Metal ions in neuroscience.
Metal ions are believed to participate in many neurodegenerative conditions. In excitotoxic cell death there is convincing evidence for the participation of Ca(2+) and Zn(2+) 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 Mg(2+)-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 Fe(2+) 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.
Ragan
C I
CI
Department of Biochemistry and Molecular Biology Neuroscience Research Centre Merck Sharp and Dohme Research Laboratories Terlings Park Harlow CM20 2QR UK.