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Please use this identifier to cite or link to this item: http://hdl.handle.net/10277/895

Authors: Colugnat, Ilaria
Internal Tutor: FASANO, MAURO
Title: Parkinson’s disease and mitochondrial disfunctions: exploring the effect of PARK2 mutations in human skin fibroblasts
Abstract: Parkinson’s disease is a complex and multifactorial neurodegenerative disease whose etiology has not been totally clarified yet. Strong evidences suggest that a complex interplay between environmental and genetic factors are involved in PD pathogenesis. Many of the molecular pathways implicated in PD etiology converge on mitochondria, resulting in their dysfunction. Mutations in PARK2 gene are the most frequent cause of familial forms of PD. This gene encodes Parkin, an E3 ubiquitin ligase involved in the mitophagy process. Parkin loss-of-function is responsible for the cellular accumulation of damaged mitochondria. Given the importance of mitochondrial dysfunctions and mitophagy impairment in PD pathogenesis, PARK2-mutated primary skin fibroblasts were used as a cellular model to explore the effects of PARK2 mutations both on the mitochondrial function and morphology and on the total and mitochondrial proteome. The first part of this thesis investigates the impact of Parkin impairment on mitochondrial function and network in primary skin fibroblasts of five PARK2 patients and five control subjects. The second part of this project is focused on the characterization of the mitochondrial and the total proteome alterations that characterize patients carrying PARK2 mutations. In conclusion, the present work highlighted new molecular factors and pathways altered by PARK2 mutations, which will unravel possible biochemical pathways altered in the sporadic form of the disease. The Peptide Transporters of teleost fish, an emerging model in translational research: functional characterization and comparative study of SLC15A1a (PepT1a) and SLC15A1b (PepT1b) transporters.
Keywords: Proteomic altyerations, mitophagy, mitochondria, Parkinson's disease, Parkin
Subject MIUR : BIO/10 BIOCHIMICA
Issue Date: 2020
Language: eng
Doctoral course: Medicina sperimentale e traslazionale
Academic cycle: 32
Publisher: Università degli Studi dell'Insubria
Citation: Colugnat, I.Parkinson’s disease and mitochondrial disfunctions: exploring the effect of PARK2 mutations in human skin fibroblasts (Doctoral Thesis, Università degli Studi dell'Insubria, 2020).

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