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@ARTICLE{Hfs:1030668,
author = {Höfs, Lennart and Geißler-Lösch, David and Wunderlich,
Kristof M. and Szegö, Eva M. and Van den Haute, Chris and
Baekelandt, Veerle and Hoyer, Wolfgang and Falkenburger,
Björn H.},
title = {{E}valuation of the {E}ffect of β-{W}rapin {AS}69 in a
{M}ouse {M}odel {B}ased on {A}lpha-{S}ynuclein
{O}verexpression},
journal = {Biomolecules},
volume = {14},
number = {7},
issn = {2218-273X},
address = {Basel},
publisher = {MDPI},
reportid = {FZJ-2024-05392},
pages = {756 -},
year = {2024},
abstract = {Aggregation of the protein α-Synuclein (αSyn) is a
hallmark of Parkinson’s disease (PD), dementia with Lewy
bodies (DLB) and multiple systems atrophy, and alleviating
the extent of αSyn pathology is an attractive strategy
against neurodegeneration. The engineered binding protein
β-wrapin AS69 binds monomeric αSyn. AS69 reduces primary
and secondary nucleation as well as fibril elongation in
vitro. It also mitigates aSyn pathology in a mouse model
based on intrastriatal injection of aSyn pre-formed fibrils
(PFFs). Since the PFF-based model does not represent all
aspects of PD, we tested here whether AS69 can reduce
neurodegeneration resulting from αSyn overexpression. Human
A53T-αSyn was overexpressed in the mouse Substantia nigra
(SN) by using recombinant adeno-associated viral vector
(rAAV). AS69 was also expressed by rAAV transduction.
Behavioral tests and immunofluorescence staining were used
as outcomes. Transduction with rAAV-αSyn resulted in αSyn
pathology as reported by phospho-αSyn staining and caused
degeneration of dopaminergic neurons in the SN. The
co-expression of rAAV-AS69 did not reduce αSyn pathology or
the degeneration of dopaminergic neurons. We conclude that
αSyn monomer binding by rAAV-AS69 was insufficient to
protect from aSyn pathology resulting from αSyn
overexpression.},
cin = {IBI-7},
ddc = {570},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {39062470},
UT = {WOS:001276686300001},
doi = {10.3390/biom14070756},
url = {https://juser.fz-juelich.de/record/1030668},
}