Cu/Zn superoxide dismutase (SOD1) mutations are associated with amyotrophic lateral sclerosis (ALS). SOD1-positive aggregates in motor neurons, as well as proteins that interact with the aggregates are presumably involved in ALS neurotoxicity. We used a proteomics approach to compare differences in protein expression in spinal cord homogenates from non-transgenic (NTG) and ALS model mice. Using the homogenates, we identified proteins that interacted with SOD1 seeds in vitro. We assessed differences in SOD1-interacting proteins in cell cultures treated with proteasome or autophagy inhibitor. In the first experiment, intermediate filamentous and small heat shock proteins were upregulated in glial cells. We identified 26 protein types that interacted with aggregation cores in ALS model homogenates, and unexpectedly, 40 proteins in were detected in NTG mice. In cell cultures treated with proteasome and autophagy inhibitors, we identified 16 and 11 SOD1-interacting proteins, respectively, and seven proteins in untreated cells. These SOD1-interacting proteins were involved in multiple cellular functions such as protein quality control, cytoskeletal organization, and pathways involved in growth factor signaling and their downstream cascades. The complex interactions between pathways could cause further dysregulation, ultimately leading to fatal cellular dysfunction in ALS.

Cu/Zn 超氧化物歧化酶 ( SOD1 ) 突变与肌萎缩侧索硬化 (ALS) 相关。运动神经元中的 SOD1 阳性聚集体以及与聚集体相互作用的蛋白质可能与 ALS 神经毒性有关。我们使用蛋白质组学方法来比较来自非转基因 (NTG) 和 ALS 模型小鼠的脊髓匀浆中蛋白质表达的差异。使用匀浆，我们在体外鉴定了与 SOD1 种子相互作用的蛋白质. 我们评估了用蛋白酶体或自噬抑制剂处理的细胞培养物中 SOD1 相互作用蛋白的差异。在第一个实验中，中间丝状和小热休克蛋白在神经胶质细胞中上调。我们鉴定了 26 种与 ALS 模型匀浆中的聚集核心相互作用的蛋白质类型，并且意外地在 NTG 小鼠中检测到了 40 种蛋白质。在用蛋白酶体和自噬抑制剂处理的细胞培养物中，我们分别鉴定了 16 种和 11 种 SOD1 相互作用蛋白，以及未处理细胞中的 7 种蛋白质。这些与 SOD1 相互作用的蛋白质参与多种细胞功能，例如蛋白质质量控​​制、细胞骨架组织和涉及生长因子信号传导及其下游级联的通路。通路之间复杂的相互作用可能导致进一步的失调，