Department of Chemsitry, University of Cambridge, CB2 1EW, United Kingdom.
Department of Chemsitry, University of Cambridge, CB2 1EW, United Kingdom; Cavendish Laboratory, University of Cambridge, Cambridge, CB3 0HE, United Kingdom.
Curr Opin Neurobiol. 2020 Apr;61:58-64. doi: 10.1016/j.conb.2020.01.010. Epub 2020 Feb 21.
The formation of aggregates from a range of normally soluble peptides and proteins is the hallmark of several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. Certain such aggregates possess the ability to replicate and spread pathology, within tissues and in some case also between organisms. An understanding of which processes govern the overall rate of aggregate formation is thus of key interest. Here, we discuss the fundamental molecular processes of protein aggregation, review how their rates can be determined by kinetic measurements in the test-tube, and explore the mechanistic similarities and differences to animal models and human disease. We conclude that a quantitative mathematical model for aggregate replication and spreading in vivo requires additional information but would provide a theoretical framework to understand results from different experiments and how they connect to human disease.
一系列原本可溶的肽和蛋白质形成聚集体是几种神经退行性疾病（包括帕金森病和阿尔茨海默病）的特征。某些此类聚集体具有在组织内复制和传播病理学的能力，在某些情况下也可以在生物体之间传播。因此，了解哪些过程控制着聚集体形成的总体速率是非常重要的。在这里，我们讨论了蛋白质聚集的基本分子过程，回顾了如何通过试管中的动力学测量来确定它们的速率，并探讨了与动物模型和人类疾病的机制相似性和差异性。我们得出结论，一个用于体内聚集体复制和传播的定量数学模型需要额外的信息，但它将提供一个理论框架，以理解来自不同实验的结果以及它们如何与人类疾病相关。
