| dc.contributor.advisor | Stegmüller, Judith Dr. | |
| dc.contributor.author | Brockelt, David | |
| dc.date.accessioned | 2016-08-29T09:48:13Z | |
| dc.date.available | 2016-08-29T09:48:13Z | |
| dc.date.issued | 2016-08-29 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0028-881A-3 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-5833 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | The role of the E3 ubiquitin ligase FBXO7-SCF in early-onset Parkinson's disease | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Stegmüller, Judith Dr. | |
| dc.date.examination | 2015-11-19 | |
| dc.description.abstracteng | Parkinson's disease (PD) is a debilitating movement disorder. Growing evidence associates genes with familial forms of the disease. Recently, gene mutations in the FBXO7 (PARK15) gene have been identified in patients with early-onset parkinsonism symptoms and pyramidal tract signs. PARK15 encodes for the E3 ubiquitin ligase FBXO7, whose function in the brain remains to be elucidated. In this study, I report that systemic loss of FBXO7 in mice results in an early-onset motor phenotype and premature death, reminiscent of the PARK15 patients. In neuropatholgical analyses, I find a regional increase in cell death and widespread astrogliosis. At the molecular level, I demonstrate the binding of FBXO7 to the proteasomal core subunit PSMA2 and identify PSMA as non-proteolytic ubiquitination substrate. Interestingly, I show that loss of FBXO7 in the brain leads to reduced proteasome activity as a consequence of defective proteasome integrity. Taken together, I established an FBXO7- dependent mechanism of proteasome regulation in neurons, which provides novel insight into the role of the UPS in PD. | de |
| dc.contributor.coReferee | Outeiro, Tiago Fleming Prof. Dr. | |
| dc.subject.eng | Biology | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0028-881A-3-3 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 869469509 | |