Amyloid formation as a protein phase transition

article Amyloid formation as a protein phase transition published yes Thomas C.T. Michaels author Daoyuan Qian author Anđela Šarić author bf63d406-f056-11eb-b41d-f263a6566d8b0000-0002-7854-2139 Michele Vendruscolo author Sara Linse author Tuomas P.J. Knowles author AnSa department 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 Nature2023 eng Nature Reviews Physics 2522-5820 00101753980000110.1038/s42254-023-00598-9 5379–397 T. C. T. Michaels, D. Qian, A. Šarić, M. Vendruscolo, S. Linse, and T. P. J. Knowles, “Amyloid formation as a protein phase transition,” Nature Reviews Physics, vol. 5. Springer Nature, pp. 379–397, 2023. Michaels, Thomas C.T., Daoyuan Qian, Anđela Šarić, Michele Vendruscolo, Sara Linse, and Tuomas P.J. Knowles. “Amyloid Formation as a Protein Phase Transition.” Nature Reviews Physics. Springer Nature, 2023. <a href="https://doi.org/10.1038/s42254-023-00598-9">https://doi.org/10.1038/s42254-023-00598-9</a>. Michaels, T. C. T., Qian, D., Šarić, A., Vendruscolo, M., Linse, S., & Knowles, T. P. J. (2023). Amyloid formation as a protein phase transition. Nature Reviews Physics. Springer Nature. <a href="https://doi.org/10.1038/s42254-023-00598-9">https://doi.org/10.1038/s42254-023-00598-9</a> Michaels TCT, Qian D, Šarić A, Vendruscolo M, Linse S, Knowles TPJ. 2023. Amyloid formation as a protein phase transition. Nature Reviews Physics. 5, 379–397. T.C.T. Michaels, D. Qian, A. Šarić, M. Vendruscolo, S. Linse, T.P.J. Knowles, Nature Reviews Physics 5 (2023) 379–397. Michaels, Thomas C. T., et al. “Amyloid Formation as a Protein Phase Transition.” Nature Reviews Physics, vol. 5, Springer Nature, 2023, pp. 379–397, doi:<a href="https://doi.org/10.1038/s42254-023-00598-9">10.1038/s42254-023-00598-9</a>. Michaels TCT, Qian D, Šarić A, Vendruscolo M, Linse S, Knowles TPJ. Amyloid formation as a protein phase transition. Nature Reviews Physics. 2023;5:379–397. doi:<a href="https://doi.org/10.1038/s42254-023-00598-9">10.1038/s42254-023-00598-9</a> 132372023-07-16T22:01:12Z2023-08-02T06:28:38Z