Metodiewa D, Kośka C
Institute of Applied Radiation Chemistry, Technical University of Łódz, Poland.
Neurotox Res. 2000 Feb;1(3):197-233. doi: 10.1007/BF03033290.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed under physiological conditions in the human body and are removed by cellular antioxidant defense system. During oxidative stress their increased formation leads to tissue damage and cell death. This process may be especially important in the central nervous system (CNS) which is vulnerable to ROS and RNS damage as the result of the brain high O(2) consumption, high lipid content and the relatively low antioxidant defenses in brain, compared with other tissues. Recently there has been an increased number of reports suggesting the involvement of free radicals and their non-radical derivatives in a variety of pathological events and multistage disorders including neurotoxicity, apoptotic death of neurons and neural disorders: Alzheimer's (AD), Parkinson's disease (PD) and schizophrenia. Taking into consideration the basic molecular chemistry of ROS and RNS, their overall generation and location, in order to control or suppress their action it is essential to understand the fundamental aspects of this problem. In this presentation we review and summarize the basics of all the recently known and important properties, mechanisms, molecular targets, possible involvement in cellular (neural) degeneration and apoptotic death and in pathogenesis of AD, PD and schizophrenia. The aim of this article is to provide an overview of our current knowledge of this problem and to inspire experimental strategies for the evaluation of optimum innovative therapeutic trials. Another purpose of this work is to shed some light on one of the most exciting recent advances in our understanding of the CNS: the realisation that RNS pathway is highly relevant to normal brain metabolism and to neurologic disorders as well. The interactions of RNS and ROS, their interconversions and the ratio of RNS/ROS could be an important neural tissue injury mechanism(s) involved into etiology and pathogenesis of AD, PD and schizophrenia. It might be possible to direct therapeutic efforts at oxidative events in the pathway of neuron degeneration and apoptotic death. From reviewed data, no single substance can be recommended for use in human studies. Some of the recent therapeutic strategies and neuroprotective trials need further development particularly those of antioxidants enhancement. Such an approach should also consider using combinations of radical(s) scavengers rather than a single substance.
活性氧（ROS）和活性氮（RNS）在人体生理条件下形成，并由细胞抗氧化防御系统清除。在氧化应激期间，它们生成的增加会导致组织损伤和细胞死亡。这一过程在中枢神经系统（CNS）中可能尤为重要，由于大脑耗氧量高、脂质含量高以及与其他组织相比大脑中抗氧化防御相对较低，中枢神经系统易受ROS和RNS损伤。最近，越来越多的报告表明自由基及其非自由基衍生物参与了多种病理事件和多阶段疾病，包括神经毒性、神经元凋亡死亡和神经疾病：阿尔茨海默病（AD）、帕金森病（PD）和精神分裂症。考虑到ROS和RNS的基本分子化学、它们的总体生成和位置，为了控制或抑制它们的作用，了解这个问题的基本方面至关重要。在本报告中，我们回顾并总结了所有最近已知的重要特性、机制、分子靶点、可能参与细胞（神经）变性和凋亡死亡以及AD、PD和精神分裂症发病机制的基础知识。本文的目的是概述我们目前对这个问题的认识，并激发评估最佳创新治疗试验的实验策略。这项工作的另一个目的是阐明我们对中枢神经系统理解中最令人兴奋的最新进展之一：认识到RNS途径与正常脑代谢以及神经疾病也高度相关。RNS和ROS的相互作用、它们的相互转化以及RNS/ROS的比例可能是参与AD、PD和精神分裂症病因和发病机制的重要神经组织损伤机制。有可能将治疗努力指向神经元变性和凋亡死亡途径中的氧化事件。从综述的数据来看，没有单一物质可推荐用于人体研究。一些最近的治疗策略和神经保护试验需要进一步发展，特别是那些增强抗氧化剂的试验。这种方法还应考虑使用自由基清除剂的组合而不是单一物质。
