Antiapoptotic Properties of Rasagiline, N‐Propargylamine‐1(R)‐aminoindan, and Its Optical (S)‐Isomer, TV1022
Antiapoptotic Properties of Rasagiline, N‐Propargylamine‐1(R)‐aminoindan, and Its Optical (S)‐Isomer, TV1022
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雷沙吉兰、N-丙炔胺-1(R)-氨基茚满及其光学 (S)-异构体、TV1022 的抗凋亡特性
DOI：
10.1111/j.1749-6632.2001.tb03641.x
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发表时间：
2001
影响因子：
5.2
通讯作者：
M. Naoi
中科院分区：
文献类型：
--
作者：
W. Maruyama;M. Youdim;M. Naoi
摘要：雷沙吉兰和结构相关的丙胺保护多巴胺能SH - SY5Y细胞免受6 - OHDA和过氧亚硝酸盐生成的SIN - 1诱导的凋亡。利用荧光指示剂JC‐1提示，神经保护的细胞内机制与线粒体膜电位的稳定有关。即使在分离的线粒体中，雷沙吉兰也能阻止通透性过渡孔（PTP）的打开。氧化应激和神经毒素对凋亡级联的激活，如caspase 3的激活和DNA的断裂，也被雷沙吉兰预处理抑制。这些丙胺可以预防或挽救由线粒体凋亡级联引起的神经元衰退，并可能作为“神经保护剂”适用于衰老和年龄相关的神经退行性疾病，如帕金森病和阿尔茨海默病。
Abstract: Rasagiline and structurally related propargylamines protected dopaminergic SH‐SY5Y cells from apoptosis induced by 6‐OHDA and peroxynitrite‐generating SIN‐1. It was suggested that the intracellular mechanism of the neuroprotection is related to the stabilization of mitochondrial membrane potential, as indicated by use of a fluorescent indicator, JC‐1. The opening of the permeability transition pore (PTP) was prevented by rasagiline, even in isolated mitochondria. The activation of apoptotic cascade by the oxidative stress and neurotoxins, such as activation of caspase 3 and DNA fragmentation, was also inhibited by pretreatment with rasagiline. These propargylamines may prevent or rescue declining neurons induced by mitochondrial apoptotic cascade and may be applicable as “neuroprotective agents” in aging and age‐related neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases.
丙炔苯丙胺对 DSP-4 诱导的神经毒性的保护与其对 MAO B 的抑制无关。
影响因子：
5
作者：
Finnegan,KT;Skratt,JJ;Irwin,I;DeLanney,LE;Langston,JW
通讯作者：
Langston,JW