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001     144786
005     20250718162053.0
024 7 _ |a urn:nbn:de:hbz:5n-47847
|2 URN
037 _ _ |a DZNE-2020-00229
041 _ _ |a English
100 1 _ |a Breid, Sara
|0 P:(DE-2719)2810477
|b 0
|e First author
|u dzne
245 _ _ |a Transmission of pathogenic alpha-synuclein to mice
|f - 2017-06-12
260 _ _ |a Bonn
|c 2017
300 _ _ |a 111 pages
336 7 _ |a Output Types/Dissertation
|2 DataCite
336 7 _ |a DISSERTATION
|2 ORCID
336 7 _ |a PHDTHESIS
|2 BibTeX
336 7 _ |a Thesis
|0 2
|2 EndNote
336 7 _ |a Dissertation / PhD Thesis
|b phd
|m phd
|0 PUB:(DE-HGF)11
|s 1752848396_2393
|2 PUB:(DE-HGF)
336 7 _ |a doctoralThesis
|2 DRIVER
502 _ _ |a Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn, 2017
|c Rheinische Friedrich-Wilhelms-Universität Bonn
|b Dissertation
|d 2017
520 _ _ |a 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.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
|0 G:(DE-HGF)POF3-342
|c POF3-342
|f POF III
|x 0
856 4 _ |u https://hdl.handle.net/20.500.11811/7209
856 4 _ |u https://pub.dzne.de/record/144786/files/DZNE-2020-00229_Restricted.pdf
856 4 _ |u https://pub.dzne.de/record/144786/files/DZNE-2020-00229_Restricted.pdf?subformat=pdfa
|x pdfa
909 C O |p VDB
|o oai:pub.dzne.de:144786
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 0
|6 P:(DE-2719)2810477
913 1 _ |a DE-HGF
|b Gesundheit
|l Erkrankungen des Nervensystems
|1 G:(DE-HGF)POF3-340
|0 G:(DE-HGF)POF3-342
|3 G:(DE-HGF)POF3
|2 G:(DE-HGF)POF3-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms and Model Systems
|x 0
914 1 _ |y 2017
920 _ _ |l yes
920 1 _ |0 I:(DE-2719)1013022
|k AG Tamgüney
|l Prion and prion-like diseases
|x 0
980 _ _ |a phd
980 _ _ |a VDB
980 _ _ |a I:(DE-2719)1013022
980 _ _ |a UNRESTRICTED

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