Publication
Characterisation of PRKRA and WDR45 gene function, involved in Parkinson's disease
| datacite.subject.fos | Ciências Médicas::Ciências da Saúde | pt_PT |
| dc.contributor.advisor | Lewis, Patrick | |
| dc.contributor.advisor | Araújo, Inês | |
| dc.contributor.author | Bordone, Marie Catherine | |
| dc.date.accessioned | 2016-03-21T12:03:23Z | |
| dc.date.available | 2016-03-21T12:03:23Z | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014 | |
| dc.description | Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2014 | |
| dc.description.abstract | The PRKRA gene is situated on human chromosome 2p. It plays an important role in the regulation of gene expression in interferon–treated and virus–infected animal cells and is also implicated in the control of cell growth, proliferation and differentiation. The downstream target of this activation is a stress response protein involved in the Protein Kinase R (PKR) signalling pathway that mobilizes somatic cell death programs. It has been shown that aggregates of phosphorylated PKR are increased in the hippocampus of patients with Parkinson’s disease. The P222L mutation in this gene is associated to dystonia-parkinsonism syndrome (DYT16) although the mechanism underlying this disorder is not yet understood. BPAN (Beta propeller associatied neurodegeneration) disorder is caused by mutations in the WDR45 gene, which results in loss of function, and presents with some dystonia-parkinsonism features. This gene is situated on chromosome X (Xp11.23) and the mutations that occur are de novo, suggesting an atypical X-linked pattern disorder. WDR45 (WIPI4) belongs to the WD-40 family and is characterised by a seven-bladed β structural shape. Its ortholog in yeast is the Atg18, known to be involved in autophagy, so it is thought that WDR45 acts in the early steps of the autophagy cascade as a regulator of the ATG9A marked vesicles that transiently localize to the autophagosome formation site and induce autophagosome formation. WDR45 mutations primarily affect the brain, despite expression of the gene in several human tissues, suggesting that autophagy plays an important role in the brain. To date, WDR45 loss of function has been thought to cause impairments in autophagy, leading to a neurodevelopment and neurodegenerative phenotype. The main goals of this thesis, were to analyse if the PKR pathway was altered by overexpressing PRKRA wild-type and mutated in the HT1080 cell line and to investigate the impact of overexpressing WDR45 in H4, HEK and SHSY5 cell lines, in order to possibly provide insights with regard to the mechanisms that are underlie BPAN, DYT16 and Parkinson’s disease. These goals were performed by western blots and analyzing well known hallmarks of autophagy such as LC3 and p62. Immunocytochemistry analysis was also performed to investigate the localisation of WDR45 within the cell as well if the autophagy was induced, in standard and induced autophagy conditions. | pt_PT |
| dc.identifier.tid | 202210740 | |
| dc.identifier.uri | http://hdl.handle.net/10400.1/7889 | |
| dc.language.iso | eng | pt_PT |
| dc.subject | Ciências biomédicas | pt_PT |
| dc.subject | Doença de Parkinson | pt_PT |
| dc.subject | Proteínas | pt_PT |
| dc.subject | Mutações | pt_PT |
| dc.subject | Autofagia | pt_PT |
| dc.subject | Marcadores | pt_PT |
| dc.title | Characterisation of PRKRA and WDR45 gene function, involved in Parkinson's disease | pt_PT |
| dc.type | master thesis | |
| dspace.entity.type | Publication | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | masterThesis | pt_PT |
| thesis.degree.grantor | Universidade do Algarve. Departamento de Ciências Biomédicas e Medicina | |
| thesis.degree.level | Mestre | |
| thesis.degree.name | Mestrado em Ciências Biomédicas | pt_PT |
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