Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
Oxid Med Cell Longev. 2020 Jan 29;2020:1020673. doi: 10.1155/2020/1020673. eCollection 2020.
Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder characterized by progressive paralysis resulting from the death of upper and lower motor neurons. There is currently no effective pharmacological treatment for ALS, and the two approved drugs riluzole and edaravone have limited effects on the symptoms and only slightly prolong the life of patients. Therefore, the development of effective therapeutic strategies is of paramount importance. In this study, we investigated whether Miyako Island (MBP) can alleviate the neurological deterioration observed in a superoxide dismutase-1 G93A mutant transgenic mouse (G93A mouse) model of ALS. We orally administered 2 g/kg/day of MBP to G93A mice at the onset of symptoms of neurodegeneration (15 weeks old) until death. Treatment with MBP markedly prolonged the life of ALS model mice by approximately 20 days compared to that of vehicle-treated ALS model mice and significantly improved motor performance. MBP treatment prevented the reduction in SMI32 expression, a neuronal marker protein, and attenuated astrocyte (detected by GFAP) and microglia (detected by Iba-1) activation in the spinal cord of G93A mice at the end stage of the disease (18 weeks old). Our results indicate that MBP administered after the onset of ALS symptoms suppressed the inflammatory activation of microglia and astrocytes in the spinal cord of the G93A ALS model mice, thus improving their quality of life. MBP may be a potential therapeutic agent for ALS.
肌萎缩侧索硬化症（ALS）是一种迟发性神经退行性疾病，其特征是由于上下运动神经元的死亡而导致进行性瘫痪。目前，ALS 没有有效的药物治疗方法，两种已批准的药物利鲁唑和依达拉奉对症状的影响有限，只能略微延长患者的生命。因此，开发有效的治疗策略至关重要。在这项研究中，我们研究了 Miyako 岛（MBP）是否可以减轻在超氧化物歧化酶-1 G93A 突变转基因小鼠（G93A 小鼠）ALS 模型中观察到的神经退行性变恶化。我们在神经退行性变症状出现时（15 周龄）开始以 2g/kg/天的剂量经口给予 G93A 小鼠 MBP，直至死亡。与用载体处理的 ALS 模型小鼠相比，MBP 治疗使 ALS 模型小鼠的寿命延长了约 20 天，并且显著改善了运动性能。MBP 治疗可防止 SMI32 表达（神经元标志物蛋白）的减少，并在疾病末期（18 周龄）减轻 G93A 小鼠脊髓中星形胶质细胞（GFAP 检测）和小胶质细胞（Iba-1 检测）的激活。我们的结果表明，在 ALS 症状出现后给予 MBP 可抑制 G93A ALS 模型小鼠脊髓中小胶质细胞和星形胶质细胞的炎症激活，从而提高其生活质量。MBP 可能是 ALS 的一种潜在治疗剂。
