Distinguishing Parkinson’s Disease from other Parkinsonian disorders through a proteomics approach using PBMCs

• Autor(a) principal: Duarte, Diana Branco
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/39602
• topic: Neurodegenerative dsease; Parkinson disease; Parkinsonisms; Peripheral blood mononuclear cells; Proteomics and mass spectometry

Parkinson’s Disease (PD) is the second most common neurodegenerative disease after Alzheimer’s Disease. Besides PD, there are also other types of parkinsonism, which differ from PD in certain features, but have very similar symptoms which makes it very difficult to distinguish and diagnose them. Therefore, there is a necessity to create new and better ways to distinguish and diagnose the different parkinsonisms. Peripheral Blood Mononuclear Cells (PBMC) are a good source for biomarkers since they are able to mimic the biological changes that are occurring at disease sites through the immune response that they produce. Additionally, neuroinflammation associated with neurodegenerative diseases is known to damage the blood-brain barrier, facilitating the entry of PBMCs into the central nervous system, which makes these cells a potential source of biomarkers for parkinsonism. Thus, the objectives of this project are, first perform a batch effect correction on two preexistent batches, and then, characterize PBMCs from patients with PD and the other parkinsonian disorders using a liquid chromatography coupled to mass spectrometry proteomics approach. The results will be integrated in a biological context using bioinformatics tools, and it will be identified the proteins that are deregulated and could be potential biomarkers for distinguishing these diseases. For this study, 4 comparisons were performed: control vs disease; PD vs atypical parkinsonism; control vs PD; and control vs atypical parkinsonism. For each of the comparisons, it was not only performed a statistical analysis for the proteins with most statistical relevance, but also a Gene Ontology analysis, where the results suggested a deregulation of protein synthesis associated with parkinsonism. A biomarker analysis was also performed for the four comparisons that, in turn, allowed the identification of several proteins with potential to became biomarkers for the diseases being studied.