Department of Neurology, The Affiliated Hospital, Guangdong Medical College, No. 2 Wenming Donglu, Xiashan District, Zhanjiang, 524023, Guangdong, People's Republic of China.
Neuromolecular Med. 2011 Dec;13(4):223-50. doi: 10.1007/s12017-011-8155-9. Epub 2011 Sep 8.
Oxidative stress has been proposed to be an important factor in the pathogenesis of Alzheimer's disease (AD) and contributed to β-amyloid (Aβ) generation. Interaction between oxidative stress and neuro-inflammation leads to Aβ generation. AD is associated with an increase in blood-brain barrier (BBB) permeability due to tight junction involvement. Oxidative stress decreases the expression of low-density lipoprotein receptor-related protein 1 and up-regulates receptor for advanced glycation end products in BBB and increases the BBB permeability, which could potentially lead to increased deposition of Aβ within AD brain. Apoptosis takes place in the pathogenesis of AD, and oxidative stress contributes to apoptosis through both extrinsic pathway and intrinsic pathway. Oxidative stress-induced apoptosis may be a potential factor to Aβ generation. Aβ generation requires two sequential cleavages of APP, with the two proteolytic enzymes: β-secretase and γ-secretase. Oxidative damage up-regulates Aβ via inducing activity of β- and γ-secretases. In this review, we will focus on the mechanism and pathway that oxidative stress contributes to Aβ generation.
氧化应激被认为是阿尔茨海默病（AD）发病机制中的一个重要因素，并导致β-淀粉样蛋白（Aβ）的产生。氧化应激与神经炎症的相互作用导致 Aβ的产生。AD 与血脑屏障（BBB）通透性的增加有关，这是由于紧密连接的参与。氧化应激降低了低密度脂蛋白受体相关蛋白 1 的表达，并上调了 BBB 中晚期糖基化终产物的受体，增加了 BBB 的通透性，这可能导致 AD 大脑中 Aβ的沉积增加。细胞凋亡发生在 AD 的发病机制中，氧化应激通过外在途径和内在途径导致细胞凋亡。氧化应激诱导的细胞凋亡可能是 Aβ产生的一个潜在因素。Aβ的产生需要 APP 的两次连续切割，两种蛋白水解酶：β-分泌酶和 γ-分泌酶。氧化损伤通过诱导β-和γ-分泌酶的活性来上调 Aβ。在这篇综述中，我们将重点讨论氧化应激促进 Aβ产生的机制和途径。
