dc.contributor.author | Popovitchenko, Tatiana | |
dc.date.accessioned | 2015-01-22T09:59:41Z | |
dc.date.available | 2015-01-22T09:59:41Z | |
dc.date.issued | 2014-06-16 | |
dc.identifier.uri | http://hdl.handle.net/11250/274535 | |
dc.description | Master's thesis in Biological chemistry | nb_NO |
dc.description.abstract | One of the most common manifestations of dopaminergic degeneration in humans is in Parkinson’s Disease (PD). Although dopaminergic degeneration affects a significant portion of the aging population, the pathways and mechanisms underlying it have not yet been elucidated.
The Doitsidou lab has recently established a model of dopaminergic degeneration in Caenorhabditis elegans. In this model, a Transient Receptor Potential (TRP) channel (TRP-4) has mutated and results in a gain of function. Based on the morphology of the dopaminergic neurons, the overactive channel is believed to be activating a necrotic cell death pathway.
This thesis aims to identify the pathways relevant to TRP-4 mediated dopaminergic de-generation in Caenorhabditis elegans. It takes a two-pronged approach, comparing TRP-4 degeneration to other models of neurodegeneration and conducting a forward genetic screen to identify novel candidates.
Through these approaches, the nature of TRP-4 degeneration has been further eluci-dated. The results gathered in this thesis explore the involvement of lysosomal acidifica-tion through the V-ATPase pump in dopaminergic cell death and are not conclusive as to whether or not the V-ATPase pump plays a role in TRP-4 induced degeneration. The lysosomal biogenesis pathway is implicated in dopaminergic degeneration in the TRP-4 model. Differences in lysosomal morphology in dopaminergic neurons are established between the wild type and degenerating states. Finally, three full and three partial sup-pressors of degeneration were discovered through the automated forward genetic screen. Together, this thesis brings insight into intracellular the mechanisms underlying a novel, TRP-channel based model of dopaminergic degeneration.
3 | nb_NO |
dc.language.iso | eng | nb_NO |
dc.publisher | University of Stavanger, Norway | nb_NO |
dc.relation.ispartofseries | Masteroppgave/UIS-TN-IMN/2014; | |
dc.subject | biologisk kjemi | nb_NO |
dc.subject | dopaminergic degeneration | nb_NO |
dc.subject | Parkinson’s disease | nb_NO |
dc.subject | lysosome | nb_NO |
dc.subject | cell death | nb_NO |
dc.subject | autophagy | nb_NO |
dc.subject | necrosis | nb_NO |
dc.subject | neurodegeneration | nb_NO |
dc.subject | molekylær biologi | nb_NO |
dc.subject | cellebiologi | nb_NO |
dc.title | Mechanisms of TRP-channel mediated dopaminergic degeneration in C. elegans | nb_NO |
dc.type | Master thesis | nb_NO |
dc.subject.nsi | VDP::Mathematics and natural science: 400::Basic biosciences: 470::Biochemistry: 476 | nb_NO |
dc.subject.nsi | VDP::Mathematics and natural science: 400::Chemistry: 440::Organic chemistry: 441 | nb_NO |
dc.subject.nsi | VDP::Mathematics and natural science: 400::Basic biosciences: 470::Molecular biology: 473 | nb_NO |