Liu Chang, Wang Xiaoqing, Xu Wei, Yu Songli, Zhang Yueru, Xu Qiming, Tan Xiangshi
Department of Chemistry, Fudan University, Shanghai 200433, China.
School of Advanced Materials Engineering, Jiaxing Nanhu University, Jiaxing 314000, China.
Pharmaceuticals (Basel). 2025 Jun 29;18(7):977. doi: 10.3390/ph18070977.
: To study the efficacy and pharmacological mechanism of the dual-target liposome complex AD808 in the treatment of Alzheimer's disease. : Using APP/PS1 mouse models, the therapeutic efficacy and pharmacological mechanism of AD808 on Alzheimer's disease were studied through water maze tests, brain tissue staining, immunofluorescence, and ELISA for inflammatory and neurotrophic factors. : AD808 exhibited significant pharmacodynamic effects in improving behavioral and cognitive abilities (70% reduction in escape latency) and repairing damaged nerve cells (90% reduction in Aβ plaque) in Alzheimer's disease mice. The efficacy of the liposome complex AD808 was significantly better than that of ST707 or gh625-ZnMT3 alone. AD808 significantly reduced brain inflammation (57.3% and 61.5% reductions in TNF-α and IL-1β, respectively) in AD (Alzheimer's disease) mouse models and promoted the upregulation of neurotrophic factors and nerve growth factors (142.8% increase in BDNF, 275.9% in GDNF, and 111.3% in NGF-1) in brain homogenates. By activating the PI3K/AKT signaling pathway in brain microglia, AD808 upregulated TREM2 protein expression and removed Aβ amyloid plaques in the brain. Additionally, it promoted the transition of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, regulated the M1/M2 balance, released anti-inflammatory and neurotrophic factors, reduced chronic inflammation, and enhanced neurological repair. Based on these results, the potential pharmacological mechanism of AD808 against Alzheimer's disease was proposed. : As a dual-target liposome complex, AD808 has shown promising therapeutic potential in the treatment of Alzheimer's disease, providing a new strategy for innovative drug development.
研究双靶点脂质体复合物AD808治疗阿尔茨海默病的疗效及药理机制。
采用APP/PS1小鼠模型，通过水迷宫试验、脑组织染色、免疫荧光以及炎症和神经营养因子的酶联免疫吸附测定（ELISA），研究AD808对阿尔茨海默病的治疗效果和药理机制。
AD808在改善阿尔茨海默病小鼠的行为和认知能力（逃避潜伏期缩短70%）以及修复受损神经细胞（Aβ斑块减少90%）方面表现出显著的药效学作用。脂质体复合物AD808的疗效明显优于单独使用的ST707或gh625-ZnMT3。AD808显著降低了AD（阿尔茨海默病）小鼠模型中的脑内炎症（肿瘤坏死因子-α和白细胞介素-1β分别降低57.3%和61.5%），并促进了脑匀浆中神经营养因子和神经生长因子的上调（脑源性神经营养因子增加142.8%，胶质细胞源性神经营养因子增加275.9%，神经生长因子-1增加111.3%）。通过激活脑小胶质细胞中的PI3K/AKT信号通路，AD808上调了触发受体表达2（TREM2）蛋白的表达，并清除了脑内的Aβ淀粉样斑块。此外，它促进小胶质细胞从促炎M1表型向抗炎M2表型转变，调节M1/M2平衡，释放抗炎和神经营养因子，减轻慢性炎症，并增强神经修复。基于这些结果，提出了AD808对抗阿尔茨海默病的潜在药理机制。
作为一种双靶点脂质体复合物，AD808在阿尔茨海默病治疗中显示出有前景的治疗潜力，为创新药物开发提供了新策略。
