Cui Xue-Min, Wang Wang, Yang Lin, Nie Bao-Wen, Liu Qian, Li Xiao-Hui, Duan Dong-Xiao
Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Int J Mol Sci. 2025 Apr 14;26(8):3715. doi: 10.3390/ijms26083715.
Alzheimer's disease (AD) is a progressive degenerative disease of the nervous system that affects older adults. Its main clinical manifestations include memory loss, cognitive dysfunction, abnormal behaviour, and social dysfunction. Neuroinflammation is typical in most neurodegenerative diseases, such as AD. Therefore, suppressing inflammation may improve AD symptoms. This study investigated the neuroprotective effects of in an AD model induced by streptozotocin (STZ). Here, we characterised a rat model of STZ-induced AD with the parallel deterioration of memory loss and neuroinflammation. Following the end of the treatment with ASS (50 mg/kg for 14 consecutive days), behavioural tests (Morris water maze test, Y-maze test) were performed on the rat, and the molecular parameters (DAPK1, Tau5, p-Tau, NF-κB, IL-1β, TNF-α, and NLRP3) of the rat hippocampus were also assessed. We demonstrated that ASS, which has potent anti-inflammatory effects, can reduce neuroinflammation and prevent cognitive impairment. In the water maze test, ASS-treated groups exhibited significantly increased average escape latency ( < 0.05), the percentage of stay in the target quadrant ( < 0.05), and the number of times each group of rats crossed the platform ( < 0.05) compared to the negative control. And ASS could reduce the phosphorylation of the Tau protein ( < 0.001) and death-associated protein kinase 1 (DAPK1, < 0.001) in the hippocampal tissue, improving cognitive impairment in STZ-treated rats by suppressing the inflammatory response; the molecular analysis showed a significant reduction in pro-inflammatory markers like NLRP3, IL-1β, TNF-α, and NF-κB ( < 0.001). It was also discovered that the NF-κB inhibitor SN50 had the same effect. Therefore, the present study used ASS through its anti-inflammatory effects to prevent and treat AD. This study highlights the potential efficacy of ASS in alleviating cognitive dysfunction in AD.
阿尔茨海默病（AD）是一种影响老年人的进行性神经系统退行性疾病。其主要临床表现包括记忆力丧失、认知功能障碍、行为异常和社交功能障碍。神经炎症在大多数神经退行性疾病中都很典型，如AD。因此，抑制炎症可能会改善AD症状。本研究调查了[具体物质]在链脲佐菌素（STZ）诱导的AD模型中的神经保护作用。在此，我们建立了一种STZ诱导的AD大鼠模型，该模型伴有记忆力丧失和神经炎症的平行恶化。在用ASS（50mg/kg连续14天）治疗结束后，对大鼠进行行为测试（莫里斯水迷宫试验、Y迷宫试验），并评估大鼠海马体的分子参数（DAPK1、Tau5、p-Tau、NF-κB、IL-1β、TNF-α和NLRP3）。我们证明，具有强大抗炎作用的ASS可以减轻神经炎症并预防认知障碍。在水迷宫试验中，与阴性对照组相比，ASS治疗组的平均逃避潜伏期显著增加（<0.05）、在目标象限停留的百分比（<0.05）以及每组大鼠穿过平台的次数（<0.05）。并且ASS可以降低海马组织中Tau蛋白的磷酸化水平（<0.001）和死亡相关蛋白激酶1（DAPK1，<0.001），通过抑制炎症反应改善STZ处理大鼠的认知障碍；分子分析显示促炎标志物如NLRP3、IL-1β、TNF-α和NF-κB显著降低（<0.001）。还发现NF-κB抑制剂SN50具有相同的效果。因此，本研究利用ASS的抗炎作用来预防和治疗AD。本研究突出了ASS在减轻AD认知功能障碍方面的潜在疗效。
