Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 130-701, South Korea.
Department of Physiology, School of Medicine, Neurodegeneration Control Research Center, Kyung Hee University, Seoul, 130-701, South Korea.
Arch Pharm Res. 2016 Aug;39(8):1144-50. doi: 10.1007/s12272-016-0798-5. Epub 2016 Jul 27.
Superoxide dismutase 1 (SOD1) is a well-known antioxidant enzyme. Mutation of SOD1 is closely associated with the pathogenesis of neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer's disease. However, the pathologic pathways linking neurodegenerative diseases with mutation of SOD1 remain elusive. Here, we investigated the motility of SOD1-WT and -G93A (a pathogenic mutant of SOD1), and observed correlation of axonal transport of the mutant protein with mitochondria in primary cultured hippocampal neurons. The SOD1-G93A mutant showed significant accumulation at vGlut1-positive synaptic boutons and in cell bodies, compared to SOD1-WT. The proportions of motile WT and G93A proteins were similar (30 %) while the motility velocity of SOD1-G93A was significantly slower (40 %) than that of the WT counterpart. This motility defect of SOD1-G93A was highly correlated with mitochondrial movement. Our results collectively suggest that the SOD1-G93A mutant has a defect in motility that is linked to mitochondrial transport in axons.
超氧化物歧化酶 1（SOD1）是一种众所周知的抗氧化酶。SOD1 的突变与神经退行性疾病的发病机制密切相关，如肌萎缩侧索硬化症和阿尔茨海默病。然而，将神经退行性疾病与 SOD1 突变联系起来的病理途径仍不清楚。在这里，我们研究了 SOD1-WT 和 -G93A（SOD1 的一种致病性突变体）的运动性，并观察了原代培养海马神经元中突变蛋白的轴突运输与线粒体的相关性。与 SOD1-WT 相比，SOD1-G93A 突变体在 vGlut1 阳性突触末梢和细胞体中明显积聚。WT 和 G93A 蛋白的运动比例相似（约 30%），而 SOD1-G93A 的运动速度明显较慢（约 40%）。这种 SOD1-G93A 的运动缺陷与线粒体运动高度相关。我们的研究结果表明，SOD1-G93A 突变体在运动性方面存在缺陷，与轴突中的线粒体运输有关。
