Single-molecule observation of self-propagating amyloid fibrils.

Takahiro Watanabe-Nakayama, Kenjiro Ono

Microscopy (Oxford, England) 2022 Jun 06

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The assembly of misfolded proteins into amyloid fibrils is associated with amyloidosis, including neurodegenerative diseases such as Alzheimer's, Parkinson's and prion diseases. The self-propagation of amyloid fibrils is widely observed in the aggregation pathways of numerous amyloidogenic proteins. This propensity with plasticity in primary nucleation allows amyloid fibril polymorphism, which is correlated with the pathology/phenotypes of patients. Because the interference with the nucleation and replication processes of amyloid fibrils can alter the amyloid structure and the outcome of the disease, these processes can be a target for developing clinical drugs. Single-molecule observations of amyloid fibril replication can be an experimental system to provide the kinetic parameters for simulation studies and confirm the effect of clinical drugs. Here, we review the single-molecule observation of the amyloid fibril replication process using fluorescence microscopy and time-lapse atomic force microscopy, including high-speed atomic force microscopy. We discussed the amyloid fibril replication process and combined single-molecule observation results with molecular dynamics simulations. © The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Takahiro Watanabe-Nakayama, Kenjiro Ono. Single-molecule observation of self-propagating amyloid fibrils. Microscopy (Oxford, England). 2022 Jun 06;71(3):133-141