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

James W P Brown; Georg Meisl; Tuomas P J Knowles; Alexander K Buell; Christopher M Dobson; Céline Galvagnion

doi:10.1039/c8cc03002b

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

James W P Brown, Georg Meisl, Tuomas P J Knowles, Alexander K Buell, Christopher M Dobson, Céline Galvagnion

13 Citations (Scopus)

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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.

Original language	English
Journal	Chemical communications (Cambridge, England)
Volume	54
Issue number	56
Pages (from-to)	7854-7857
Number of pages	4
ISSN	1359-7345
DOIs	https://doi.org/10.1039/c8cc03002b
Publication status	Published - 10 Jul 2018
Externally published	Yes

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title = "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.",

author = "Brown, {James W P} and Georg Meisl and Knowles, {Tuomas P J} and Buell, {Alexander K} and Dobson, {Christopher M} and C{\'e}line Galvagnion",

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T1 - Kinetic barriers to α-synuclein protofilament formation and conversion into mature fibrils

AU - Brown, James W P

AU - Meisl, Georg

AU - Knowles, Tuomas P J

AU - Buell, Alexander K

AU - Dobson, Christopher M

AU - Galvagnion, Céline

PY - 2018/7/10

Y1 - 2018/7/10

N2 - 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.

AB - 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.

U2 - 10.1039/c8cc03002b

DO - 10.1039/c8cc03002b

M3 - Journal article

C2 - 29951679

SN - 1359-7345

VL - 54

SP - 7854

EP - 7857

JO - Chemical Communications

JF - Chemical Communications

IS - 56

ER -

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

Abstract

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