Veurink G, Fuller S J, Atwood C S, Martins R N
The Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Australia.
Ann Hum Biol. 2003 Nov-Dec;30(6):639-67. doi: 10.1080/03014460310001620144.
This paper reviews a wide range of recent studies that have linked AD-associated biochemical and physiological changes with oxidative stress and damage. Some of these changes include disruptions in metal ion homeostasis, mitochondrial damage, reduced glucose metabolism, decreased intracellular pH and inflammation. Although the changes mentioned above are associated with oxidative stress, in most cases, a cause and effect relationship is not clearcut, as many changes are interlinked. Increases in the levels of Abeta peptides, the main protein components of the cerebral amyloid deposits of AD, have been demonstrated to occur in inherited early-onset forms of AD, and as a result of certain environmental and genetic risk factors. Abeta peptides have been shown to exhibit superoxide dismutase activity, producing hydrogen peroxide which may be responsible for the neurotoxicity exhibited by this peptide in vitro. This review also discusses the biochemical aspects of oxidative stress, antioxidant defence mechanisms, and possible antioxidant therapeutic measures which may be effective in counteracting increased levels of oxidative stress. In conclusion, this review provides support for the theory that damage caused by free radicals and oxidative stress is a primary cause of the neurodegeneration seen in AD with Abeta postulated as an initiator of this process.
本文综述了一系列近期的研究，这些研究将与阿尔茨海默病（AD）相关的生化和生理变化与氧化应激及损伤联系起来。其中一些变化包括金属离子稳态的破坏、线粒体损伤、葡萄糖代谢降低、细胞内pH值下降以及炎症。尽管上述变化与氧化应激有关，但在大多数情况下，因果关系并不明确，因为许多变化相互关联。已证明，在遗传性早发性AD以及某些环境和遗传风险因素导致的AD中，β淀粉样肽（Aβ肽）水平会升高，Aβ肽是AD脑淀粉样沉积物的主要蛋白质成分。研究表明，Aβ肽具有超氧化物歧化酶活性，可产生过氧化氢，这可能是该肽在体外表现出神经毒性的原因。本综述还讨论了氧化应激的生化方面、抗氧化防御机制以及可能有效对抗氧化应激水平升高的抗氧化治疗措施。总之，本综述支持以下理论：自由基和氧化应激造成的损伤是AD中神经退行性变的主要原因，Aβ肽被假定为这一过程的启动因素。
