Participation in ALS pathology of ALS linked mutant SOD1 proteins accumulated in MAM

SOD1是家族性肌萎缩侧索硬化症(FALS)的主要致病蛋白。我发现FALS连锁的突变体SOD1蛋白特异性地聚集在线粒体-内质网相关膜(MAM)部分。然而，这一事件的毒性机制仍不清楚。我推测，MAM的主要蛋白Sigma-1受体(Sigma-1 Receptor，SigR1)被突变的SOD1蛋白在MAM中的积累所抑制。在本研究中，我发现了两个新的发现：(1)SigR1与Kv2.1和Kv4.2直接相互作用；(2)SigR1与Kv2.1的定位有关。虽然我需要对这些结果进行更多的研究，但这些发现可能有助于阐明FALS的发病机制。

SOD1 is a major causative protein of familial amyotrophic lateral screosis (fALS). I found that fALS linked mutant SOD1 proteins are specifically accumulated in mitochondria-ER associated membrane (MAM) fraction. The toxic mechanisms by this event, however, are still unknown. I hypothesized that Sigma-1 receptor (SigR1), which is a major MAM protein was inhibited by the accumulation of mutant SOD1 proteins in MAM. In this study, I found two novel finding (1) SigR1 was directly interacted with Kv2.1 and Kv4.2 (2) SigR1 was related with the localization of Kv2.1. Although I need to investigate these results more, these findings might be contributed to elucidation of the pathomechanism of fALS.