Future of neuroprotection in Parkinson's disease.
In Parkinson's disease neuroprotective therapy to rescue dopamine neurons has been proposed. Selegiline is one of neuroprotective drug candidates, as proved by in vivo and in vitro experiments. In this paper, the mechanism underlying neuroprotection by selegiline and related propargylamines was studied against apoptosis induced by an endogenous toxin, N-methyl(R)salsolinol, synthetic 6-hydroxydopamine and peroxynitrite in dopaminergic SH-SY5Y cells. Propargylamines prevented apoptotic DNA damage, through suppression of collapse in mitochondrial membrane potential and following activation of caspase 3 and signal transduction to nuclei. These results suggest that propargylamines may rescue or protect dopamine neurons in Parkinson's disease.
Naoi
M
M
Department of Brain Sciences, Institute of Applied Biochemistry, Gifu, Japan. mnaoi@quartz.ocn.ne.jp
Maruyama
W
W
D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009498:Neurotoxins / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy*; D011437:Propylamines / Q000494:pharmacology; D012490:Salsoline Alkaloids / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology; D044005:Tetrahydroisoquinolines; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018696:Neuroprotective Agents; D009498:Neurotoxins; D020030:Nitric Oxide Donors; D011437:Propylamines; D012490:Salsoline Alkaloids; D044005:Tetrahydroisoquinolines; D012642:Selegiline; C002385:linsidomine; D016627:Oxidopamine; C032837:salsoline; D008981:Molsidomine