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Neuroprotection by deprenyl
and related compounds
Maruyama W, Naoi M
Department of Basic Gerontology,
National Institute for Longevity Sciences Obu, Japan.
maruyama@nils.go.jp
Mech Ageing Dev 1999 Nov; 111(2-3):189-200
ABSTRACT
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.
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