Amyloid formation as a protein phase transition Michaels, Thomas C.T. Qian, Daoyuan Šarić, Anđela ; https://orcid.org/0000-0002-7854-2139 Vendruscolo, Michele Linse, Sara Knowles, Tuomas P.J. The formation of amyloid fibrils is a general class of protein self-assembly behaviour, which is associated with both functional biology and the development of a number of disorders, such as Alzheimer and Parkinson diseases. In this Review, we discuss how general physical concepts from the study of phase transitions can be used to illuminate the fundamental mechanisms of amyloid self-assembly. We summarize progress in the efforts to describe the essential biophysical features of amyloid self-assembly as a nucleation-and-growth process and discuss how master equation approaches can reveal the key molecular pathways underlying this process, including the role of secondary nucleation. Additionally, we outline how non-classical aspects of aggregate formation involving oligomers or biomolecular condensates have emerged, inspiring developments in understanding, modelling and modulating complex protein assembly pathways. Finally, we consider how these concepts can be applied to kinetics-based drug discovery and therapeutic design to develop treatments for protein aggregation diseases. Springer Nature 2023 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/13237 Michaels TCT, Qian D, Šarić A, Vendruscolo M, Linse S, Knowles TPJ. Amyloid formation as a protein phase transition. <i>Nature Reviews Physics</i>. 2023;5:379–397. doi:<a href="https://doi.org/10.1038/s42254-023-00598-9">10.1038/s42254-023-00598-9</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1038/s42254-023-00598-9 info:eu-repo/semantics/altIdentifier/e-issn/2522-5820 info:eu-repo/semantics/altIdentifier/wos/001017539800001 info:eu-repo/semantics/closedAccess