Anti-Apoptotic Function of Propargylamines
(-)Deprenyl (selegiline), an inhibitor specific to type B monoamine oxidase (MAO-B), is now clinically applied for Parkinson’s disease (PD), as an adjunct of L-DOPA therapy. Recent results have shown that selegiline (Parkinson Study Group, 1989) and structurally related propargylamines, such as (R)(+)-N-propargyl-1-aminoindan (rasagiline) and (R)-N-(2-heptyl)-N-methylpropargylamine (R-2HMP), delay the progress of the disease. However, it remains to be clarified, whether the effects are due to the neuroprotective or neurorescue effects, or only symptomatic. On the other hand, the well-controlled apoptotic cascade has been proposed to be a target of neuroprotection (Thompson, 1995), even though it requires further evidence whether apoptosis is a major type of cell death in PD (Jellinger, 2000). To elucidate this point, the mechanism underlying neuroprotection by propargylamines was examined using a cell model of apoptosis induced by endogenous N-methyl(R)salsolinol [NM(R)Sal] and peroxynitrite generating N-morpholino-sydnonimine (SIN-1) in human dopaminergic SH-SY5Y cells.
KeywordsApoptotic Cascade Parkinson Study Group Peroxynitrite Generate Endogenous Neurotoxin Multicenter Control Clinical Trial
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