Zhang Jing, Yang Xuehan, Wang Sushan, Dong Jianhua, Zhang Meishuang, Zhang Ming, Chen Li
Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.
School of Nursing, Jilin University, Changchun, 130021, China.
Mater Today Bio. 2024 Nov 16;29:101347. doi: 10.1016/j.mtbio.2024.101347. eCollection 2024 Dec.
Alzheimer's disease (AD) is characterized by progressive cognitive decline due to neuronal damage and impaired neurogenesis. Preserving neuronal integrity and stimulating neurogenesis are promising therapeutic strategies to combat AD-related cognitive dysfunction. In this study, we synthesized metformin carbon dots (CMCDs) using a hydrothermal method with metformin hydrochloride and citric acid as precursors. Notably, we found that CMCDs were significantly more effective than metformin in promoting the differentiation of neural stem cells (NSCs) into functional neurons under amyloid-beta (Aβ) conditions. Moreover, CMCDs fostered NSCs proliferation, enhanced neurogenesis, reduced Aβ deposition, and inhibited glial cell activation. We also examined neuronal structure by assessing Map2/NF-H/PSD95/SYN expression in the hippocampus, finding that CMCDs robustly strengthened neuronal structure. These results suggest that CMCDs can cognitive dysfunction in AD and promote the proliferation and neurogenesis of NSCs, as well as ameliorate neuronal injury. Hence, CMCDs emerge as promising candidates for AD therapy, demonstrating superior efficacy compared to metformin alone, and offering novel insights into small molecule drug interventions for AD.
阿尔茨海默病(AD)的特征是由于神经元损伤和神经发生受损导致进行性认知衰退。保持神经元完整性和刺激神经发生是对抗AD相关认知功能障碍的有前景的治疗策略。在本研究中,我们以盐酸二甲双胍和柠檬酸为前体,采用水热法合成了二甲双胍碳点(CMCDs)。值得注意的是,我们发现CMCDs在β-淀粉样蛋白(Aβ)条件下促进神经干细胞(NSCs)向功能性神经元分化方面比二甲双胍显著更有效。此外,CMCDs促进NSCs增殖,增强神经发生,减少Aβ沉积,并抑制胶质细胞活化。我们还通过评估海马体中Map2/NF-H/PSD95/SYN的表达来检查神经元结构,发现CMCDs有力地加强了神经元结构。这些结果表明,CMCDs可以改善AD中的认知功能障碍,促进NSCs的增殖和神经发生,并减轻神经元损伤。因此,CMCDs成为AD治疗的有前景的候选物,与单独使用二甲双胍相比显示出卓越的疗效,并为AD的小分子药物干预提供了新的见解。