Semaglutide ameliorates Alzheimer's disease and restores oxytocin in APP/PS1 mice and human brain organoid models.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-13 DOI:10.1016/j.biopha.2024.117540

Yinbing Zhang, Cheng Tang, Yao He, Yingqian Zhang, Qinxi Li, Ting Zhang, Bangcheng Zhao, Aiping Tong, Qixing Zhong, Zhihui Zhong

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Abstract

Aims: To investigate the therapeutic effects and mechanisms of Semaglutide in Alzheimer's disease (AD), and identify its potential targets.

Methods: We systematically evaluated the effect of Semaglutide on Alzheimer's disease (AD), using both mice and human organoid models.

Results: 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.

Conclusions: Semaglutide can ameliorate Alzheimer's disease in pre-clinical models, suggesting the promising therapeutic potential in AD patients.

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塞马鲁肽在APP/PS1小鼠和人脑类器官模型中改善阿尔茨海默病并恢复催产素。

目的：研究塞马鲁肽对阿尔茨海默病（AD）的治疗效果和机制，并确定其潜在靶点：方法：我们利用小鼠和人类类器官模型系统评估了塞马鲁肽对阿尔茨海默病（AD）的影响：结果：对APP/PS1小鼠的行为分析表明，塞马鲁肽改善了小鼠的认知能力，尤其是在学习和记忆领域。生化研究进一步强调了塞马鲁肽在减少淀粉样斑块沉积、下调小鼠脑组织中胶质纤维酸性蛋白（GFAP）和电离钙结合适配分子1（Iba1）表达方面的作用。同时，塞马鲁肽治疗后，催产素（OXT）的表达上调。随后利用人体AD-脑器官组织（BOs）模型进行的研究发现，在塞马鲁肽治疗后，这些AD-BO模型也显示出淀粉样β（Aβ）、磷酸化Tau（p-Tau）和GFAP表达水平的降低以及OXT水平的升高：结论：塞马鲁肽能在临床前模型中改善阿尔茨海默病，这表明它对AD患者具有良好的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

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