Formation of the 42-mer Amyloid β Radical and the Therapeutic Role of Superoxide Dismutase in Alzheimer's Disease.
Formation of the 42-mer Amyloid β Radical and the Therapeutic Role of Superoxide Dismutase in Alzheimer's Disease.
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DOI：
10.4061/2011/654207
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Irie K
中科院分区：
文献类型：
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作者：
Murakami K;Shimizu T;Irie K
氧化应激与年龄相关疾病和衰老本身密切相关。有证据表明，与氧化应激起次要作用的其他疾病相比，氧化损伤对神经退行性疾病起主要作用。42-mer淀粉样β（Aβ42）肽被认为是阿尔茨海默病（AD）发病机制的罪魁祸首。Aβ42聚集体形成寡聚体组装并显示神经毒性，引起突触功能障碍。Aβ42还通过微量金属（Cu、Zn和Fe）诱导组织氧化（DNA/RNA、蛋白质和脂质），抗氧化酶、维生素C和维生素E可保护这些金属。超氧化物歧化酶催化有毒的超氧化物自由基转化为反应性较低的过氧化氢，有助于预防AD。本文综述了氧化应激在AD进展中的作用，氧化应激是由Aβ42自身的自由基形成以及Glu 22和Asp 23位置独特的转角结构和几种防御系统之间的不平衡引起的。
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.