A guide to studying protein aggregation

• Published in: The FEBS journal Vol. 290; no. 3; pp. 554 - 583
• Main Authors: Housmans, Joëlle A. J., Wu, Guiqin, Schymkowitz, Joost, Rousseau, Frederic
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.02.2023
• Subjects: Agglomeration; Aggregates; aggregation kinetics; aggregation propensity; aggregation‐prone region; amorphous aggregates; Amyloid; Amyloid - metabolism; Amyloidogenic Proteins; Amyloidosis; biocompatible materials; Biomaterials; Biomedical materials; Biopharmaceuticals; Drug development; fibrils; Food; Food technology; Humans; Peptides; Peptides - metabolism; Protein Aggregates; protein aggregation; Protein Folding; protein homeostasis; Protein interaction; protein stability; Proteins; therapeutics; β‐sheet; β-sheet; aggregation kinetics; aggregation-prone region; protein aggregation; aggregation propensity; protein homeostasis; amorphous aggregates; protein stability; fibrils
• ISSN: 1742-464X; 1742-4658; 1742-4658
• DOI: 10.1111/febs.16312

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. The accumulation of un‐ or misfolded proteins can lead to the formation of amorphous or ordered aggregates. Protein aggregation is often associated with human diseases and unravelling its underlying mechanism is critical for the development of diagnostic methods or treatments. However, investigating protein aggregation is challenging due to its complex and dynamic nature. Here, we summarized some popular methods to study the various aspects and steps involved in protein aggregation.