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@ARTICLE{Rsener:877637,
author = {Rösener, Nadine and Gremer, Lothar and Wördehoff, Michael
M. and Kupreichyk, Tatsiana and Etzkorn, Manuel and
Neudecker, Philipp and Hoyer, Wolfgang},
title = {{C}lustering of human prion protein and α-synuclein
oligomers requires the prion protein {N}-terminus},
journal = {Communications biology},
volume = {3},
number = {1},
issn = {2399-3642},
address = {London},
publisher = {Springer Nature},
reportid = {FZJ-2020-02352},
pages = {365},
year = {2020},
abstract = {The interaction of prion protein (PrP) and α-synuclein
(αSyn) oligomers causes synaptic impairment that might
trigger Parkinson’s disease and other synucleinopathies.
Here, we report that αSyn oligomers (αSynO) cluster with
human PrP (huPrP) into micron-sized condensates.
Multivalency of αSyn within oligomers is required for
condensation, since clustering with huPrP is not observed
for monomeric αSyn. The stoichiometry of the
heteroassemblies is well defined with an αSyn:huPrP molar
ratio of about 1:1. The αSynO−huPrP interaction is of
high affinity, signified by slow dissociation. The huPrP
region responsible for condensation of αSynO, residues
95−111 in the intrinsically disordered N-terminus,
corresponds to the region required for αSynO-mediated
cognitive impairment. HuPrP, moreover, achieves
co-clustering of αSynO and Alzheimer’s disease-associated
amyloid-β oligomers, providing a case of a
cross-interaction of two amyloidogenic proteins through an
interlinking intrinsically disordered protein region. The
results suggest that αSynO-mediated condensation of huPrP
is involved in the pathogenesis of synucleinopathies.},
cin = {IBI-7},
ddc = {570},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32647130},
UT = {WOS:000552080500008},
doi = {10.1038/s42003-020-1085-z},
url = {https://juser.fz-juelich.de/record/877637},
}