Smythies J
Center for Brain and Cognition, Department of Psychology, UCSD, La Jolla, CA 92093-0109, USA.
Neurotox Res. 1999 Sep;1(1):27-39. doi: 10.1007/BF03033337.
The fact that glutamate, dopamine, iron and reactive oxygen species are potentially individually highly neurotoxic molecules is well known. The purpose of this review is to examine the less well known complex ways in which their normal biological, as well as their neurotoxic activity, are interconnected in relation to fundamental neuronal functions. These functions include synaptic plasticity (formation and removal of synapses), endocytosis-based recycling of receptors for neurotransmitters and neuromodulators, the role of the redox balance between reactive oxygen species and antioxidants in synaptic function, and the possible role of iron-catecholamine complexes in antioxidant protection and intraneuronal iron transport. These systems are closely involved in several diseases of the nervous system including Parkinson's disease, schizophrenia and Alzheimer's disease. In all these oxidative stress and a failure of antioxidant defenses are involved. In the former two the neurotoxicity of catecholaminergic o-quinones is important. In the later excessive oxidation of neuronal membranes and excessive endocytosis and receptor recycling may be an important factor.
谷氨酸、多巴胺、铁和活性氧物种可能各自都是具有高度神经毒性的分子，这一事实众所周知。本综述的目的是研究一些不太为人所知的复杂方式，即它们的正常生物学功能以及神经毒性活性与基本神经元功能之间是如何相互关联的。这些功能包括突触可塑性（突触的形成和消除）、基于内吞作用的神经递质和神经调质受体循环利用、活性氧物种与抗氧化剂之间的氧化还原平衡在突触功能中的作用，以及铁 - 儿茶酚胺复合物在抗氧化保护和神经元内铁转运中的可能作用。这些系统与包括帕金森病、精神分裂症和阿尔茨海默病在内的几种神经系统疾病密切相关。在所有这些疾病中，都涉及氧化应激和抗氧化防御功能的失效。在前两种疾病中，儿茶酚胺能邻醌的神经毒性很重要。在后者中，神经元膜的过度氧化以及过度的内吞作用和受体循环利用可能是一个重要因素。
