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@PHDTHESIS{Breid:144786,
author = {Breid, Sara},
title = {{T}ransmission of pathogenic alpha-synuclein to mice},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
type = {Dissertation},
address = {Bonn},
reportid = {DZNE-2020-00229},
pages = {111 pages},
year = {2017},
note = {Dissertation, Rheinische Friedrich-Wilhelms-Universität
Bonn, 2017},
abstract = {α-Synuclein is a soluble, cellular protein that in a
number of neurodegenerative diseases, including Parkinson's
disease, multiple system atrophy, and Lewy body dementia
aggregates into pathological protein deposits. Principles
how misfolded and aggregated α-synuclein is transmitted
within the central nervous system (CNS) causing neurologic
disease were found to be similar to those of prions.
Misfolded α-synuclein can be transmitted between cells and
act as a seed, recruiting native, unfolded α-synuclein to
form insoluble aggregates. The mechanisms and the routes
through which pathogenic proteins enter the CNS causing
progressive disease are still not completely understood. The
work in this thesis confirms previous findings indicating
that α-synuclein fibrils intracerebrally injected into
wild-type mice for α-synuclein can induce neuropathology in
interconnected brain regions as similarly observed in
sporadic Parkinson's disease. In contrast, α-synuclein
fibrils injected into the tongue muscle of wild-type mice
for α-synuclein did not neuroinvade the CNS causing
α-synuclein pathology. Moreover, the present study is the
first to show, that α-synuclein fibrils peripherally
injected into the tongue and the peritoneum of mice
overexpressing human α-synuclein, can neuroinvade the CNS,
cause widespread α-synuclein pathology and induce
neurologic symptoms. The induction of neuropathology was
accompanied by neuroinflammation as monitored by astrocytic
gliosis and microgliosis. In addition, the study presented
here indicates that exposure of mice overexpressing human
α-synuclein with pathogenic α-synuclein aerosols was not
sufficient for α-synuclein prionoids to enter the brain via
the olfactory epithelium and induce neuropathology. In
summary, these findings corroborate the prionoid character
of misfolded α-synuclein using similar routes like prions
to neuroinvade brain and spinal cord and induce neurologic
disease.},
cin = {AG Tamgüney},
cid = {I:(DE-2719)1013022},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)11},
urn = {urn:nbn:de:hbz:5n-47847},
url = {https://pub.dzne.de/record/144786},
}