% 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{Wrdehoff:838456,
author = {Wördehoff, MM and Shaykhalishahi, Hamed and Groß, L. and
Gremer, Lothar and Stoldt, Matthias and Buell, AK and
Willbold, Dieter and Hoyer, Wolfgang},
title = {{O}pposed effects of dityrosine formation in soluble and
aggregated alpha-synuclein on fibril growth},
journal = {Journal of molecular biology},
volume = {429},
issn = {0022-2836},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {FZJ-2017-07059},
pages = {3018-3030},
year = {2017},
abstract = {Parkinson's disease is the second most common
neurodegenerative disease. It is characterized by
aggregation of the protein α-synuclein (α-syn) in Lewy
bodies, mitochondrial dysfunction, and increased oxidative
stress in the substantia nigra. Oxidative stress leads to
several modifications of biomolecules including dityrosine
(DiY) crosslinking in proteins, which has recently been
detected in α-syn in Lewy bodies from Parkinson's disease
patients. Here we report that α-syn is highly susceptible
to ultraviolet-induced DiY formation. We investigated DiY
formation of α-syn and nine tyrosine-to-alanine mutants and
monitored its effect on α-syn fibril formation in vitro.
Ultraviolet irradiation of intrinsically disordered α-syn
generates DiY-modified monomers and dimers, which inhibit
fibril formation of unmodified α-syn by interfering with
fibril elongation. The inhibition depends on both the DiY
group and its integration into α-syn. When preformed α-syn
fibrils are crosslinked by DiY formation, they gain
increased resistance to denaturation. DiY-stabilized α-syn
fibrils retain their high seeding efficiency even after
being exposed to denaturant concentrations that completely
depolymerize non-crosslinked seeds. Oxidative
stress-associated DiY crosslinking of α-syn therefore
entails two opposing effects: (i) inhibition of aggregation
by DiY-modified monomers and dimers, and (ii) stabilization
of fibrillar aggregates against potential degradation
mechanisms, which can lead to promotion of aggregation,
especially in the presence of secondary nucleation.},
cin = {ICS-6},
ddc = {570},
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:28918091},
UT = {WOS:000413614100004},
doi = {10.1016/j.jmb.2017.09.005},
url = {https://juser.fz-juelich.de/record/838456},
}