Neuromolecular Med 2011 Dec;13 (4): 223-50. [IF:4.657]
Oxidative Stress and β-Amyloid Protein in Alzheimer's Disease.
Cai Z , Zhao B , Ratka A .
Department of Neurology, The Affiliated Hospital, Guangdong Medical College, No. 2 Wenming Donglu, Xiashan District, Zhanjiang, 524023, Guangdong, People's Republic of China.
广东医学院附属医院神经内科
Abstract
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.
摘要:
氧化应激被提出是阿尔茨海默病(AD)发病机理的一个重要因素，有助于β-淀粉样蛋(Aβ)白的生成。氧化应激和神经炎症的相互作用导致Aβ的生成。由于联系紧密，AD与血脑屏障（BBB）的渗透性增加有关。氧化应激降低低密度脂蛋白受体相关性蛋白1，并上调高度糖化终产物在BBB上的受体，因此增加了BBB的通透性，最终使得AD患者大脑中Aβ的沉积增加。细胞凋亡是AD的一个发病机理，而氧化应激通过外部和内部条件促进细胞凋亡发生，因而由氧化应激诱发的细胞凋亡可能是Aβ生成的一个潜在因素。Aβ的生成要求两序列裂解反应，两种蛋白水解酶：β分泌酶和γ分泌酶。氧化通过调节β分泌酶和γ分泌酶的活性来上调Aβ。在这篇报告中，我们将集中研究氧化应激对Aβ生成的机制和途径。
