The neurotoxicity of glutamate, dopamine, iron and reactive oxygen species: functional interrelationships in health and disease: a review-discussion.

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.