Murakami Kazuma, Shimizu Takahiko
Commun Integr Biol. 2012 May 1;5(3):255-8. doi: 10.4161/cib.19548.
Soluble amyloid β (Aβ) oligomers cause memory loss and synaptic dysfunction in Alzheimer disease (AD). Despite intensive studies on Aβ assembly in vitro and in vivo, the localization and cellular mechanism of Aβ oligomerization are not fully understood. Previously, we demonstrated that cytoplasmic superoxide radicals contribute to drusen deposition, a hallmark of age-related macular degeneration as well as other geriatric diseases (fatty liver, skin thinning, and osteoporosis). Using a transgenic mouse model of AD, we recently clarified the role of cytoplasmic oxidative stress in cognitive impairment and oligomer formation. Moreover, we also found that these phenomena were associated with neuroinflammation, tau phosphorylation, and synaptic loss. Notably, studies using human brains support the involvement of cytoplasmic superoxide radicals in AD pathology. In this addendum to Murakami et al. (JBC 2011), we discuss and comment on intracellular Aβ oligomer formation and the possible therapeutic effects of intracellular redox state modulators.
可溶性淀粉样β（Aβ）寡聚体可导致阿尔茨海默病（AD）患者出现记忆丧失和突触功能障碍。尽管对Aβ在体外和体内的组装进行了深入研究，但Aβ寡聚化的定位和细胞机制仍未完全阐明。此前，我们证明细胞质超氧自由基会导致玻璃膜疣沉积，这是年龄相关性黄斑变性以及其他老年疾病（脂肪肝、皮肤变薄和骨质疏松症）的一个标志。利用AD转基因小鼠模型，我们最近阐明了细胞质氧化应激在认知障碍和寡聚体形成中的作用。此外，我们还发现这些现象与神经炎症、tau蛋白磷酸化和突触丧失有关。值得注意的是，使用人类大脑进行的研究支持细胞质超氧自由基参与AD病理过程。在这篇对村上等人（《生物化学杂志》，2011年）文章的补遗中，我们讨论并评论细胞内Aβ寡聚体的形成以及细胞内氧化还原状态调节剂可能的治疗作用。
