Signal transduction cascades associated with oxidative stress in Alzheimer's disease

Robert B. Petersen, Akihiko Nunomura, Hyoung Gon Lee, Gemma Casadesus, George Perry, Mark A. Smith, Xiongwei Zhu

Research output: Contribution to journalReview articlepeer-review

84 Scopus citations

Abstract

It has now been established through multiple lines of evidence that oxidative stress is an early event in Alzheimer's disease, occurring prior to the canonical cytopathology. Thus, oxidative stress likely plays a key pathogenic role in the disease and is clearly involved in the cell loss and other neuropathology associated with Alzheimer's disease as demonstrated by the large number of metabolic signs of oxidative stress and by markers of oxidative damage. One puzzling observation, however, is that oxidative damage decreases with disease progression, such that levels of markers of rapidly formed oxidative damage, which are initially elevated, decrease as the disease progresses to advanced Alzheimer's disease. This finding indicates that reactive oxygen species not only cause damage to cellular structures but also provoke cellular responses, such as the compensatory upregulation of antioxidant enzymes found in vulnerable neurons in Alzheimer's disease. Not surprisingly, stress-activated protein kinase pathways, which are activated by oxidative stress, are extensively activated during Alzheimer's disease. In this review, we present the evidence of oxidative stress and compensatory responses that occur in Alzheimer's disease with a particular focus on the roles and mechanism of activation of stress-activated protein kinase pathways.

Original languageEnglish
Pages (from-to)143-152
Number of pages10
JournalJournal of Alzheimer's Disease
Volume11
Issue number2
DOIs
StatePublished - 2007

Keywords

  • Alzheimer's disease
  • Heme oxygenase
  • Mitochondria
  • Oxidative stress
  • Stress-activated protein kinase
  • Transition metals

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