Murakami Kazuma, Shimizu Takahiko, Irie Kazuhiro
Laboratory of Organic Chemistry in Life Science, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
J Amino Acids. 2011;2011:654207. doi: 10.4061/2011/654207. Epub 2011 Jan 16.
Oxidative stress is closely involved in age-related diseases and ageing itself. There is evidence of the leading contribution of oxidative damage to neurodegenerative disease, in contrast to other diseases where oxidative stress plays a secondary role. The 42-mer amyloid β (Aβ42) peptide is thought to be a culprit in the pathogenesis of Alzheimer's disease (AD). Aβ42 aggregates form the oligomeric assembly and show neurotoxicity, causing synaptic dysfunction. Aβ42 also induces tissue oxidation (DNA/RNA, proteins, and lipids) through trace metals (Cu, Zn, and Fe), which can be protected by antioxidant enzymes, vitamin C, and vitamin E. Superoxide dismutase catalyzes the conversion of toxic superoxide radical to less reactive hydrogen peroxide, contributing to protection from AD. Here we review the involvement of oxidative stress in AD progression induced from an imbalance between the radical formation of Aβ42 itself together with unique turn structure at positions Glu22 and Asp23 and several defense systems.
氧化应激与年龄相关疾病及衰老过程密切相关。有证据表明，氧化损伤在神经退行性疾病中起主要作用，而在其他疾病中氧化应激则起次要作用。42个氨基酸的淀粉样β蛋白（Aβ42）肽被认为是阿尔茨海默病（AD）发病机制中的罪魁祸首。Aβ42聚集体形成寡聚体组装体并表现出神经毒性，导致突触功能障碍。Aβ42还通过痕量金属（铜、锌和铁）诱导组织氧化（DNA/RNA、蛋白质和脂质），而抗氧化酶、维生素C和维生素E可以起到保护作用。超氧化物歧化酶催化将有毒的超氧自由基转化为活性较低的过氧化氢，有助于预防AD。在此，我们综述了氧化应激在由Aβ42自身的自由基形成与Glu22和Asp23位点独特的转角结构之间的失衡以及几种防御系统所诱导的AD进展中的作用。
