Breid, Sara: Transmission of pathogenic α-synuclein to mice. - Bonn, 2017. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
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author = {{Sara Breid}},
title = {Transmission of pathogenic α-synuclein to mice},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2017,
month = sep,

note = {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.},
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