Aliev Gjumrakch, Li Yi, Palacios Hector H, Obrenovich Mark E
School of Health Science and Healthcare Administration, University of Atlanta, Atlanta, Georgia 30360, USA.
Recent Pat Cardiovasc Drug Discov. 2011 Sep;6(3):222-41. doi: 10.2174/157489011797376942.
Oxidative stress in the cardiovascular system, including brain microvessels and/or parenchymal cells results in an accumulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) compounds thus promoting leukocyte adhesion and increasing endothelial permeability. The resulting chronic injury stimulus results in progressive cellular hypometabolism. We propose that hypometabolism, coupled with oxidative stressors, is responsible for most Alzheimer disease (AD) and cerebrovascular accidents (CVAs) and appears to be a central initiating factor for vascular abnormalities, mitochondrial damage and an imbalance in the activity of vasoactive substances, such as different isoforms of nitric oxide synthase (NOS), endothelin-1 (ET-1), oxidative stress markers, mtDNA and mitochondrial enzymes in the vascular wall and in brain parenchymal cells. At higher concentrations, ROS induces cell injury and death, which occurs during the aging process, where accelerated generation of ROS and a gradual decline in cellular antioxidant defense mechanisms, especially in the mitochondria. Vascular endothelial and neuronal mitochondria are especially vulnerable to oxidative stress due to their role in energy supply and use, which can cause a cascade of debilitating factors such as the production of giant and/or vulnerable young mitochondrion who's DNA has been compromised. Therefore, mitochondrial DNA abnormalities such as overproliferation and or deletion can be used as a key marker for diseases differentiation and effectiveness of the treatment. We speculate that specific antioxidants such as acetyl-L-carnitine and R-alpha lipoic acid seem to be potential treatments for AD. They target the factors that damage mitochondria and reverse its effect, thus eliminating the imbalance seen in energy production and restore the normal cellular function, making these antioxidants very powerful alternate strategies for the treatment of cardiovascular cerebrovascular as well as neurodegenerative diseases including AD. Future potential exploration using mtDNA markers can be considered more accurate hallmarks for diagnosis and monitoring treatment of human diseases. The present article discusses some of the patents regarding the oxidative stress.
心血管系统中的氧化应激，包括脑微血管和/或实质细胞，会导致活性氧（ROS）和活性氮（RNS）化合物的积累，从而促进白细胞粘附并增加内皮通透性。由此产生的慢性损伤刺激会导致进行性细胞代谢减退。我们认为，代谢减退与氧化应激源共同作用，是大多数阿尔茨海默病（AD）和脑血管意外（CVA）的原因，并且似乎是血管异常、线粒体损伤以及血管活性物质（如不同亚型的一氧化氮合酶（NOS）、内皮素-1（ET-1））活性失衡、氧化应激标志物、mtDNA以及血管壁和脑实质细胞中线粒体酶失衡的核心起始因素。在较高浓度下，ROS会诱导细胞损伤和死亡，这发生在衰老过程中，此时ROS生成加速，细胞抗氧化防御机制逐渐下降，尤其是在线粒体中。血管内皮和神经元线粒体由于其在能量供应和利用中的作用，特别容易受到氧化应激的影响，这可能会导致一系列使人衰弱的因素，如产生巨大和/或脆弱的年轻线粒体，其DNA已受损。因此，线粒体DNA异常，如过度增殖和/或缺失，可作为疾病鉴别和治疗效果的关键标志物。我们推测，特定的抗氧化剂，如乙酰-L-肉碱和R-α硫辛酸，似乎是AD的潜在治疗方法。它们针对损害线粒体的因素并逆转其作用，从而消除能量产生中出现的失衡并恢复正常细胞功能，使这些抗氧化剂成为治疗心血管、脑血管以及包括AD在内的神经退行性疾病的非常有效的替代策略。未来使用mtDNA标志物的潜在探索可被视为人类疾病诊断和监测治疗的更准确标志。本文讨论了一些关于氧化应激的专利。
