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@ARTICLE{Braczynski:906834,
author = {Braczynski, Anne K. and Sevenich, Marc and Gering, Ian and
Kupreichyk, Tatsiana and Agerschou, Emil D. and Kronimus,
Yannick and Habib, Pardes and Stoldt, Matthias and Willbold,
Dieter and Schulz, Jörg B. and Bach, Jan-Philipp and
Falkenburger, Björn H. and Hoyer, Wolfgang},
title = {{A}lpha-{S}ynuclein-{S}pecific {N}aturally {O}ccurring
{A}ntibodies {I}nhibit {A}ggregation {I}n {V}itro and {I}n
{V}ivo},
journal = {Biomolecules},
volume = {12},
number = {3},
issn = {2218-273X},
address = {Basel},
publisher = {MDPI},
reportid = {FZJ-2022-01728},
pages = {469 -},
year = {2022},
abstract = {Parkinson’s disease (PD) is associated with motor and
non-motor symptoms and characterized by aggregates of
alpha-synuclein (αSyn). Naturally occurring antibodies
(nAbs) are part of the innate immune system, produced
without prior contact to their specific antigen, and
polyreactive. The abundance of nAbs against αSyn is altered
in patients with PD. In this work, we biophysically
characterized nAbs against αSyn (nAbs-αSyn) and determined
their biological effects. nAbs-αSyn were isolated from
commercial intravenous immunoglobulins using column affinity
purification. Biophysical properties were characterized
using a battery of established in vitro assays. Biological
effects were characterized in HEK293T cells transiently
transfected with fluorescently tagged αSyn. Specific
binding of nAbs-αSyn to monomeric αSyn was demonstrated by
Dot blot, ELISA, and Surface Plasmon Resonance. nAbs-αSyn
did not affect viability of HEK293T cells as reported by
Cell Titer Blue and LDH Assays. nAbs-αSyn inhibited
fibrillation of αSyn reported by the Thioflavin T
aggregation assay. Altered fibril formation was confirmed
with atomic force microscopy. In cells transfected with
EGFP-tagged αSyn we observed reduced formation of
aggresomes, perinuclear accumulations of αSyn aggregates.
The results demonstrate that serum of healthy individuals
contains nAbs that specifically bind αSyn and inhibit
aggregation of αSyn in vitro. The addition of nAbs-αSyn to
cultured cells affects intracellular αSyn aggregates. These
findings help understanding the role of the innate immune
systems for the pathogenesis of PD and suggest that systemic
αSyn binding agents could potentially affect neuronal αSyn
pathology.},
cin = {IBI-7 / INM-11},
ddc = {570},
cid = {I:(DE-Juel1)IBI-7-20200312 / I:(DE-Juel1)INM-11-20170113},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35327661},
UT = {WOS:000775905700001},
doi = {10.3390/biom12030469},
url = {https://juser.fz-juelich.de/record/906834},
}