miRNA-221 可挽救帕金森病小鼠模型中多巴胺能神经元的丢失。
microRNA-221 rescues the loss of dopaminergic neurons in a mouse model of Parkinson's disease.
机构信息
Department 7 of Neurology, Cangzhou Central Hospital, Cangzhou, Hebei, China.
College of Mechanical and Electrical Engineering, Cangzhou Normal University, Cangzhou, Hebei, China.
出版信息
Brain Behav. 2023 Mar;13(3):e2921. doi: 10.1002/brb3.2921. Epub 2023 Feb 16.
BACKGROUND
Parkinson's disease (PD) is one of the most common systemic neurodegenerative diseases and is related to the loss of dopaminergic neurons in the substantia nigra. Several studies verified that microRNA (miRNAs) targeting the Bim/Bax/caspase-3 signaling axis is involved in the apoptosis of dopaminergic neurons in substantia nigra. In this study, we aimed to explore the role of miR-221 in PD.
METHODS
To examine the function of miR-221 in vivo, we used a well-established 6-OHDA-induced PD mouse model. Then we conducted adenovirus-mediated miR-221 overexpression in the PD mice.
RESULTS
Our results showed that miR-221 overexpression improved motor behavior of the PD mice. We demonstrated that overexpression of miR-221 reduced the loss of dopaminergic neurons in the substantia nigra striatum by promoting their antioxidative and antiapoptosis capacities. Mechanistically, miR-221 targets Bim, thus inhibiting Bim and Bax caspase-3 mediated apoptosis signaling pathways.
CONCLUSION
Our findings suggest miR-221 participates in the pathological process of PD and might be a potential drug target and provide new insight into PD treatment.
背景
帕金森病（PD）是最常见的系统性神经退行性疾病之一，与黑质中多巴胺能神经元的丧失有关。几项研究证实，针对 Bim/Bax/caspase-3 信号轴的 microRNA（miRNAs）参与了黑质中多巴胺能神经元的凋亡。在这项研究中，我们旨在探讨 miR-221 在 PD 中的作用。
方法
为了研究 miR-221 在体内的功能，我们使用了已建立的 6-OHDA 诱导的 PD 小鼠模型。然后，我们在 PD 小鼠中进行了腺病毒介导的 miR-221 过表达。
结果
我们的结果表明，miR-221 的过表达改善了 PD 小鼠的运动行为。我们证明，通过促进其抗氧化和抗凋亡能力，miR-221 的过表达减少了黑质纹状体中多巴胺能神经元的丢失。机制上，miR-221 靶向 Bim，从而抑制 Bim 和 Bax caspase-3 介导的凋亡信号通路。
结论
我们的发现表明 miR-221 参与了 PD 的病理过程，可能是一个潜在的药物靶点，并为 PD 的治疗提供了新的见解。
Zotero 插件