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

doi:10.3109/10715762.2011.648188

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^* (Corresponding Author), Paula I Moreira^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

44 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 language	English
Pages (from-to)	565-576
Number of pages	12
Journal	FREE RADICAL RESEARCH
Volume	46
Issue number	4
Early online date	23 Jan 2012
DOIs	https://doi.org/10.3109/10715762.2011.648188
Publication status	Published - 2012
Externally published	Yes

Bibliographical note

Acknowledgements
The authors dedicate this article to the memory of Mark A. Smith and Lawrence M. Sayre.

Keywords

BER
8-hydroxyguanine
hydroxyl radical
mitochondria
nucleus

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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.",

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AU - Santos, Renato X

AU - Correia, Sónia C

AU - Zhu, Xiongwei

AU - Lee, Hyoung-Gon

AU - Petersen, Robert B

AU - Nunomura, Akihiko

AU - Smith, Mark A.

AU - Perry, George

AU - Moreira, Paula I

N1 - Acknowledgements The authors dedicate this article to the memory of Mark A. Smith and Lawrence M. Sayre.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - BER

KW - 8-hydroxyguanine

KW - hydroxyl radical

KW - mitochondria

KW - nucleus

U2 - 10.3109/10715762.2011.648188

DO - 10.3109/10715762.2011.648188

M3 - Review article

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EP - 576

JO - FREE RADICAL RESEARCH

JF - FREE RADICAL RESEARCH

IS - 4

ER -

Nuclear and mitochondrial DNA oxidation in Alzheimer's disease

Abstract

Bibliographical note

Keywords

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