Mitochondrial- and endoplasmic reticulum-associated oxidative stress in Alzheimer's disease: from pathogenesis to biomarkers.
Mitochondrial- and endoplasmic reticulum-associated oxidative stress in Alzheimer's disease: from pathogenesis to biomarkers.
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DOI：
10.1155/2012/735206
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发表时间：
2012
影响因子：
--
通讯作者：
Oliveira CR
中科院分区：
文献类型：
--
作者：
Ferreiro E;Baldeiras I;Ferreira IL;Costa RO;Rego AC;Pereira CF;Oliveira CR
阿尔茨海默病（AD）是老年痴呆症的最常见原因，影响全世界数百万人。AD脑中的病理变化包括淀粉样蛋白斑块的存在、神经元缠结、神经元和突触的损失以及氧化损伤。这些变化与线粒体功能障碍和内质网（ER）应激密切相关。线粒体功能障碍与活性氧（ROS）的产生和神经元驱动的细胞凋亡密切相关，这些在AD患者的脑中似乎加重。同时，线粒体与ER密切相关，两种细胞器之间的有害串扰已被证明参与AD中的神经元变性。增强正常和/或折叠缺陷蛋白质表达的刺激激活适应性未折叠蛋白质反应（UPR），如果未解决，可导致凋亡性细胞死亡。ER应激还诱导ROS的产生，其与线粒体ROS和几种抗氧化剂防御的活性降低一起促进慢性氧化应激。在本文中，我们讨论了在AD细胞和动物模型中，以及在AD患者的生物体液中，线粒体和ER功能障碍在氧化损伤中的关键作用。发展与氧化应激相关的外周和脑脊液生物标志物的进展也将进行总结。
Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting several million of people worldwide. Pathological changes in the AD brain include the presence of amyloid plaques, neurofibrillary tangles, loss of neurons and synapses, and oxidative damage. These changes strongly associate with mitochondrial dysfunction and stress of the endoplasmic reticulum (ER). Mitochondrial dysfunction is intimately linked to the production of reactive oxygen species (ROS) and mitochondrial-driven apoptosis, which appear to be aggravated in the brain of AD patients. Concomitantly, mitochondria are closely associated with ER, and the deleterious crosstalk between both organelles has been shown to be involved in neuronal degeneration in AD. Stimuli that enhance expression of normal and/or folding-defective proteins activate an adaptive unfolded protein response (UPR) that, if unresolved, can cause apoptotic cell death. ER stress also induces the generation of ROS that, together with mitochondrial ROS and decreased activity of several antioxidant defenses, promotes chronic oxidative stress. In this paper we discuss the critical role of mitochondrial and ER dysfunction in oxidative injury in AD cellular and animal models, as well as in biological fluids from AD patients. Progress in developing peripheral and cerebrospinal fluid biomarkers related to oxidative stress will also be summarized.