Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies, Mumbai 56, India; Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V. M. Road, Vile Parle (W), Mumbai, India.
Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies, Mumbai 56, India.
Brain Res. 2025 Jan 1;1846:149236. doi: 10.1016/j.brainres.2024.149236. Epub 2024 Sep 12.
Excessive iron accumulation in the brain plays a significant role in neurodegenerative processes, contributing to the pathogenesis of Alzheimer's disease (AD). AD, a prominent neurological disorder affecting the central nervous system, is characterized by the accumulation of beta-amyloid (Aβ) and tau phosphorylation. This accumulation leads to the subsequent development of cognitive impairments, particularly in learning and memory functions. This study investigates the neuroprotective effects of emoxypine succinate in a zebrafish model of iron overload-induced neurodegeneration. Iron was administered to the zebrafish for 28 days to induce neurodegeneration. Following induction, Emoxypine succinate was employed as a treatment intervention for 14 days (concentrations of 4 mg/L, 8 mg/L, and 12 mg/L). Following the end of the treatment, behavioral tests (Y maze test, Novel tank test) were conducted on the zebrafish, and the biochemical (MDA, Catalase, SOD, GSH) and molecular parameters (AchE, Iron levels, IL-1β, TNF-α, CDK-5, GSK-3β, and NLRP3) of the zebrafish brain were also assessed. In the novel tank test, emoxypine succinate-treated groups exhibited significantly increased time in the upper zone (p < 0.001), higher distance travelled (p < 0.001), and shorter latency to the top (p < 0.001) compared to the negative control. Similarly, the Y-maze test revealed improved time in the novel arm (p < 0.001) and total distance travelled (p < 0.001) in treated groups versus the negative control. Assessment of oxidative stress parameters demonstrated significant reductions in oxidative stress in emoxypine succinate-treated groups. Furthermore, AChE activity decreased significantly (p < 0.001), and brain iron levels decreased substantially (p < 0.001) in treated groups, indicating positive therapeutic outcomes. Molecular analysis showed a significant reduction in pro-inflammatory markers like IL-1β, TNF-α, CDK-5, GSK-3β, and NLRP3 (p < 0.001). This comprehensive study highlights the potential efficacy of emoxypine succinate in mitigating neurodegeneration associated with iron dysregulation.
过量的铁在大脑中的积累在神经退行性过程中起着重要作用，导致阿尔茨海默病（AD）的发病机制。AD 是一种影响中枢神经系统的突出神经疾病，其特征是β-淀粉样蛋白（Aβ）和 tau 磷酸化的积累。这种积累导致随后认知功能障碍的发展，特别是在学习和记忆功能方面。本研究探讨了琥珀酸依莫必利在铁过载诱导的神经退行性斑马鱼模型中的神经保护作用。用铁处理斑马鱼 28 天以诱导神经退行性变。诱导后，用琥珀酸依莫必利作为治疗干预 14 天（浓度为 4mg/L、8mg/L 和 12mg/L）。治疗结束后，对斑马鱼进行行为测试（Y 迷宫测试、新鱼缸测试），并评估斑马鱼大脑的生化（MDA、Catalase、SOD、GSH）和分子参数（AchE、铁水平、IL-1β、TNF-α、CDK-5、GSK-3β 和 NLRP3）。在新鱼缸测试中，琥珀酸依莫必利处理组在上区的停留时间明显增加（p<0.001），运动距离明显增加（p<0.001），到达顶部的潜伏期明显缩短（p<0.001），与阴性对照组相比。同样，Y 迷宫测试显示，与阴性对照组相比，处理组在新臂中的停留时间（p<0.001）和总运动距离（p<0.001）均有所提高。氧化应激参数评估表明，琥珀酸依莫必利处理组的氧化应激显著降低。此外，琥珀酸依莫必利处理组 AChE 活性显著降低（p<0.001），脑铁水平显著降低（p<0.001），表明治疗效果良好。分子分析显示，促炎标志物如 IL-1β、TNF-α、CDK-5、GSK-3β 和 NLRP3 显著减少（p<0.001）。这项全面的研究强调了琥珀酸依莫必利在减轻铁失调相关神经退行性变方面的潜在疗效。
