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@ARTICLE{Pesch:1025963,
author = {Pesch, Verena and Flores-Fernandez, José Miguel and
Reithofer, Sara and Ma, Liang and Özdüzenciler, Pelin and
Busch, Yannick and Sriraman, Aishwarya and Wang, YongLiang
and Amidian, Sara and Kroepel, Chiara V M and Müller, Laura
and Lien, Yi and Rudtke, Olivia and Frieg, Benedikt and
Schröder, Gunnar F and Wille, Holger and Tamgüney,
Gültekin},
title = {{V}accination with structurally adapted fungal protein
fibrils induces immunity to {P}arkinson’s disease},
journal = {Brain},
volume = {147},
number = {5},
issn = {0006-8950},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {FZJ-2024-03241},
pages = {1644-1652},
year = {2024},
abstract = {The pathological misfolding and aggregation of soluble
α-synuclein into toxic oligomers and insoluble amyloid
fibrils causes Parkinson's disease, a progressive
age-related neurodegenerative disease for which there is no
cure. HET-s is a soluble fungal protein that can form
assembled amyloid fibrils in its prion state. We engineered
HET-s(218-298) to form four different fibrillar vaccine
candidates, each displaying a specific conformational
epitope present on the surface of α-synuclein fibrils.
Vaccination with these four vaccine candidates prolonged the
survival of immunized TgM83+/- mice challenged with
α-synuclein fibrils by $8\%$ when injected into the brain
to model brain-first Parkinson's disease or by $21\%$ and
$22\%$ when injected into the peritoneum or gut wall,
respectively, to model body-first Parkinson's disease.
Antibodies from fully immunized mice recognized α-synuclein
fibrils and brain homogenates from patients with Parkinson's
disease, dementia with Lewy bodies and multiple system
atrophy. Conformation-specific vaccines that mimic epitopes
present only on the surface of pathological fibrils but not
on soluble monomers, hold great promise for protection
against Parkinson's disease, related synucleinopathies and
other amyloidogenic protein misfolding disorders.},
cin = {IBI-7},
ddc = {610},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {38428032},
UT = {WOS:001206420100001},
doi = {10.1093/brain/awae061},
url = {https://juser.fz-juelich.de/record/1025963},
}