Centre for Prions and Protein Folding Diseases, University of Alberta, 204 Brain and Aging Research Building, 8710-112 St, Edmonton, AB T6G 2M8, Canada.
Neuroscience and Mental Health Institute, University of Alberta, 2-132 Li Ka Shing, Edmonton, AB T6G 2E1, Canada.
Biomolecules. 2020 Jul 20;10(7):1079. doi: 10.3390/biom10071079.
Prion diseases are fatal, transmissible neurodegenerative disorders whose pathogenesis is driven by the misfolding, self-templating and cell-to-cell spread of the prion protein. Other neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease, share some of these prion-like features, with different aggregation-prone proteins. Consequently, researchers have begun to apply prion-specific techniques, like the prion organotypic slice culture assay (POSCA), to these disorders. In this review we explore the ways in which the prion phenomenon has been used in organotypic cultures to study neurodegenerative diseases from the perspective of protein aggregation and spreading, strain propagation, the role of glia in pathogenesis, and efficacy of drug treatments. We also present an overview of the advantages and disadvantages of this culture system compared to in vivo and in vitro models and provide suggestions for new directions.
朊病毒病是致命的、可传播的神经退行性疾病,其发病机制是由朊病毒蛋白的错误折叠、自我模板化和细胞间传播驱动的。其他神经退行性疾病,如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和亨廷顿病,也具有这些类朊病毒特征,其具有不同的易于聚集的蛋白质。因此,研究人员已经开始将朊病毒特异性技术(如朊病毒器官型切片培养测定法(POSCA))应用于这些疾病。在这篇综述中,我们从蛋白质聚集和传播、菌株传播、胶质细胞在发病机制中的作用以及药物治疗效果的角度,探讨了朊病毒现象在器官型培养物中用于研究神经退行性疾病的方法。我们还概述了与体内和体外模型相比,这种培养系统的优缺点,并为新的研究方向提供了建议。