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|Authors: ||Zilocchi, Mara|
|Internal Tutor: ||FASANO, MAURO|
|Title: ||Discovering mithocondrial alterations in Parkinson's disease: the role of mitophagy impairment.|
|Abstract: ||Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders, characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta. Although the cause of PD is currently unknown, strong evidences indicate that a complex interplay between several factors including genetic susceptibility, environmental factors, abnormal protein handling and oxidative stress could be involved. Many of the molecular pathways implicated in PD etiology converge on mitochondria, resulting in their dysfunction, which could impact on neuronal survival.
Given the importance of mitochondrial dysfunctions in PD, we decided to investigate the missed removal of damaged mitochondria due to mitophagy impairment as the possible trigger of pathogenesis. To this purpose, we characterized specific mitochondrial alterations in Substantia nigra specimens from PD patients, comparing them to what observed by inducing mitochondrial impairment in human neuroblastoma SH-SY5Y cells using dopamine or MPP+.
Since mitophagy impairment seems to play a central role in the development of this pathology, the second part of this thesis focused on mitochondrial alterations that occur in skin fibroblasts obtained from PARK2-mutated patients. As a result, we found that mutations in the PARK2 gene do not cause any significant morphological alterations in the mitochondrial network shape. Moreover, the proteomics analysis revealed an impairment of proteins involved in several mitochondrial functions.
Overall, this project contributes to a complete definition of the PARK2-related molecular signature, that will be crucial for providing new insights into disease mechanisms and identifying new therapeutic targets for this pathology.|
|Keywords: ||Parkinson's disease, mitochondria, dopamine, MPP+, proteomics, interatomics, PARK2|
|Subject MIUR : ||BIO/10 BIOCHIMICA|
|Issue Date: ||2018|
|Doctoral course: ||Medicina sperimentale e traslazionale|
|Academic cycle: ||30|
|Publisher: ||Università degli Studi dell'Insubria|
|Citation: ||Zilocchi, M.Discovering mithocondrial alterations in Parkinson's disease: the role of mitophagy impairment. (Doctoral Thesis, Università degli Studi dell'Insubria, 2018).|
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