Metal Ions in Neuroscience

C I Ragan

doi:10.1155/mbd.1997.125

Abstract

Metal ions are believed to participate in many neurodegenerative conditions. In excitotoxic cell death there is convincing evidence for the participation of Ca2+ and Zn2+ ions although the exact molecular mechanisms by which these metals exert their effects are unclear. Only in one instance has the metal binding site of metalloenzymes been exploited for therapeutic purposes and this is the use of Li+ in the treatment of bipolar affective disorder. Again the exact molecular target is not clear but is likely to involve a Mg2+-dependent enzyme of an intracellular signalling pathway. In Parkinson's disease, the selective loss of dopaminergic neurones in the substantia nigra may be caused by radical-mediated damage and there is good evidence to suggest that Fe2+ or 3+ is important in promoting formation of radical species. The evidence that free radicals are important in mediating other neurodegenerative conditions is less strong but still substantial enough to suggest that removal of reactive oxygen species or preventing their formation may be a valid approach to therapy.

Highlights

In this article, rather than describe the role of metal ions in normal neuronal function, have focused on abnormal neuronal conditions and the role of metal ions in causing or in preventing them i.e neurotoxic metals and metal-based therapeutics
My reason was principally to reduce the scope of the topic to manageable proportions, but metal ions seem to play an important part in neuronal cell death and a better understanding of their properties could lead to improved therapeutics
The toxicity of divalent and trivalent metal ions is likely to be exerted on a wide range of different targets and intervention strategies should reflect this

Summary

Introduction

Rather than describe the role of metal ions in normal neuronal function, have focused on abnormal neuronal conditions and the role of metal ions in causing or in preventing them i.e neurotoxic metals and metal-based therapeutics. Excessive stimulation of post-synaptic glutamate receptors leads to marked depolarization, and relief of the voltage-dependent block of NMDA receptors This class, unlike the majority of AMPA/KA receptors, allows Ca2+ entry[12], and under these conditions the excess of intracellular Ca2+ overwhelms the buffering capacity of mitochondrial storage and sets in motion a train of events which leads, eventually, to cell death. What is clear is that the affected area can be protected, at least in animal models, by blockade of the NMDA receptor and recent clinical data suggest that such a strategy may be effective in man[11] Another metal ion has been implicated in neuronal damage after transient forebrain ischaemia. It has been known for some time that Zn2+ is present in the terminals of central excitatory neurones and is Zn2+ is uncertain released along but it is known with that itglcuatnamacatteasduarninignhniboirtmoar lofspyonsatp-tsiycntarptaincsmNiMssDiAo’nanTdheGArBolAe-oAf

Ian Ragan

Conclusions