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Transmission of pathogenic α-synuclein to mice

dc.contributor.advisorTamgüney, Gültekin
dc.contributor.authorBreid, Sara
dc.date.accessioned2020-04-23T23:57:24Z
dc.date.available2020-04-23T23:57:24Z
dc.date.issued01.09.2017
dc.identifier.urihttp://hdl.handle.net/20.500.11811/7209
dc.description.abstractα-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.
dc.language.isoeng
dc.rightsIn Copyright
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectα-synuclein
dc.subjectTransmission
dc.subjectintraperitoneal
dc.subjectintraglossal
dc.subjectAerosole
dc.subjectNeuroinflammation
dc.subjectaerosols
dc.subject.ddc570 Biowissenschaften, Biologie
dc.subject.ddc610 Medizin, Gesundheit
dc.titleTransmission of pathogenic α-synuclein to mice
dc.typeDissertation oder Habilitation
dc.publisher.nameUniversitäts- und Landesbibliothek Bonn
dc.publisher.locationBonn
dc.rights.accessRightsopenAccess
dc.identifier.urnhttps://nbn-resolving.org/urn:nbn:de:hbz:5n-47847
ulbbn.pubtypeErstveröffentlichung
ulbbnediss.affiliation.nameRheinische Friedrich-Wilhelms-Universität Bonn
ulbbnediss.affiliation.locationBonn
ulbbnediss.thesis.levelDissertation
ulbbnediss.dissID4784
ulbbnediss.date.accepted2017-06-12
ulbbnediss.instituteAngegliederte Institute, verbundene wissenschaftliche Einrichtungen : Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
ulbbnediss.fakultaetMathematisch-Naturwissenschaftliche Fakultät
dc.contributor.coRefereeHöhfeld, Jörg


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