A molecular mechanism regulating pathological aggregation of SOD1 proteins

als引起的突变促进了SOD1的聚集，因此SOD1的结构发生了显著变化；然而，蛋白质聚集体的结构仍然不清楚。在这里，通过质谱分析，我在野生型和引起als的突变SOD1聚集体中鉴定了一个蛋白酶抗性核心。SOD1聚集体表现出突变依赖的结构多态性，这进一步调节了聚集体的生化特性，如溶解度。基于这些结果，我提出了一种新的fALS发病机制，其中SOD1聚集体的突变依赖性结构多态性可以影响疾病表型。

ALS-causing mutations facilitate aggregation of SOD1, upon which significant structural changes of SOD1 have been assumed; however, a structure of protein aggregate remains obscure. Here, by utilizing mass spectrometry, I have identified a protease-resistant core in wild-type as well as ALS-causing mutant SOD1 aggregates. SOD1 aggregates exhibit mutation-dependent structural polymorphism, which further regulates biochemical properties of aggregates such as solubility. Based upon these results, I propose a new pathomechanism of fALS in which mutation-dependent structural polymorphism of SOD1 aggregates can affect disease phenotypes.