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

TY - JOUR

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 -