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@ARTICLE{Agerschou:140939,
author = {Agerschou, Emil Dandanell and Flagmeier, Patrick and
Saridaki, Theodora and Galvagnion, Céline and Komnig,
Daniel and Heid, Laetitia and Prasad, Vibha and
Shaykhalishahi, Hamed and Willbold, Dieter and Dobson,
Christopher M and Voigt, Aaron and Falkenburger, Bjoern and
Hoyer, Wolfgang and Buell, Alexander K},
title = {{A}n engineered monomer binding-protein for α-synuclein
efficiently inhibits the proliferation of amyloid fibrils.},
journal = {eLife},
volume = {8},
issn = {2050-084X},
address = {Cambridge},
publisher = {eLife Sciences Publications},
reportid = {DZNE-2020-07261},
pages = {e46112},
year = {2019},
abstract = {Removing or preventing the formation of [Formula: see
text]-synuclein aggregates is a plausible strategy against
Parkinson's disease. To this end, we have engineered the
[Formula: see text]-wrapin AS69 to bind monomeric [Formula:
see text]-synuclein with high affinity. In cultured cells,
AS69 reduced the self-interaction of [Formula: see
text]-synuclein and formation of visible [Formula: see
text]-synuclein aggregates. In flies, AS69 reduced [Formula:
see text]-synuclein aggregates and the locomotor deficit
resulting from [Formula: see text]-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-[Formula: see text]-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.},
keywords = {Amyloid: antagonists $\&$ inhibitors / HEK293 Cells /
Humans / Protein Aggregation, Pathological / Protein
Multimerization: drug effects / Recombinant Proteins:
genetics / Recombinant Proteins: metabolism /
alpha-Synuclein: metabolism},
cin = {AG Di Monte},
ddc = {600},
cid = {I:(DE-2719)1013008},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31389332},
pmc = {pmc:PMC6721797},
doi = {10.7554/eLife.46112},
url = {https://pub.dzne.de/record/140939},
}