Housmans Joëlle A J, Wu Guiqin, Schymkowitz Joost, Rousseau Frederic
Switch Laboratory, VIB Center for Brain and Disease Research, Leuven, Belgium.
Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
FEBS J. 2023 Feb;290(3):554-583. doi: 10.1111/febs.16312. Epub 2021 Dec 13.
Disrupted protein folding or decreased protein stability can lead to the accumulation of (partially) un- or misfolded proteins, which ultimately cause the formation of protein aggregates. Much of the interest in protein aggregation is associated with its involvement in a wide range of human diseases and the challenges it poses for large-scale biopharmaceutical manufacturing and formulation of therapeutic proteins and peptides. On the other hand, protein aggregates can also be functional, as observed in nature, which triggered its use in the development of biomaterials or therapeutics as well as for the improvement of food characteristics. Thus, unmasking the various steps involved in protein aggregation is critical to obtain a better understanding of the underlying mechanism of amyloid formation. This knowledge will allow a more tailored development of diagnostic methods and treatments for amyloid-associated diseases, as well as applications in the fields of new (bio)materials, food technology and therapeutics. However, the complex and dynamic nature of the aggregation process makes the study of protein aggregation challenging. To provide guidance on how to analyse protein aggregation, in this review we summarize the most commonly investigated aspects of protein aggregation with some popular corresponding methods.
蛋白质折叠紊乱或蛋白质稳定性降低会导致（部分）未折叠或错误折叠的蛋白质积累，最终导致蛋白质聚集体的形成。人们对蛋白质聚集的诸多兴趣与其参与多种人类疾病以及给大规模生物制药生产和治疗性蛋白质及肽的制剂带来的挑战有关。另一方面，正如在自然界中观察到的那样，蛋白质聚集体也可以具有功能性，这引发了其在生物材料或治疗方法开发以及改善食品特性方面的应用。因此，揭示蛋白质聚集所涉及的各个步骤对于更好地理解淀粉样蛋白形成的潜在机制至关重要。这些知识将有助于更有针对性地开发针对淀粉样蛋白相关疾病的诊断方法和治疗方法，以及在新型（生物）材料、食品技术和治疗领域的应用。然而，聚集过程的复杂性和动态性使得蛋白质聚集的研究具有挑战性。为了提供有关如何分析蛋白质聚集的指导，在本综述中，我们总结了蛋白质聚集最常研究的方面以及一些常用的相应方法。
