Department of Human Anatomy and Cell Science, University of Manitoba, Manitoba, Canada.
Department of Pharmacy, Hebei North University, Zhangjiakou 075000, Hebei Province, China.
Neural Regen Res. 2012 Feb 15;7(5):376-85. doi: 10.3969/j.issn.1673-5374.2012.05.009.
Reactive oxygen species are constantly produced in aerobic organisms as by-products of normal oxygen metabolism and include free radicals such as superoxide anion (O2 (-)) and hydroxyl radical (OH(-)), and non-radical hydrogen peroxide (H2O2). The mitochondrial respiratory chain and enzymatic reactions by various enzymes are endogenous sources of reactive oxygen species. Exogenous reactive oxygen species -inducing stressors include ionizing radiation, ultraviolet light, and divergent oxidizing chemicals. At low concentrations, reactive oxygen species serve as an important second messenger in cell signaling; however, at higher concentrations and long-term exposure, reactive oxygen species can damage cellular macromolecules such as DNA, proteins, and lipids, which leads to necrotic and apoptotic cell death. Oxidative stress is a condition of imbalance between reactive oxygen species formation and cellular antioxidant capacity due to enhanced ROS generation and/or dysfunction of the antioxidant system. Biochemical alterations in these macromolecular components can lead to various pathological conditions and human diseases, especially neurodegenerative diseases. Neurodegenerative diseases are morphologically featured by progressive cell loss in specific vulnerable neuronal cells, often associated with cytoskeletal protein aggregates forming inclusions in neurons and/or glial cells. Deposition of abnormal aggregated proteins and disruption of metal ions homeostasis are highly associated with oxidative stress. The main aim of this review is to present as much detailed information as possible that is available on various neurodegenerative disorders and their connection with oxidative stress. A variety of therapeutic strategies designed to address these pathological processes are also described. For the future therapeutic direction, one specific pathway that involves the transcription factor nuclear factor erythroid 2-related factor 2 is receiving considerable attention.
活性氧物种是有氧生物在正常氧气代谢过程中产生的副产品，包括自由基如超氧阴离子 (O2(-)) 和羟基自由基 (OH(-))，以及非自由基过氧化氢 (H2O2)。线粒体呼吸链和各种酶的酶促反应是活性氧物种的内源性来源。外源性活性氧物种诱导应激源包括电离辐射、紫外线和不同的氧化化学物质。在低浓度下，活性氧物种作为细胞信号转导中的重要第二信使；然而，在较高浓度和长期暴露下，活性氧物种会损害细胞大分子，如 DNA、蛋白质和脂质，导致坏死和凋亡性细胞死亡。氧化应激是由于 ROS 生成增强和/或抗氧化系统功能障碍导致活性氧物种形成与细胞抗氧化能力之间失衡的一种状态。这些大分子成分的生化改变可导致各种病理状况和人类疾病，特别是神经退行性疾病。神经退行性疾病的形态学特征是特定易损神经元细胞的进行性细胞丧失，通常与细胞骨架蛋白聚集体在神经元和/或神经胶质细胞中形成包含体有关。异常聚集蛋白的沉积和金属离子平衡的破坏与氧化应激高度相关。本综述的主要目的是尽可能详细地介绍各种神经退行性疾病及其与氧化应激的关系。还描述了旨在解决这些病理过程的各种治疗策略。对于未来的治疗方向，涉及转录因子核因子红细胞 2 相关因子 2 的特定途径受到了相当多的关注。
