The Parkinson's Institute, Department of Basic Research, Sunnyvale, CA, USA.
FEBS Lett. 2013 May 21;587(10):1562-70. doi: 10.1016/j.febslet.2013.04.001. Epub 2013 Apr 13.
Loss of DJ-1 function contributes to pathogenesis in Parkinson's disease. Here, we investigate the impact of aging and DJ-1 deficiency in transgenic mice. Ventral midbrain from young DJ-1-deficient mice revealed no change in 4-hydroxy-2-nonenal (4-HNE), but HSP60, HSP40 and striatal dopamine turnover were significantly elevated compared to wildtype. In aged mice, the chaperone response observed in wildtype animals was absent from DJ-1-deficient transgenics, and nigral 4-HNE immunoreactivity was enhanced. These changes were concomitant with increased striatal dopamine levels and uptake. Thus, increased oxidants and diminished protein quality control may contribute to nigral oxidative damage with aging in the model.
DJ-1 功能丧失导致帕金森病的发病机制。在这里，我们研究了衰老和 DJ-1 缺乏对转基因小鼠的影响。年轻的 DJ-1 缺陷型小鼠的中脑腹侧未见 4-羟基-2-壬烯醛 (4-HNE) 改变，但热休克蛋白 60 (HSP60)、热休克蛋白 40 (HSP40) 和纹状体多巴胺周转率明显高于野生型。在老年小鼠中，野生型动物中观察到的伴侣蛋白反应在 DJ-1 缺陷型转基因动物中缺失，黑质 4-HNE 免疫反应增强。这些变化伴随着纹状体多巴胺水平和摄取的增加。因此，随着年龄的增长，模型中增加的氧化剂和降低的蛋白质质量控制可能导致黑质氧化损伤。
