Wu R M, Murphy D L, Chiueh C C
Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Ann N Y Acad Sci. 1996 Jun 15;786:379-90. doi: 10.1111/j.1749-6632.1996.tb39078.x.
The present study clearly demonstrated that l-deprenyl confers a substantial protective effect against MPP+ in the substantia nigra zona compacta in vivo. 32.39. The protection provided by l-deprenyl may not depend on its inhibition of type B monoamine oxidase. A unique antioxidant property of l-deprenyl by suppression of cycotoxic. OH formation and associated oxidative damage induced by MPP+ in the A9 melanized nigral neurons may contribute to the protection against MPP+ toxicity in the nigrostriatal system. The likelihood that l-deprenyl may confer neuroprotection against MPP+ toxicity through antioxidant effect is further strongly supported by our recent data that U-78517F (2-methlaminochromans) a potent inhibitor of ironcatalyzed lipid peroxidation, and DMSO an effective. OH scavenger also protect nigral neurons against MPP(+)-induced severe oxidative injury in the substantia nigra. This putative antioxidant effect of deprenyl may explore another mechanism which may in part contribute to its overt neuroprotection against several toxins, including 6-OHDA, DSP-4, and MPTP, and the possible clinical effects on slowing the neuronal degeneration in early Parkinson's disease, Alzheimer's disorder and even senescent changes.
本研究清楚地表明，左旋司来吉兰在体内对黑质致密部的MPP+具有显著的保护作用。32.39。左旋司来吉兰提供的保护作用可能不依赖于其对B型单胺氧化酶的抑制。左旋司来吉兰通过抑制细胞毒性·OH的形成以及MPP+在A9黑质黑色素神经元中诱导的相关氧化损伤所具有的独特抗氧化特性，可能有助于保护黑质纹状体系统免受MPP+毒性的影响。我们最近的数据进一步有力地支持了左旋司来吉兰可能通过抗氧化作用对MPP+毒性产生神经保护作用这一观点，即U-78517F（2-甲氨基苯并二氢吡喃）是铁催化脂质过氧化的有效抑制剂，二甲基亚砜是有效的·OH清除剂，它们也能保护黑质神经元免受MPP(+)在黑质中诱导的严重氧化损伤。司来吉兰这种假定的抗氧化作用可能揭示了另一种机制，该机制可能部分有助于其对包括6-羟基多巴胺、DSP-4和MPTP在内的多种毒素的明显神经保护作用，以及对减缓早期帕金森病、阿尔茨海默病甚至衰老变化中的神经元变性可能产生的临床效果。
