title: Nuclear and mitochondrial DNA oxidation in Alzheimer's disease.
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.
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Renato X
authors.initials: RX
authors.lastname: Santos
authors.forename: Sónia C
authors.initials: SC
authors.lastname: Correia
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: Hyoung-Gon
authors.initials: HG
authors.lastname: Lee
authors.forename: Robert B
authors.initials: RB
authors.lastname: Petersen
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nunomura
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics*; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D018384:Oxidative Stress
chemical_list: D004272:DNA, Mitochondrial