Issue 56, 2018

Kinetic barriers to α-synuclein protofilament formation and conversion into mature fibrils

Abstract

Oligomeric and protofibrillar aggregates that are populated along the pathway of amyloid fibril formation appear generally to be more toxic than the mature fibrillar state. In particular, α-synuclein, the protein associated with Parkinson's disease, forms kinetically trapped protofibrils in the presence of lipid vesicles. Here, we show that lipid-induced α-synuclein protofibrils can convert rapidly to mature fibrils at higher temperatures. Furthermore, we find that β-synuclein, generally considered less aggregation prone than α-synuclein, forms protofibrils at higher temperatures. These findings highlight the importance of energy barriers in controlling the de novo formation and conversion of amyloid fibrils.

Graphical abstract: Kinetic barriers to α-synuclein protofilament formation and conversion into mature fibrils

Supplementary files

Article information

Article type
Communication
Submitted
16 Apr 2018
Accepted
12 Jun 2018
First published
28 Jun 2018
This article is Open Access
Creative Commons BY-NC license

Chem. Commun., 2018,54, 7854-7857

Kinetic barriers to α-synuclein protofilament formation and conversion into mature fibrils

J. W. P. Brown, G. Meisl, T. P. J. Knowles, A. K. Buell, C. M. Dobson and C. Galvagnion, Chem. Commun., 2018, 54, 7854 DOI: 10.1039/C8CC03002B

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