| dc.contributor.advisor | Kügler, Sebastian Dr. | |
| dc.contributor.author | Toloe, Johan | |
| dc.date.accessioned | 2014-09-25T07:23:50Z | |
| dc.date.available | 2014-09-25T07:23:50Z | |
| dc.date.issued | 2014-09-25 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0023-98DB-7 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-4651 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Effects of α/β/γ-Synuclein overexpression on the mitochondria and viability of neurons, examined using genetically encoded fluorescent sensors | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Mironov, Sergej Dr. | |
| dc.date.examination | 2014-01-27 | |
| dc.description.abstracteng | Parkinson’s disease (PD) is the second most common neurodegenerative disease and it affects more than 1% of the worlds population over the age of 65. A hallmark of PD is the appearance of Lewy bodies (LBs) throughout the brain and a major component of these intracellular inclusions is the small soluble protein α-Synuclein (αS). Rare familial mutations as well as duplications and triplications of the gene coding for αS leads to early onset PD and this makes a role for αS in the etiology of PD likely but exactly how αS contributes to the disease is still unknown. No genetic link to PD has so far been described for the other two members of the synuclein family, β-Synuclein (βS) and γ-Synuclein (γS) but βS has recently been suggested to have neuroprotective properties, evidence of which comes from experiments showing that it reduces αS induced neurotoxicity. However, a mutation in βS is linked to dementia with Lewy bodies (DLB) and has been shown to cause neurodegeneration in transgenic (TG) mice. For this thesis, the effects of overexpression of the synucleins in primary cortical neurons were examined. Because αS has been shown to reduce the activity of complex I of the electron transport chain (ETC) in mitochondria isolated from patients, a special interest was the effects on the mitochondria, its function and morphology. Overexpression of αS as well as βS but not γS led to degeneration of neurons. The mitochondria was also affected, αS and βS both led to a fragmented morphology that worsened with time whereas the mitochondria in γS overexpressing neurons were unaffected. Nevertheless, these mitochondria were still functionally intact. Not only were they able to handle influx of calcium, they were also able to regenerate ATP after depletion at the same rate as control. This suggests that oxidative phosphorylation and as a consequence complex I is not significantly impaired in these neurons. Therefore, the toxicity of αS is not likely to be due to a direct impairment of mitochondrial function. The fact that βS has similar effects as those of αS in terms of toxicity and
mitochondrial morphology was new and suggests a role for βS in PD that will require further
study. | de |
| dc.contributor.coReferee | Moser, Tobias Prof. Dr. | |
| dc.subject.eng | synuclein; synucleinopathy; neurodegeneration; cell culture; fluorescence; sensors; quantitative microscopy; genetically encoded sensor; genetically encoded indicator; genetically encoded calcium sensor; microscopy; toxicity; alpha synuclein; beta synuclein; gamma synuclein; field stimulation; atp sensor; calcium sensor; tmrm; disease; parkinsons; parkinsons disease; neuroscience | de |
| dc.subject.eng | atp measurement | de |
| dc.subject.eng | calcium measurement | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0023-98DB-7-2 | |
| dc.affiliation.institute | Biologische Fakultät für Biologie und Psychologie | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 797480390 | |