Mecocci P, MacGarvey U, Beal M F
Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114.
Ann Neurol. 1994 Nov;36(5):747-51. doi: 10.1002/ana.410360510.
Oxidative damage to DNA may play a role in both normal aging and in neurodegenerative diseases. We examined whether Alzheimer's disease (AD) is associated with increased oxidative damage to nDNA and mtDNA in postmortem brain tissue. We measured the oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (OH8dG), in DNA isolated from three regions of cerebral cortex and cerebellum in 13 AD and 13 age-matched controls. There was a significant threefold increase in the amount of OH8dG in mtDNA in parietal cortex of AD patients compared with controls. In the entire group of samples there was a small significant increase in oxidative damage to nDNA and a highly significant threefold increase in oxidative damage to mtDNA in AD compared with age-matched controls. These results confirm that mitochondrial DNA is particularly sensitive to oxidative damage, and they show that there is increased oxidative damage to DNA in AD, which may contribute to the neurodegenerative process.
DNA的氧化损伤可能在正常衰老和神经退行性疾病中都起作用。我们研究了阿尔茨海默病（AD）是否与死后脑组织中核DNA（nDNA）和线粒体DNA（mtDNA）的氧化损伤增加有关。我们测量了从13例AD患者和13例年龄匹配的对照者的大脑皮质和小脑三个区域分离的DNA中的氧化核苷8-羟基-2'-脱氧鸟苷（OH8dG）。与对照组相比，AD患者顶叶皮质mtDNA中OH8dG的量显著增加了三倍。在整个样本组中，与年龄匹配的对照组相比，AD患者的nDNA氧化损伤有小幅显著增加，mtDNA氧化损伤有高度显著的三倍增加。这些结果证实线粒体DNA对氧化损伤特别敏感，并且表明AD患者的DNA氧化损伤增加，这可能导致神经退行性过程。
