Amyloid formation as a protein phase transition
(2023) In Nature Reviews Physics 5(7). p.379-397- Abstract
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... (More)
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.
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- author
- Michaels, Thomas C.T. ; Qian, Daoyuan ; Šarić, Anđela ; Vendruscolo, Michele ; Linse, Sara LU and Knowles, Tuomas P.J.
- organization
- publishing date
- 2023-07
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Reviews Physics
- volume
- 5
- issue
- 7
- pages
- 19 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85163364439
- ISSN
- 2522-5820
- DOI
- 10.1038/s42254-023-00598-9
- language
- English
- LU publication?
- yes
- id
- ff98336f-1619-417c-8aeb-d65b0516bebf
- date added to LUP
- 2023-11-07 15:37:53
- date last changed
- 2023-11-22 03:54:58
@article{ff98336f-1619-417c-8aeb-d65b0516bebf,
abstract = {{<p>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.</p>}},
author = {{Michaels, Thomas C.T. and Qian, Daoyuan and Šarić, Anđela and Vendruscolo, Michele and Linse, Sara and Knowles, Tuomas P.J.}},
issn = {{2522-5820}},
language = {{eng}},
number = {{7}},
pages = {{379--397}},
publisher = {{Nature Publishing Group}},
series = {{Nature Reviews Physics}},
title = {{Amyloid formation as a protein phase transition}},
url = {{http://dx.doi.org/10.1038/s42254-023-00598-9}},
doi = {{10.1038/s42254-023-00598-9}},
volume = {{5}},
year = {{2023}},
}