Albert Katrina, Kälvälä Sara, Hakosalo Vili, Syvänen Valtteri, Krupa Patryk, Niskanen Jonna, Peltonen Sanni, Sonninen Tuuli-Maria, Lehtonen Šárka
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland.
Neuroscience Center, University of Helsinki, 00014 Helsinki, Finland.
Biomedicines. 2022 Oct 20;10(10):2649. doi: 10.3390/biomedicines10102649.
Alpha-synuclein's role in diseases termed "synucleinopathies", including Parkinson's disease, has been well-documented. However, after over 25 years of research, we still do not fully understand the alpha-synuclein protein and its role in disease. In vitro cellular models are some of the most powerful tools that researchers have at their disposal to understand protein function. Advantages include good control over experimental conditions, the possibility for high throughput, and fewer ethical issues when compared to animal models or the attainment of human samples. On the flip side, their major disadvantages are their questionable relevance and lack of a "whole-brain" environment when it comes to modeling human diseases, such as is the case of neurodegenerative disorders. Although now, with the advent of pluripotent stem cells and the ability to create minibrains in a dish, this is changing. With this review, we aim to wade through the recent alpha-synuclein literature to discuss how different cell culture setups (immortalized cell lines, primary neurons, human induced pluripotent stem cells (hiPSCs), blood-brain barrier models, and brain organoids) can help us understand aggregation pathology in Parkinson's and other synucleinopathies.
α-突触核蛋白在包括帕金森病在内的被称为“突触核蛋白病”的疾病中的作用已有充分记录。然而，经过25年多的研究，我们仍未完全了解α-突触核蛋白及其在疾病中的作用。体外细胞模型是研究人员用于了解蛋白质功能的一些最强大的工具。其优点包括对实验条件的良好控制、高通量的可能性以及与动物模型或获取人类样本相比更少的伦理问题。另一方面，它们的主要缺点是在模拟人类疾病（如神经退行性疾病）时其相关性存疑且缺乏“全脑”环境。不过现在，随着多能干细胞的出现以及在培养皿中创建微型大脑的能力，这种情况正在改变。通过本综述，我们旨在梳理近期关于α-突触核蛋白的文献，以讨论不同的细胞培养设置（永生化细胞系、原代神经元、人诱导多能干细胞（hiPSC）、血脑屏障模型和脑类器官）如何帮助我们理解帕金森病和其他突触核蛋白病中的聚集病理学。
