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基于诱导多能干细胞的神经退行性疾病建模的当前进展

Current Development of iPSC-Based Modeling in Neurodegenerative Diseases.

作者信息

Guo Xiangge, Wang Xumeng, Wang Jiaxuan, Ma Min, Ren Qian

机构信息

Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, China.

Human Brain Bank, Hebei Medical University, Shijiazhuang 050017, China.

出版信息

Int J Mol Sci. 2025 Apr 16;26(8):3774. doi: 10.3390/ijms26083774.

Abstract

Over the past two decades, significant advancements have been made in the induced pluripotent stem cell (iPSC) technology. These developments have enabled the broader application of iPSCs in neuroscience, improved our understanding of disease pathogenesis, and advanced the investigation of therapeutic targets and methods. Specifically, optimizations in reprogramming protocols, coupled with improved neuronal differentiation and maturation techniques, have greatly facilitated the generation of iPSC-derived neural cells. The integration of the cerebral organoid technology and CRISPR/Cas9 genome editing has further propelled the application of iPSCs in neurodegenerative diseases to a new stage. Patient-derived or CRISPR-edited cerebral neurons and organoids now serve as ideal disease models, contributing to our understanding of disease pathophysiology and identifying novel therapeutic targets and candidates. In this review, we examine the development of iPSC-based models in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease.

摘要

在过去二十年中,诱导多能干细胞(iPSC)技术取得了重大进展。这些进展使iPSC在神经科学中的应用更加广泛,增进了我们对疾病发病机制的理解,并推动了治疗靶点和方法的研究。具体而言,重编程方案的优化,以及改进的神经元分化和成熟技术,极大地促进了iPSC衍生神经细胞的生成。脑类器官技术与CRISPR/Cas9基因组编辑的整合,进一步将iPSC在神经退行性疾病中的应用推进到一个新阶段。患者来源的或经CRISPR编辑的脑神经元和类器官现在成为理想的疾病模型,有助于我们理解疾病病理生理学,并识别新的治疗靶点和候选药物。在这篇综述中,我们考察了基于iPSC的模型在神经退行性疾病中的发展,包括阿尔茨海默病、帕金森病和亨廷顿病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4010/12027653/cb0a0026083b/ijms-26-03774-g001.jpg

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