Wang Shiyao, Xu Zhaohan, Wang Siyu, Peng Qiang, Zhu Siqi, Liu Caidong, Zhang Yingdong, Duan Rui
Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210006, Jiangsu, People's Republic of China.
Neurochem Res. 2025 Aug 25;50(5):277. doi: 10.1007/s11064-025-04531-7.
Alzheimer's disease (AD) is on the rise worldwide, consequently driving a growing demand for effective prevention and treatment strategies. Alamandine is a member of the renin-angiotensin system family. Although alamandine exhibits protective effects in the pathophysiology of various disorders, its role in AD remains an unexplored area. This research aims to elucidate the benefits and mechanisms of alamandine in an in vivo model of AD. The mice received intracerebroventricular injections of vehicle or alamandine once daily for 4 weeks. The Morris water maze was conducted to assess spatial learning ability. Nissl staining was performed to evaluate neuronal injury. Important inflammation indictors were detected both by qRT-PCR and ELISA. Representative oxidative stress indicators and Fe levels were measured using corresponding assay kits. Western blot was employed to detect the expression levels of the related proteins. We found that alamandine mitigates cognitive function and spatial learning impairment in APP/PS1 mice. Alamandine shows positive therapeutic effects by ameliorating the phosphorylation of tau proteins and suppressing neuroinflammation. In addition, alamandine mitigates the oxidative stress, ferroptosis and endoplasmic reticulum stress (ERS) in the brain of APP/PS1 mice. Our research indicates that alamandine alleviates cognitive impairment in APP/PS1 mice and inhibits inflammation, oxidative stress, ferroptosis, and ERS. It may serve as a promising approach to alleviate symptoms and promote remission in AD.
阿尔茨海默病（AD）在全球范围内呈上升趋势，因此对有效预防和治疗策略的需求日益增长。阿拉曼丁是肾素-血管紧张素系统家族的一员。尽管阿拉曼丁在各种疾病的病理生理学中表现出保护作用，但其在AD中的作用仍是一个未被探索的领域。本研究旨在阐明阿拉曼丁在AD体内模型中的益处和作用机制。小鼠每天接受一次脑室内注射溶剂或阿拉曼丁，持续4周。进行莫里斯水迷宫实验以评估空间学习能力。进行尼氏染色以评估神经元损伤。通过qRT-PCR和ELISA检测重要的炎症指标。使用相应的检测试剂盒测量代表性的氧化应激指标和铁水平。采用蛋白质印迹法检测相关蛋白的表达水平。我们发现阿拉曼丁可减轻APP/PS1小鼠的认知功能和空间学习障碍。阿拉曼丁通过改善tau蛋白的磷酸化和抑制神经炎症显示出积极的治疗效果。此外，阿拉曼丁可减轻APP/PS1小鼠大脑中的氧化应激、铁死亡和内质网应激（ERS）。我们的研究表明，阿拉曼丁可减轻APP/PS1小鼠的认知障碍，并抑制炎症、氧化应激、铁死亡和ERS。它可能是一种缓解AD症状和促进病情缓解的有前景的方法。
