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Neuroprotection by (-)-deprenyl and related compounds. There is an increasing number of data by in vitro and in vivo experiments, indicating that (-)-deprenyl is neuroprotective to dopamine neurons, even though detailed mechanism remains to be clarified. In this paper neuroprotection by (-)-deprenyl and structurally related compounds was examined in concern with the suppression of apoptosis induced by a reactive oxygen species, peroxynitrite generated from SIN-1. The apoptotic DNA damage was quantitatively determined using dopaminergic SH-SYSY cells and by a single cell gel electrophoresis (comet) assay. DNA damage induced by peroxynitrite was proved to be apoptotic by prevention of the damage by cycloheximide or actinomycin-D. (-)-Deprenyl and other propargylamines protected the cells from apoptosis in a dose-dependent way. (-)-Deprenyl protected the cells even after it was washed out, suggesting that it may initiate the intracellular process to repress the apoptotic death program. The study on the structure-activity relationship of (-)-deprenyl analogues revealed that a N-propargyl residue with adequate size of hydrophobic structure is essentially required for the anti-apoptotic activity. These results suggest that (-)-deprenyl and related compounds may protect neurons from apoptosis and be applicable to delay the deterioration of neurons during advancing ageing and in neurodegenerative disorders. Mech Ageing Dev 1999 Nov;111(2-3):189-200 Maruyama W, Naoi M Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Japan. [log in to unmask] PMID: 10656536 http://www.ncbi.nlm.nih.gov/PubMed/ janet paterson, an akinetic rigid subtype parkie 53 now / 44 dx cd / 43 onset cd / 41 dx pd / 37 onset pd TEL: 613 256 8340 SMAIL: PO Box 171 Almonte Ontario K0A 1A0 Canada EMAIL: [log in to unmask] URL: http://www.geocities.com/janet313/