An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils. / Agerschou, Emil Dandanell; Flagmeier, Patrick; Saridaki, Theodora; Galvagnion, Céline; Komnig, Daniel; Heid, Laetitia; Prasad, Vibha; Shaykhalishahi, Hamed; Willbold, Dieter; Dobson, Christopher M; Voigt, Aaron; Falkenbürger, Björn; Hoyer, Wolfgang; Buell, Alexander K.

In: eLife, Vol. 8, 07.08.2019.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Agerschou, ED, Flagmeier, P, Saridaki, T, Galvagnion, C, Komnig, D, Heid, L, Prasad, V, Shaykhalishahi, H, Willbold, D, Dobson, CM, Voigt, A, Falkenbürger, B, Hoyer, W & Buell, AK 2019, 'An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils', eLife, vol. 8. https://doi.org/10.7554/eLife.46112, https://doi.org/10.7554/eLife.46112

APA

Agerschou, E. D., Flagmeier, P., Saridaki, T., Galvagnion, C., Komnig, D., Heid, L., Prasad, V., Shaykhalishahi, H., Willbold, D., Dobson, C. M., Voigt, A., Falkenbürger, B., Hoyer, W., & Buell, A. K. (2019). An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils. eLife, 8. https://doi.org/10.7554/eLife.46112, https://doi.org/10.7554/eLife.46112

Vancouver

Agerschou ED, Flagmeier P, Saridaki T, Galvagnion C, Komnig D, Heid L et al. An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils. eLife. 2019 Aug 7;8. https://doi.org/10.7554/eLife.46112, https://doi.org/10.7554/eLife.46112

Author

Agerschou, Emil Dandanell ; Flagmeier, Patrick ; Saridaki, Theodora ; Galvagnion, Céline ; Komnig, Daniel ; Heid, Laetitia ; Prasad, Vibha ; Shaykhalishahi, Hamed ; Willbold, Dieter ; Dobson, Christopher M ; Voigt, Aaron ; Falkenbürger, Björn ; Hoyer, Wolfgang ; Buell, Alexander K. / An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils. In: eLife. 2019 ; Vol. 8.

Bibtex

@article{1aaa391b4be2455ba20b2e6f59df20a4,
title = "An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils",
abstract = "Removing or preventing the formation of α-synuclein aggregates is a plausible strategy against Parkinson's disease. To this end we have engineered the β-wrapin AS69 to bind monomeric α-synuclein with high affinity. In cultured cells, AS69 reduced the self-interaction of α-synuclein and the formation of visible α-synuclein aggregates. In flies, AS69 reduced α-synuclein aggregates and the locomotor deficit resulting from α-synuclein expression in neuronal cells. In biophysical experiments in vitro, AS69 highly sub-stoichiometrically inhibited both primary and autocatalytic secondary nucleation processes, even in the presence of a large excess of monomer. We present evidence that the AS69-α-synuclein complex, rather than the free AS69, is the inhibitory species responsible for sub-stoichiometric inhibition of secondary nucleation. These results represent a new paradigm that high affinity monomer binders can lead to strongly sub-stoichiometric inhibition of nucleation processes.",
author = "Agerschou, {Emil Dandanell} and Patrick Flagmeier and Theodora Saridaki and C{\'e}line Galvagnion and Daniel Komnig and Laetitia Heid and Vibha Prasad and Hamed Shaykhalishahi and Dieter Willbold and Dobson, {Christopher M} and Aaron Voigt and Bj{\"o}rn Falkenb{\"u}rger and Wolfgang Hoyer and Buell, {Alexander K}",
note = "{\textcopyright} 2019, Agerschou et al.",
year = "2019",
month = aug,
day = "7",
doi = "10.7554/eLife.46112",
language = "English",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils

AU - Agerschou, Emil Dandanell

AU - Flagmeier, Patrick

AU - Saridaki, Theodora

AU - Galvagnion, Céline

AU - Komnig, Daniel

AU - Heid, Laetitia

AU - Prasad, Vibha

AU - Shaykhalishahi, Hamed

AU - Willbold, Dieter

AU - Dobson, Christopher M

AU - Voigt, Aaron

AU - Falkenbürger, Björn

AU - Hoyer, Wolfgang

AU - Buell, Alexander K

N1 - © 2019, Agerschou et al.

PY - 2019/8/7

Y1 - 2019/8/7

N2 - Removing or preventing the formation of α-synuclein aggregates is a plausible strategy against Parkinson's disease. To this end we have engineered the β-wrapin AS69 to bind monomeric α-synuclein with high affinity. In cultured cells, AS69 reduced the self-interaction of α-synuclein and the formation of visible α-synuclein aggregates. In flies, AS69 reduced α-synuclein aggregates and the locomotor deficit resulting from α-synuclein expression in neuronal cells. In biophysical experiments in vitro, AS69 highly sub-stoichiometrically inhibited both primary and autocatalytic secondary nucleation processes, even in the presence of a large excess of monomer. We present evidence that the AS69-α-synuclein complex, rather than the free AS69, is the inhibitory species responsible for sub-stoichiometric inhibition of secondary nucleation. These results represent a new paradigm that high affinity monomer binders can lead to strongly sub-stoichiometric inhibition of nucleation processes.

AB - Removing or preventing the formation of α-synuclein aggregates is a plausible strategy against Parkinson's disease. To this end we have engineered the β-wrapin AS69 to bind monomeric α-synuclein with high affinity. In cultured cells, AS69 reduced the self-interaction of α-synuclein and the formation of visible α-synuclein aggregates. In flies, AS69 reduced α-synuclein aggregates and the locomotor deficit resulting from α-synuclein expression in neuronal cells. In biophysical experiments in vitro, AS69 highly sub-stoichiometrically inhibited both primary and autocatalytic secondary nucleation processes, even in the presence of a large excess of monomer. We present evidence that the AS69-α-synuclein complex, rather than the free AS69, is the inhibitory species responsible for sub-stoichiometric inhibition of secondary nucleation. These results represent a new paradigm that high affinity monomer binders can lead to strongly sub-stoichiometric inhibition of nucleation processes.

U2 - 10.7554/eLife.46112

DO - 10.7554/eLife.46112

M3 - Journal article

C2 - 31389332

VL - 8

JO - eLife

JF - eLife

SN - 2050-084X

ER -

ID: 225521743