State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, China.
Cell Prolif. 2020 Apr;53(4):e12787. doi: 10.1111/cpr.12787. Epub 2020 Mar 12.
To provide a new research direction for nerve regeneration and strategy for Alzheimer's disease treatment, tetrahedral DNA nanostructures (TDNs)-novel tetrahedral framework nucleic acid molecule nanoparticles (tFNA) that can inhibit the apoptosis of nerve cells are employed in the experiment.
To verify the successful preparation of TDNs, the morphology of TDNs was observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM). The expression of apoptosis-related genes and proteins was investigated by confocal microscope, flow cytometry, PCR and Western blot to detect the impact of TDNs on the Alzheimer's model. And finally, Morris water maze experiment was used to test behavioural changes and Nissl stain was detected to observe the morphology and quantity of neurons in the hippocampus. Immunofluorescence stain was used to observe the Aβ stain, and TUNEL dyeing was utilized to observe neuronal apoptosis.
In vitro and in vivo experiments confirm that TDNs, in a specific concentration range, have no toxic or side effects on nerve cells, can effectively inhibit apoptosis in an Alzheimer's disease cell model and effectively improve memory and learning ability in a rat model of Alzheimer's disease.
These findings suggest that TDNs may be a promising drug for the treatment of Alzheimer's disease.
为神经再生研究提供新方向,为阿尔茨海默病治疗提供策略,实验采用四面体 DNA 纳米结构(TDN)——新型四面体框架核酸分子纳米颗粒(tFNA),可抑制神经细胞凋亡。
通过原子力显微镜(AFM)和透射电子显微镜(TEM)观察 TDN 的形态,验证 TDNs 的成功制备。通过共聚焦显微镜、流式细胞术、PCR 和 Western blot 检测 TDNs 对阿尔茨海默病模型的影响,研究细胞凋亡相关基因和蛋白的表达情况。最后,通过 Morris 水迷宫实验检测行为变化,尼氏染色观察海马神经元的形态和数量,免疫荧光染色观察 Aβ 染色,TUNEL 染色观察神经元凋亡。
体外和体内实验证实,在特定浓度范围内,TDNs 对神经细胞无毒副作用,能有效抑制阿尔茨海默病细胞模型中的细胞凋亡,并能有效改善阿尔茨海默病大鼠模型的记忆和学习能力。
这些发现表明,TDNs 可能是治疗阿尔茨海默病的一种有前途的药物。