Amyloid-β

A chameleon walking in two worlds: A review of the trophic and toxic properties of amyloid-β

Craig S. Atwood*, Mark E. Obrenovich, Tianbing Liu, Hsien Chan, George Perry, Mark A. Smith, Ralph N. Martins

*Corresponding author for this work

Research output: Contribution to journalReview article

254 Citations (Scopus)

Abstract

Although much maligned, the amyloid-β (Aβ) protein has been shown to possess a number of trophic properties that emanate from the protein's ability to bind Cu, Fe and Zn. Aβ belongs to a group of proteins that capture redox metal ions (even under mildly acidotic conditions), thereby preventing them from participating in redox cycling with other ligands. The coordination of Cu appears to be crucial for Aβ's own antioxidant activity that has been demonstrated both in vitro as well as in the brain, cerebrospinal fluid and plasma. The chelation of Cu by Aβ would therefore be predicted to dampen oxidative stress in the mildly acidotic and oxidative environment that accompanies acute brain trauma and Alzheimer's disease (AD). Given that oxidative stress promotes Aβ generation, the formation of diffuse amyloid plaques is likely to be a compensatory response to remove reactive oxygen species. This review weighs up the evidence supporting both the trophic and toxic properties of Aβ, and while evidence for direct Aβ neurotoxicity in vivo is scarce, we postulate that the product of Aβ's antioxidant activity, hydrogen peroxide (H2O2), is likely to mediate toxicity as the levels of this oxidant rise with the accumulation of Aβ in the AD brain. We propose that metal ion chelators, antioxidants, antiinflammatories and amyloid-lowering drugs that target the reduction of H2O2 and/or Aβ generation may be efficacious in decreasing neurotoxicity. However, given the antioxidant activity of Aβ, we suggest that the excessive removal of Aβ may prevent adequate chelation of metal ions and removal of O2 -., leading to enhanced, rather than reduced, neuronal oxidative stress.

Original languageEnglish
Pages (from-to)1-16
Number of pages16
JournalBrain Research Reviews
Volume43
Issue number1
DOIs
Publication statusPublished - Sep 2003
Externally publishedYes

Keywords

  • AβPP expression
  • Acute phase response
  • Alzheimer's disease
  • Antioxidant
  • Chelation
  • Copper
  • Head trauma
  • Injury
  • Iron
  • Metal ions
  • Neurotoxic
  • Neurotrophic
  • Oxidation
  • Oxidative stress
  • Reactive oxygen species
  • Zinc

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