Redox-active iron mediates amyloid-β toxicity

Catherine Rottkamp, Arun K. Raina, Xiongwei Zhu, Elizabeth Gaier, Ashley I. Bush, Craig S. Atwood, Mordechai Chevion, George Perry, Mark A. Smith

Research output: Contribution to journalArticle

320 Citations (Scopus)

Abstract

While amyloid-β toxicity is mediated by oxidative stress and can be attenuated by antioxidants, the actual biochemical mechanism underlying neurotoxicity remains to be established. However, since aggregated amyloid-β can interact with transition metals, such as iron, both in vitro and in vivo, we suspected that bound iron might be the mediator of toxicity such that holo- and apo-amyloid would have differential effects on cellular viability. Here we demonstrate that when amyloid-β is pretreated with the iron chelator deferoxamine, neuronal toxicity is significantly attenuated while conversely, incubation of holo-amyloid-β with excess free iron restores toxicity to original levels. These data, taken together with the known sequelae of amyloid-β, suggest that the toxicity of amyloid-β is mediated, at least in part, via redox-active iron that precipitates lipid peroxidation and cellular oxidative stress.

Original languageEnglish (US)
Pages (from-to)447-450
Number of pages4
JournalFree Radical Biology and Medicine
Volume30
Issue number4
DOIs
StatePublished - Feb 15 2001
Externally publishedYes

Fingerprint

Amyloid
Oxidation-Reduction
Toxicity
Iron
Oxidative stress
Oxidative Stress
Deferoxamine
Chelating Agents
Lipid Peroxidation
Transition metals
Precipitates
Antioxidants
Metals
Lipids

Keywords

  • Alzheimer disease
  • Amyloid-β
  • Free radicals
  • Iron
  • Neurotoxicity
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Rottkamp, C., Raina, A. K., Zhu, X., Gaier, E., Bush, A. I., Atwood, C. S., ... Smith, M. A. (2001). Redox-active iron mediates amyloid-β toxicity. Free Radical Biology and Medicine, 30(4), 447-450. https://doi.org/10.1016/S0891-5849(00)00494-9

Redox-active iron mediates amyloid-β toxicity. / Rottkamp, Catherine; Raina, Arun K.; Zhu, Xiongwei; Gaier, Elizabeth; Bush, Ashley I.; Atwood, Craig S.; Chevion, Mordechai; Perry, George; Smith, Mark A.

In: Free Radical Biology and Medicine, Vol. 30, No. 4, 15.02.2001, p. 447-450.

Research output: Contribution to journalArticle

Rottkamp, C, Raina, AK, Zhu, X, Gaier, E, Bush, AI, Atwood, CS, Chevion, M, Perry, G & Smith, MA 2001, 'Redox-active iron mediates amyloid-β toxicity', Free Radical Biology and Medicine, vol. 30, no. 4, pp. 447-450. https://doi.org/10.1016/S0891-5849(00)00494-9
Rottkamp, Catherine ; Raina, Arun K. ; Zhu, Xiongwei ; Gaier, Elizabeth ; Bush, Ashley I. ; Atwood, Craig S. ; Chevion, Mordechai ; Perry, George ; Smith, Mark A. / Redox-active iron mediates amyloid-β toxicity. In: Free Radical Biology and Medicine. 2001 ; Vol. 30, No. 4. pp. 447-450.
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