Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis, and death. Although its neuropathology is well investigated, currently, effective treatments are unavailable. The mechanism of ALS involves the aggregation and accumulation of several mutant proteins, including mutant copper‑zinc superoxide dismutase (SOD1), TAR DNA binding protein 43 kDa (TDP-43) and fused in sarcoma (FUS) proteins. Previous reports have shown that excessive oxidative stress, associated with mitochondrial dysfunction and mutant protein accumulation, contributes to ALS pathology. The present study focuses on the promotion of SOD1 misfolding and aggregation by oxidative stress. Having recently synthesized novel organic gem-dihydroperoxides (DHPs) with high anti-oxidant activity, we now examined whether DHPs reduce the mutant SOD1-induced intracellular aggregates involved in oxidative stress. We found that, among DHPs, 12AC2O significantly inhibited mutant SOD1-induced cell death and reduced the intracellular mutant SOD1 aggregates. Moreover, immunofluorescence staining with redox-sensitive dyes showed that 12AC2O reduced the excessive level of intracellular mutant SOD1-induced reactive oxygen species (ROS). Additionally, ESR analysis showed that 12AC2O exerts a direct scavenging effect against the hydroxyl radical (OH) and the superoxide anion (O₂₋). These results suggest that 12AC2O is a very useful agent in combination with other agents against ALS.

肌萎缩性侧索硬化症（ALS）是一种神经退行性疾病，其特征是进行性肌肉无力，麻痹和死亡。尽管对其神经病理学进行了充分的研究，但目前尚无有效的治疗方法。ALS的机制涉及几种突变蛋白的聚集和积累，包括突变铜锌超氧化物歧化酶（SOD1），TAR DNA结合蛋白43 kDa（TDP-43）和融合在肉瘤（FUS）蛋白中。先前的报道表明，与线粒体功能障碍和突变蛋白积聚相关的过度氧化应激可导致ALS病理。本研究的重点是通过氧化应激促进SOD1错折叠和聚集。最近合成了具有高抗氧化活性的新型有机宝石二氢过氧化物（DHP），我们现在检查了DHPs是否能减少突变型SOD1诱导的细胞内聚集体的氧化应激。我们发现，在DHP中，12AC2O显着抑制了突变型SOD1诱导的细胞死亡并减少了细胞内突变型SOD1的聚集。此外，氧化还原敏感染料的免疫荧光染色表明12AC2O减少了细胞内突变型SOD1诱导的活性氧（ROS）的过量水平。此外，ESR分析表明12AC2O对羟基自由基具有直接清除作用（氧化还原敏感染料的免疫荧光染色显示12AC2O减少了细胞内突变型SOD1诱导的活性氧（ROS）的过量水平。此外，ESR分析表明12AC2O对羟基自由基具有直接清除作用（氧化还原敏感染料的免疫荧光染色显示12AC2O减少了细胞内突变型SOD1诱导的活性氧（ROS）的过量水平。此外，ESR分析表明12AC2O对羟基自由基具有直接清除作用（OH）和超氧阴离子（O _{2 -} ）。这些结果表明，12AC2O与其他抗ALS药物联合使用是非常有用的药物。