Nuclear and mitochondrial DNA oxidation in Alzheimer's disease

Renato X Santos, Sónia C Correia, Xiongwei Zhu, Hyoung-Gon Lee, Robert B Petersen, Akihiko Nunomura, Mark A. Smith, George Perry, Paula I Moreira

Research output: Contribution to journalReview article

31 Citations (Scopus)

Abstract

The study of Alzheimer's disease neuropathology has been intimately associated with the field of oxidative stress for nearly 20 years. Indeed, increased markers of oxidative stress have been associated with this neurodegenerative condition, resulting from oxidation of lipids, proteins and nucleic acids. Increased nuclear and mitochondrial DNA oxidation are observed in Alzheimer's disease, stemming from increased reactive oxygen species attack to DNA bases and from the impairment of DNA repair mechanisms. Moreover, mitochondrial DNA is found to be more extensively oxidized than nuclear DNA. This review is intended to summarizes the most important cellular reactive oxygen species producers and how mitochondrial dysfunction, redox-active metals dyshomeostasis and NADPH oxidases contribute to increased oxidative stress in Alzheimer's disease. A summary of the antioxidant system malfunction will also be provided. Moreover, we will highlight the mechanisms of DNA oxidation and repair. Importantly, we will discuss evidence relating the DNA repair machinery and accumulated DNA oxidation with Alzheimer's disease.

Original languageEnglish
Pages (from-to)565-576
Number of pages12
JournalFREE RADICAL RESEARCH
Volume46
Issue number4
Early online date23 Jan 2012
DOIs
Publication statusPublished - 2012

Keywords

  • Alzheimer Disease/genetics
  • Cell Nucleus/genetics
  • DNA Damage
  • DNA, Mitochondrial/chemistry
  • Humans
  • Oxidative Stress

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