Is selegiline neuroprotective in Parkinson's disease?
Recent findings emphasize the significance of oxidative mechanisms, involving the activity of monoamine oxidase (MAO) and the formation of free radicals, in the pathogenesis of Parkinson's disease. The possible role of such mechanisms in the degeneration of neurones in the substantia nigra has led to clinical trials aimed at preventing or slowing the progressively disabling course of the disease. However, conclusive clinical evidence of a neuroprotective effect in PD is still lacking. In this paper, we discuss possible mechanisms by which selegiline manifests neuroprotective effects in experimental and clinical situations. Besides MAO-B inhibition, which above all explains the prevention of protoxin activation and substrate oxidation by MAO-B, selegiline appears to exhibit other mechanisms of action (induction of superoxide dismutase, stimulation of neurotrophic factor synthesis, antagonistic modulation of the polyamine binding site of the NMDA-receptor) which are independent of its action on MAO-B.
Gerlach
M
M
Department of Psychiatry, University of Würzburg, Federal Republic of Germany.
Youdim
M B
MB
Riederer
P
P
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004790:Enzyme Induction / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D010300:Parkinson Disease / Q000188:drug therapy*; D012642:Selegiline / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins; D012642:Selegiline; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D008995:Monoamine Oxidase