-555
Language
English
PMID
22982299
DOI
10.1016/j.neuint.2012.08.014
Web of Science Id
WOS:000317873900004
Abstract
Alzheimer's disease is the leading cause of dementia in the elderly and is defined by two pathological hallmarks; the accumulation of aggregated amyloid beta and excessively phosphorylated Tau proteins. The etiology of Alzheimer's disease progression is still debated, however, increased oxidative stress is an early and sustained event that underlies much of the neurotoxicity and consequent neuronal loss. Amyloid beta is a metal binding protein and copper, zinc and iron promote amyloid beta oligomer formation. Additionally, copper and iron are redox active and can generate reactive oxygen species via Fenton (and Fenton-like chemistry) and the Haber-Weiss reaction. Copper, zinc and iron are naturally abundant in the brain but Alzheimer's disease brain contains elevated concentrations of these metals in areas of amyloid plaque pathology. Amyloid beta can become pro-oxidant and when complexed to copper or iron it can generate hydrogen peroxide. Accumulating evidence suggests that copper, zinc, and iron homeostasis may become perturbed in Alzheimer's disease and could underlie an increased oxidative stress burden. In this review we discuss oxidative/nitrosative stress in Alzheimer's disease with a focus on the role that metals play in this process. Recent studies have started to elucidate molecular links with oxidative/nitrosative stress and Alzheimer's disease. Finally, we discuss metal binding compounds that are designed to cross the blood brain barrier and restore metal homeostasis as potential Alzheimer's disease therapeutics.
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