Nucleic acid oxidation in Alzheimer disease.
Increasing evidence suggests that oxidative stress is intimately associated with Alzheimer disease pathophysiology. Nucleic acids (nuclear DNA, mitochondrial DNA, and RNA) are one of the several cellular macromolecules damaged by reactive oxygen species, particularly the hydroxyl radical. Because neurons are irreplaceable and survive as long as the organism does, they need elaborate defense mechanisms to ensure their longevity. In Alzheimer disease, however, an accumulation of nucleic acid oxidation is observed, indicating an increased level of oxidative stress and/or a decreased capacity to repair the nucleic acid damage. In this review, we present data supporting the notion that mitochondrial and metal abnormalities are key sources of oxidative stress in Alzheimer disease. Furthermore, we outline the mechanisms of nucleic acid oxidation and repair. Finally, evidence showing the occurrence of nucleic acid oxidation in Alzheimer disease will be discussed.
Moreira
Paula I
PI
Center for Neuroscience and Cell Biology, Institute of Physiology-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Nunomura
Akihiko
A
Nakamura
Masao
M
Takeda
Atsushi
A
Shenk
Justin C
JC
Aliev
Gjumrakch
G
Smith
Mark A
MA
Perry
George
G
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D006801:Humans; D008670:Metals / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012313:RNA / Q000378:metabolism*
D008670:Metals; D012313:RNA; D004247:DNA