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The role of metallobiology and amyloidpeptides in Alzheimer's disease.

Abstract
The biggest risk factor for Alzheimer's disease is the process of ageing, but the mechanisms that lead to the manifestation of the disease remain to be elucidated. Why age triggers the disease is unclear but an emerging theme is the inability for a cell to efficiently maintain many key processes such as energy production, repair, and regenerative mechanisms. Metal ions are essential to the metabolic function of every cell. This review will explore the role and reported changes in metal ions in Alzheimer disease, particularly the brain, blood and cerebral spinal fluid, emphasizing how iron, copper and zinc may be involved through the interactions with amyloid precursor protein, the proteolytically cleaved peptide amyloid-beta (Aβ), and other related metalloproteins. Finally, we explore the monomeric makeup of possible Aβ dimers, what a dimeric Aβ species from Alzheimer's disease brain tissue is likely to be composed of, and discuss how metals may influence Aβ production and toxicity via a copper catalyzed dityrosine cross-link.
AuthorsBlaine R Roberts, Timothy M Ryan, Ashley I Bush, Colin L Masters, James A Duce
JournalJournal of neurochemistry (J Neurochem) Vol. 120 Suppl 1 Pg. 149-166 (Jan 2012) ISSN: 1471-4159 [Electronic] England
PMID22121980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Copyright© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.
Chemical References
  • Amyloid beta-Peptides
  • Metalloproteins
  • Copper
  • Iron
  • Zinc
Topics
  • Alzheimer Disease (blood, cerebrospinal fluid, etiology)
  • Amino Acid Sequence
  • Amyloid beta-Peptides (blood, cerebrospinal fluid, physiology)
  • Animals
  • Brain Chemistry (physiology)
  • Copper (blood, cerebrospinal fluid, physiology)
  • Humans
  • Iron (blood, cerebrospinal fluid, physiology)
  • Metalloproteins (blood, cerebrospinal fluid, physiology)
  • Molecular Sequence Data
  • Protein Binding (physiology)
  • Zinc (blood, cerebrospinal fluid, physiology)

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