% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Agerschou:862747,
author = {Agerschou, Emil D. and Saridaki, Theodora and Flagmeier,
Patrick and Galvagnion, Céline and Komnig, Daniel and
Nagpal, Akansha and Gasterich, Natalie and Heid, Laetitia
and Prasad, Vibha and Shaykhalishahi, Hamed and Voigt, Aaron
and Willbold, Dieter and Dobson, Christopher M. and
Falkenburger, Björn H. 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 = {FZJ-2019-02989},
pages = {e46112},
year = {2019},
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 occurrence of α-synuclein
oligomers and 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 a mouse model based on the intracerebral injection
of pre-formed α-synuclein seed fibrills (PFFs), AS69
co-injection reduced the density of dystrophic neurites
observed three months later. In biophysical experiments in
vitro, AS69 highly sub-stoichiometrically inhibited
auto-catalytic 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. These results represent a new
paradigm that high affinity monomer binders can be strongly
sub-stoichiometric inhibitors of nucleation processes.},
cin = {ICS-6},
ddc = {600},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31389332},
UT = {WOS:000484182000001},
doi = {10.7554/eLife.46112},
url = {https://juser.fz-juelich.de/record/862747},
}