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@ARTICLE{Frieg:912258,
author = {Frieg, Benedikt and Geraets, James A. and Strohäker, Timo
and Dienemann, Christian and Mavroeidi, Panagiota and Jung,
Byung Chul and Kim, Woojin S. and Lee, Seung-Jae and
Xilouri, Maria and Zweckstetter, Markus and Schröder,
Gunnar F.},
title = {{Q}uaternary structure of patient-homogenate amplified
α-synuclein fibrils modulates seeding of endogenous
α-synuclein},
journal = {Communications biology},
volume = {5},
number = {1},
issn = {2399-3642},
address = {London},
publisher = {Springer Nature},
reportid = {FZJ-2022-05455},
pages = {1040},
year = {2022},
abstract = {Parkinson’s disease (PD) and Multiple System Atrophy
(MSA) are progressive and unremitting neurological diseases
that are neuropathologically characterized by α-synuclein
inclusions. Increasing evidence supports the aggregation of
α-synuclein in specific brain areas early in the disease
course, followed by the spreading of α-synuclein pathology
to multiple brain regions. However, little is known about
how the structure of α-synuclein fibrils influence its
ability to seed endogenous α-synuclein in recipient cells.
Here, we aggregated α-synuclein by seeding with homogenates
of PD- and MSA-confirmed brain tissue, determined the
resulting α-synuclein fibril structures by cryo-electron
microscopy, and characterized their seeding potential in
mouse primary oligodendroglial cultures. The combined
analysis shows that the two patient material-amplified
α-synuclein fibrils share a similar protofilament fold but
differ in their inter-protofilament interface and their
ability to recruit endogenous α-synuclein. Our study
indicates that the quaternary structure of α-synuclein
fibrils modulates the seeding of α-synuclein pathology
inside recipient cells. It thus provides an important
advance in the quest to understand the connection between
the structure of α-synuclein fibrils, cellular
seeding/spreading, and ultimately the clinical
manifestations of different synucleinopathies.},
cin = {IBI-7},
ddc = {570},
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 = {36180728},
UT = {WOS:000862402500005},
doi = {10.1038/s42003-022-03948-y},
url = {https://juser.fz-juelich.de/record/912258},
}