Department of Neurology, First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Institute of Neurology, Jiangxi Academy of Clinical Medical Science, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.
Mol Med. 2024 Nov 9;30(1):206. doi: 10.1186/s10020-024-00977-7.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss leading to muscle weakness and atrophy. Apigenin (APG), known for its antioxidant properties, holds potential as a therapeutic compound in ALS.
We used the Tg(SOD1*G93A)1Gur/J transgenic mouse model of ALS to investigate the therapeutic effects of APG. Key measured included motor function via the ALSTDI score, molecular markers of oxidative stress (OS) and apoptosis in spinal cord tissues. Techniques used included pathological, Western blotting, flow cytometry, and qRT-PCR to assess the effect of ALDH1A2.
APG treatment attenuated weight loss and improved motor function scores in ALS mice compared to untreated ALS models. Molecular analyses revealed a significant upregulation of ALDH1A2 in APG-treated groups, along with a reduction in markers of OS and apoptosis. In vitro studies in NSC34 cells further confirmed the protective effects of APG against SOD1*G93A mutation-induced cytotoxicity. In addition, suppression of ALDH1A2 by shRNA exacerbated disease markers that were ameliorated by APG treatment.
Our results suggest that APG attenuates the progression of ALS pathology by regulating OS and apoptosis through ALDH1A2. These results support further investigation of APG as a potential therapeutic agent for the treatment of ALS.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病，其特征是运动神经元丧失导致肌肉无力和萎缩。芹菜素（APG）因其抗氧化特性而具有作为 ALS 治疗化合物的潜力。
我们使用 Tg(SOD1*G93A)1Gur/J 转基因 ALS 小鼠模型来研究 APG 的治疗效果。关键测量指标包括通过 ALSTDI 评分评估的运动功能、脊髓组织中氧化应激（OS）和细胞凋亡的分子标志物。使用的技术包括病理学、Western 印迹、流式细胞术和 qRT-PCR 来评估 ALDH1A2 的影响。
与未治疗的 ALS 模型相比，APG 治疗可减轻 ALS 小鼠的体重减轻并改善运动功能评分。分子分析显示，APG 治疗组中 ALDH1A2 显著上调，同时 OS 和细胞凋亡标志物减少。在 NSC34 细胞中的体外研究进一步证实了 APG 对 SOD1*G93A 突变诱导的细胞毒性的保护作用。此外，shRNA 抑制 ALDH1A2 会加重疾病标志物，而 APG 治疗可改善这些标志物。
我们的结果表明，APG 通过调节 OS 和细胞凋亡来减轻 ALS 病理的进展，这是通过 ALDH1A2 实现的。这些结果支持进一步研究 APG 作为治疗 ALS 的潜在治疗剂。
