Laboratory of Experimental Neurobiology, IRCCS, National Neurological Institute C. Mondino, Via Mondino, 2, 27100 Pavia, Italy.
Cell Signal. 2010 Oct;22(10):1477-84. doi: 10.1016/j.cellsig.2010.05.016. Epub 2010 May 31.
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative multifactorial disease characterized, like other diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) or frontotemporal dementia (FTD), by the degeneration of specific neuronal cell populations. Motor neuron loss is distinctive of ALS. However, the causes of onset and progression of motor neuron death are still largely unknown. In about 2% of all cases, mutations in the gene encoding for the Cu/Zn superoxide dismutase (SOD1) are implicated in the disease. Several alterations in the expression or activation of cell cycle proteins have been described in the neurodegenerative diseases and related to cell death. In this work we show that mutant SOD1 can alter cell cycle in a cellular model of ALS. Our findings suggest that modifications in the cell cycle progression could be due to an increased interaction between mutant G93A SOD1 and Bcl-2 through the cyclins regulator p27. As previously described in post mitotic neurons, cell cycle alterations could fatally lead to cell death.
肌萎缩侧索硬化症（ALS）是一种神经退行性多因素疾病，与阿尔茨海默病（AD）、帕金森病（PD）或额颞叶痴呆（FTD）等其他疾病一样，其特征是特定神经元细胞群体的退化。运动神经元的丧失是 ALS 的特征。然而，运动神经元死亡的发病和进展的原因在很大程度上仍然未知。在所有病例中约有 2%，编码铜/锌超氧化物歧化酶（SOD1）的基因突变与该疾病有关。在神经退行性疾病及其相关的细胞死亡中，已经描述了细胞周期蛋白的表达或激活的几种改变。在这项工作中，我们表明突变型 SOD1 可以在 ALS 的细胞模型中改变细胞周期。我们的研究结果表明，细胞周期进展的改变可能是由于突变型 G93A SOD1 与 Bcl-2 之间通过细胞周期蛋白调节因子 p27 的相互作用增加所致。正如先前在有丝分裂后神经元中所描述的那样，细胞周期的改变可能会导致致命的细胞死亡。
