Issue 14, 2020

Effects of sedimentation, microgravity, hydrodynamic mixing and air–water interface on α-synuclein amyloid formation

Abstract

The formation of amyloid fibrils is a characterizing feature of a range of protein misfolding diseases, including Parkinson's disease. The propensity of native proteins to form such amyloid fibril, both in vitro and in vivo, is highly sensitive to the surrounding environment, which can alter the aggregation kinetics and fibrillization mechanisms. Here, we investigate systematically the influence of several representative environmental stimuli on α-synuclein aggregation, including hydrodynamic mixing, the presence of an air–water interface and sedimentation. Our results show that hydrodynamic mixing and interfacial effects are critical in promoting several microscopic steps of α-synuclein aggregation and amyloid fibril formation. The presence of an air–water interface under agitation significantly promoted primary nucleation. Secondary processes were facilitated by hydrodynamic mixing, produced by 3D rotation and shaking either in the presence or in the absence of an air–water interface. Effects of sedimentation, as investigated in a microgravity incubator, of α-synuclein lead only to minor changes on the aggregation kinetics rates in comparison to static conditions. These results forward the understanding of α-synuclein fibrillization, paving the way for the development of high-throughput assays for the screening of pharmacological approaches targeting Parkinson's disease.

Graphical abstract: Effects of sedimentation, microgravity, hydrodynamic mixing and air–water interface on α-synuclein amyloid formation

Supplementary files

Article information

Article type
Edge Article
Submitted
15 Janv. 2020
Accepted
06 Marts 2020
First published
10 Marts 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2020,11, 3687-3693

Effects of sedimentation, microgravity, hydrodynamic mixing and air–water interface on α-synuclein amyloid formation

J. Zhou, F. S. Ruggeri, M. R. Zimmermann, G. Meisl, G. Longo, S. K. Sekatskii, T. P. J. Knowles and G. Dietler, Chem. Sci., 2020, 11, 3687 DOI: 10.1039/D0SC00281J

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements