Huiting Liang, Xinhui Zhou, Jie Zhang, Wenyuan Xu, Yi Liu, Xinxin Wang, Yushu Hu, Renshi Xu, Xiaobing Li
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引用次数: 0
摘要
背景：肌萎缩性脊髓侧索硬化症（ALS）是一种进行性神经退行性疾病，其特征是运动神经元缺失导致肌肉无力和萎缩。芹菜素（APG）以其抗氧化特性而闻名，具有作为 ALS 治疗化合物的潜力：我们使用 Tg(SOD1*G93A)1Gur/J ALS 转基因小鼠模型来研究 APG 的治疗效果。主要测量指标包括脊髓组织中通过 ALSTDI 评分显示的运动功能、氧化应激（OS）和细胞凋亡的分子标记。采用的技术包括病理、Western印迹、流式细胞术和qRT-PCR，以评估ALDH1A2的效果：结果：与未经治疗的 ALS 模型相比，APG 治疗减轻了 ALS 小鼠的体重减轻，改善了运动功能评分。分子分析表明，在 APG 治疗组中，ALDH1A2 明显上调，同时 OS 和细胞凋亡的标记物减少。在 NSC34 细胞中进行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，通过 shRNA 抑制 ALDH1A2 会加重疾病标志物，而 APG 治疗可改善这些标志物：我们的研究结果表明，APG可通过ALDH1A2调节OS和细胞凋亡，从而减轻ALS的病理进展。这些结果支持将 APG 作为治疗 ALS 的潜在治疗药物进行进一步研究。
The therapeutic potential of Apigenin in amyotrophic lateral sclerosis through ALDH1A2/Nrf2/ARE signaling.
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍：
Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.
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