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帕金森病建模:诱导多能干细胞助力深入了解人类病理学

Modelling Parkinson's Disease: iPSCs towards Better Understanding of Human Pathology.

作者信息

Avazzadeh Sahar, Baena Jara Maria, Keighron Cameron, Feller-Sanchez Yajaira, Quinlan Leo R

机构信息

Physiology and CÚRAM SFI Centre for Research in Medical Devices, School of Medicine, National University of Ireland (NUI), H91 TK33 Galway, Ireland.

出版信息

Brain Sci. 2021 Mar 14;11(3):373. doi: 10.3390/brainsci11030373.

Abstract

Parkinson's Disease (PD) is a chronic neurodegenerative disorder characterized by motor and non-motor symptoms, among which are bradykinesia, rigidity, tremor as well as mental symptoms such as dementia. The underlying cause of Parkinson disease is degeneration of dopaminergic neurons. It has been challenging to develop an efficient animal model to accurately represent the complex phenotypes found with PD. However, it has become possible to recapitulate the myriad of phenotypes underlying the PD pathology by using human induced pluripotent stem cell (iPSC) technology. Patient-specific iPSC-derived dopaminergic neurons are available and present an opportunity to study many aspects of the PD phenotypes in a dish. In this review, we report the available data on iPSC-derived neurons derived from PD patients with identified gene mutations. Specifically, we will report on the key phenotypes of the generated iPSC-derived neurons from PD patients with different genetic background. Furthermore, we discuss the relationship these cellular phenotypes have to PD pathology and future challenges and prospects for iPSC modelling and understanding of the pathogenesis of PD.

摘要

帕金森病(PD)是一种慢性神经退行性疾病,其特征为运动和非运动症状,包括运动迟缓、僵硬、震颤以及痴呆等精神症状。帕金森病的根本原因是多巴胺能神经元的变性。开发一种能准确呈现帕金森病复杂表型的有效动物模型一直具有挑战性。然而,通过使用人类诱导多能干细胞(iPSC)技术,再现帕金森病病理背后的众多表型已成为可能。患者特异性的iPSC衍生多巴胺能神经元已可获得,这为在培养皿中研究帕金森病表型的诸多方面提供了机会。在本综述中,我们报告了来自具有已鉴定基因突变的帕金森病患者的iPSC衍生神经元的现有数据。具体而言,我们将报告来自不同遗传背景的帕金森病患者所产生的iPSC衍生神经元的关键表型。此外,我们讨论了这些细胞表型与帕金森病病理的关系以及iPSC建模和理解帕金森病发病机制的未来挑战与前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b95/8000082/307c50b144f4/brainsci-11-00373-g001.jpg

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