Spadoni Ornella, Crestini Alessio, Piscopo Paola, Malvezzi-Campeggi Lorenzo, Carunchio Irene, Pieri Massimo, Zona Cristina, Confaloni Annamaria
Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina, Elena 299, Rome, Italy.
Cell Mol Neurobiol. 2009 Jul;29(5):635-41. doi: 10.1007/s10571-009-9356-8. Epub 2009 Feb 13.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease defined by motor neuron loss. Transgenic mouse model (Tg SOD1G93A) shows pathological features that closely mimic those seen in ALS patients. An hypothetic link between AD and ALS was suggested by finding an higher amount of amyloid precursor protein (APP) in the spinal cord anterior horn neurons, and of Abeta peptides in ALS patients skin. In this work, we have investigated the expression of some genes involved in Alzheimer's disease, as APP, beta- and gamma-secretase, in an animal model of ALS, to understand some possible common molecular mechanisms between these two pathologies. For gene expression analysis, we carried out a quantitative RT-PCR in ALS mice and in transgenic mice over-expressing human wild-type SOD1 (Tg hSOD1). We found that APP and BACE1 mRNA levels were increased 1.5-fold in cortical cells of Tg SOD1G93A mice respect to Tg hSOD1, whereas the expression of gamma-secretase genes, as PSEN1, PSEN2, Nicastrin, and APH1a, showed no statistical differences between wild-type and ALS mice. Biochemical analysis carried out by immunostaining and western blotting, did not show any significant modulation of the protein expression compared to the genes, suggesting the existence of post-translational mechanisms that modify protein levels.
肌萎缩侧索硬化症（ALS）是一种由运动神经元丧失所定义的进行性神经退行性疾病。转基因小鼠模型（Tg SOD1G93A）显示出与ALS患者所见极为相似的病理特征。在ALS患者的脊髓前角神经元中发现了较高水平的淀粉样前体蛋白（APP），在其皮肤中发现了较高水平的β淀粉样肽，这提示了AD与ALS之间可能存在某种联系。在这项研究中，我们在一种ALS动物模型中研究了一些与阿尔茨海默病相关的基因的表达，如APP、β和γ分泌酶，以了解这两种疾病之间可能存在的共同分子机制。为了进行基因表达分析，我们对ALS小鼠和过表达人野生型SOD1的转基因小鼠（Tg hSOD1）进行了定量逆转录聚合酶链反应（RT-PCR）。我们发现，相对于Tg hSOD1，Tg SOD1G93A小鼠皮质细胞中的APP和BACE1 mRNA水平增加了1.5倍，而γ分泌酶基因（如PSEN1、PSEN2、尼卡斯特林和APH1a）的表达在野生型小鼠和ALS小鼠之间没有统计学差异。通过免疫染色和蛋白质印迹法进行的生化分析表明，与基因相比，蛋白质表达没有任何显著的调节变化，这表明存在修饰蛋白质水平的翻译后机制。
