Amyotrophic lateral sclerosis (ALS) is a fatal multisystem degenerative disorder with minimal available therapeutic. However, some recent studies showed promising results of immunological-based treatment. Here, we aimed to evaluate the efficacy of ibrutinib against ALS-associated abnormalities by targeting inflammation and muscular atrophy. Ibrutinib was administrated orally to SOD1 ^G93A mice from 6 to 19 weeks for prophylactic administration and 13 to 19 weeks for therapeutic administration. Our results demonstrated that ibrutinib treatment significantly delayed ALS-like symptom onset in the SOD1 ^G93A mice, as shown by improved survival time and reduced behavioral impairments. Ibrutinib treatment significantly reduced muscular atrophy by increasing muscle/body weight and decreasing muscular necrosis. The ibrutinib treatment also considerably reduced pro-inflammatory cytokine production, IBA-1, and GFAP expression, possibly mediated by mTOR/Akt/Pi3k signaling in the medulla, motor cortex and spinal cord of the ALS mice. In conclusion, our study demonstrated that ibrutinib could delay ALS onset, increase survival time, and reduce ALS progression by targeting inflammation and muscular atrophy via mTOR/Akt/PI3K modulation.

肌萎缩侧索硬化症 (ALS) 是一种致命的多系统退行性疾病，可用的治疗方法很少。然而，最近的一些研究显示了基于免疫学的治疗的有希望的结果。在这里，我们的目的是通过针对炎症和肌肉萎缩来评估依鲁替尼对 ALS 相关异常的疗效。^{SOD1 G93A}小鼠在 6 至 19 周内口服依鲁替尼进行预防性给药，在 13 至 19 周内进行治疗性给药。^{我们的结果表明，依鲁替尼治疗显着延迟了 SOD1 G93A}小鼠的 ALS 样症状发作，表现为生存时间延长和行为障碍减少。依鲁替尼治疗通过增加肌肉/体重和减少肌肉坏死来显着减少肌肉萎缩。依鲁替尼治疗还显着减少了促炎细胞因子的产生、IBA-1 和 GFAP 的表达，这可能是由 ALS 小鼠髓质、运动皮层和脊髓中的 mTOR/Akt/Pi3k 信号传导介导的。总之，我们的研究表明，依鲁替尼可以通过 mTOR/Akt/PI3K 调节靶向炎症和肌肉萎缩，从而延迟 ALS 发病、延长生存时间并减少 ALS 进展。