Naoi M, Maruyama W
Department of Brain Sciences, Institute of Applied Biochemistry, Gifu, Japan.
Parkinsonism Relat Disord. 2001 Oct;8(2):139-45. doi: 10.1016/s1353-8020(01)00028-1.
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.
帕金森病中已提出神经保护疗法来挽救多巴胺能神经元。司来吉兰是神经保护候选药物之一,体内和体外实验均已证实。本文研究了司来吉兰及相关炔丙胺对多巴胺能SH-SY5Y细胞内源性毒素N-甲基(R)-salsolinol、合成的6-羟基多巴胺和过氧亚硝酸盐诱导的细胞凋亡的神经保护机制。炔丙胺通过抑制线粒体膜电位崩溃以及随后激活半胱天冬酶3并向细胞核进行信号转导,防止凋亡性DNA损伤。这些结果表明,炔丙胺可能挽救或保护帕金森病中的多巴胺能神经元。