Fatokun Amos Akintayo, Stone Trevor William, Smith Robert Anthony
Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Front Biosci. 2008 May 1;13:3288-311. doi: 10.2741/2926.
Substantial pieces of direct and indirect evidence have mounted over the years linking the induction of oxidative stress to a plethora of disease conditions, not least those associated with the death of neurons. The causal relationship between oxidative damage and neurodegeneration is, however, not yet clear and still a subject of intense investigation. Nevertheless, the phenomenon of oxidative neuronal death has received considerable attention in a frantic search for efficacious therapies for the management of neurological and neurodegenerative conditions. The redox-active nature of reactive oxygen species (ROS), which in their excessive levels induce oxidative stress, the prevalence of ROS production in biological systems, the complexity of interrelationships among these species, and the context-dependent adequacy and resilience of the antioxidant defense systems are some of the challenges that basic research has to grapple with to advance successfully to the translational stage. Much still has to be understood for research efforts in this field to yield enduring therapies. In this review, we examine the nature (chemistry) of ROS, the relationships between them, their physiological functions, the roles of oxidative stress in neurodegeneration, the mechanisms of cell death induced by oxidant species, and the available means of protecting neurons against oxidative damage.
多年来,大量直接和间接证据不断涌现,将氧化应激的诱导与众多疾病状况联系起来,尤其是那些与神经元死亡相关的疾病。然而,氧化损伤与神经退行性变之间的因果关系尚不清楚,仍是深入研究的课题。尽管如此,在疯狂寻找有效治疗方法以管理神经和神经退行性疾病的过程中,氧化性神经元死亡现象受到了相当多的关注。活性氧(ROS)的氧化还原活性本质(过量时会诱导氧化应激)、生物系统中ROS产生的普遍性、这些物质之间相互关系的复杂性以及抗氧化防御系统的背景依赖性充分性和弹性,是基础研究为成功推进到转化阶段必须应对的一些挑战。为了使该领域的研究努力产生持久的治疗方法,仍有许多需要了解的地方。在这篇综述中,我们研究了ROS的性质(化学)、它们之间的关系、它们的生理功能、氧化应激在神经退行性变中的作用、氧化物种诱导细胞死亡的机制以及保护神经元免受氧化损伤的现有方法。