State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Junhui Biotechnology Co. Ltd., No. 10 Furong Avenue 2, Wenjiang District, Chengdu 611100, China.
Biomed Pharmacother. 2024 Nov;180:117540. doi: 10.1016/j.biopha.2024.117540. Epub 2024 Oct 13.
To investigate the therapeutic effects and mechanisms of Semaglutide in Alzheimer's disease (AD), and identify its potential targets.
We systematically evaluated the effect of Semaglutide on Alzheimer's disease (AD), using both mice and human organoid models.
Behavioral analyses on APP/PS1 mice demonstrated that Semaglutide improved the cognitive capabilities, particularly in the learning and memory domains. Biochemical investigations further highlighted its role in reducing amyloid plaque deposition and down-regulating the expression of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) expression in the mouse brain tissues. Meanwhile, oxytocin (OXT) was up-regulated after Semaglutide treatment. Subsequent studies using human AD-brain organoids (BOs) models revealed that, upon Semaglutide treatment, these AD-BO models also exhibited reduced levels of amyloid-beta (Aβ), phosphorylated Tau (p-Tau) and GFAP expression as well as increased OXT level.
Semaglutide can ameliorate Alzheimer's disease in pre-clinical models, suggesting the promising therapeutic potential in AD patients.
探讨司美格鲁肽在阿尔茨海默病（AD）中的治疗作用和机制，并确定其潜在靶点。
我们采用 APP/PS1 小鼠和人类类器官模型，系统评估了司美格鲁肽对 AD 的影响。
APP/PS1 小鼠的行为分析表明，司美格鲁肽改善了认知能力，特别是在学习和记忆领域。生化研究进一步表明，它可减少淀粉样斑块沉积，并下调小鼠脑组织中神经胶质纤维酸性蛋白（GFAP）和钙结合蛋白 1（Iba1）的表达。同时，司美格鲁肽治疗后可上调催产素（OXT）。随后使用人 AD-脑类器官（BO）模型的研究表明，司美格鲁肽治疗后，这些 AD-BO 模型的淀粉样β（Aβ）、磷酸化 Tau（p-Tau）和 GFAP 表达降低，OXT 水平升高。
司美格鲁肽可改善临床前模型中的阿尔茨海默病，表明其在 AD 患者中有潜在的治疗作用。
