Magalhães Rayne S S, Monteiro Neto José R, Ribeiro Gabriela D, Paranhos Luan H, Eleutherio Elis C A
Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil.
Antioxidants (Basel). 2024 Jul 3;13(7):807. doi: 10.3390/antiox13070807.
This work aimed to study the effect of trehalose in protecting cells against Sod1 proteinopathy associated with amyotrophic lateral sclerosis (ALS). Humanized yeast cells in which native Sod1 was replaced by wild-type human Sod1 or an ALS mutant (WT-A4V Sod1 heterodimer) were used as the experimental model. Cells were treated with 10% trehalose (p/v) before or after the appearance of hSod1 proteinopathy induced by oxidative stress. In both conditions, trehalose reduced the number of cells with Sod1 inclusions, increased Sod1 activity, and decreased the levels of intracellular oxidation, demonstrating that trehalose avoids Sod1 misfolding and loss of function in response to oxidative stress. The survival rates of ALS Sod1 cells stressed in the presence of trehalose were 60% higher than in their absence. Treatment with trehalose after the appearance of Sod1 inclusions in cells expressing WT Sod1 doubled longevity; after 5 days, non-treated cells did not survive, but 15% of cells treated with sugar were still alive. Altogether, our results emphasize the potential of trehalose as a novel therapy, which might be applied preventively in ALS patients with a family history of the disease or after diagnosis in ALS patients who discover the disease following the first symptoms.
这项工作旨在研究海藻糖在保护细胞免受与肌萎缩侧索硬化症（ALS）相关的Sod1蛋白病影响方面的作用。将天然Sod1被野生型人Sod1或ALS突变体（WT-A4V Sod1异二聚体）取代的人源化酵母细胞用作实验模型。在氧化应激诱导hSod1蛋白病出现之前或之后，用10%海藻糖（质量/体积）处理细胞。在这两种情况下，海藻糖都减少了含有Sod1包涵体的细胞数量，增加了Sod1活性，并降低了细胞内氧化水平，表明海藻糖可避免Sod1在氧化应激反应中错误折叠和功能丧失。在有海藻糖存在的情况下受到应激的ALS Sod1细胞的存活率比没有海藻糖时高60%。在表达WT Sod1的细胞中出现Sod1包涵体后用海藻糖处理，细胞寿命延长了一倍；5天后，未处理的细胞无法存活，但15%接受糖类处理的细胞仍然存活。总之，我们的结果强调了海藻糖作为一种新疗法的潜力，它可能被预防性地应用于有该疾病家族史的ALS患者，或在首次出现症状后被诊断出疾病的ALS患者确诊后应用。
