Department of Physiology and Pharmacology, Pasteur Instittableute of Iran, Tehran, Iran.
Stem Cell and Regenerative Medicine Center, Tehran University of Medical Sciences, Tehran, Iran.
J Cell Physiol. 2020 Dec;235(12):9166-9184. doi: 10.1002/jcp.29800. Epub 2020 May 21.
Based on investigations, there exist tight correlations between neurodegenerative diseases' incidence and progression and aberrant protein aggregreferates in nervous tissue. However, the pathology of these diseases is not well known, leading to an inability to find an appropriate therapeutic approach to delay occurrence or slow many neurodegenerative diseases' development. The accessibility of induced pluripotent stem cells (iPSCs) in mimicking the phenotypes of various late-onset neurodegenerative diseases presents a novel strategy for in vitro disease modeling. The iPSCs provide a valuable and well-identified resource to clarify neurodegenerative disease mechanisms, as well as prepare a promising human stem cell platform for drug screening. Undoubtedly, neurodegenerative disease modeling using iPSCs has established innovative opportunities for both mechanistic types of research and recognition of novel disease treatments. Most important, the iPSCs have been considered as a novel autologous cell origin for cell-based therapy of neurodegenerative diseases following differentiation to varied types of neural lineage cells (e.g. GABAergic neurons, dopamine neurons, cortical neurons, and motor neurons). In this review, we summarize iPSC-based disease modeling in neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease. Moreover, we discuss the efficacy of cell-replacement therapies for neurodegenerative disease.
基于研究，神经退行性疾病的发病率和进展与神经组织中异常的蛋白质聚集物之间存在紧密的相关性。然而，这些疾病的病理学尚不清楚，导致无法找到适当的治疗方法来延迟发生或减缓许多神经退行性疾病的发展。诱导多能干细胞（iPSC）在模拟各种迟发性神经退行性疾病表型方面的可及性为体外疾病建模提供了一种新策略。iPSC 为阐明神经退行性疾病机制提供了宝贵且明确的资源，并为药物筛选准备了有前途的人类干细胞平台。毫无疑问，使用 iPSC 进行神经退行性疾病建模为机制研究和新型疾病治疗方法的识别开辟了创新机会。最重要的是，iPSC 被认为是神经退行性疾病基于细胞的治疗的新型自体细胞起源，可以分化为各种神经谱系细胞（例如 GABA 能神经元、多巴胺神经元、皮层神经元和运动神经元）。在这篇综述中，我们总结了基于 iPSC 的神经退行性疾病模型，包括阿尔茨海默病、肌萎缩侧索硬化症、帕金森病和亨廷顿病。此外，我们还讨论了细胞替代疗法治疗神经退行性疾病的效果。
