Der Einfluss von humanem α-Synuclein-Wildtyp und der Mutanten A30P und A53T auf die Autophagie und den Transport synaptischer Vesikel in primären Mittelhirnneuronen der Ratte
The influence of human α-Synuclein-wildtype and its mutants A30P and A53T on autophagy and transport of synaptic vesicles in rat primary midbrain neurons
von Florian Bitow
Datum der mündl. Prüfung:2020-10-07
Erschienen:2020-09-29
Betreuer:PD Dr. Jan C. Koch
Gutachter:PD Dr. Jan C. Koch
Gutachter:Prof. Dr. Thomas Dresbach
Dateien
Name:Dissertation Florian Bitow.pdf
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Description:Dissertation
Zusammenfassung
Englisch
Despite the expanding pathological understanding of Parkinson´s disease (PD) the relevant pathomechanisms are still not completely understood. Previous evidence suggests that disturbed cellular proteindegradation (autophagy) is important in pathology of PD, other studies showed a cellular degeneration starting from the axon and moving backwards to the cell body (dying back), indicating that changes as well in macro- and chaperon-mediated autophagy (CMA) as alterations in the axonal transport require further research. Therefore, an in-vitro modell of rat primary midbrain neurons overexpressing α-Synuclein-wildtype (WT) and its mutants A30P and A53T were analysed more intensively. Here α-Synuclein-WT gains macroautophagy and CMA independent to the analysed cell population whereas the A53T-mutation only causes an increased macroautophagy in dopaminergic neurons. The A30P-mutations even reduces macroautophagy in tendency independent to the analysed cell population and doesn´t change CMA as well. Analysis of axonal transport showed a reduced amount of moving vesicles and decelerated overall speed in all α-Synuclein populations compared to control group. In conclusion α-Synuclein has been shown to cause alterations as well in autophagy as in axonal transport, too and these mechanisms are relevant for pathology of PD.
Keywords: α-Synuclein; autophagy; axonal transport