|Title:||Mitochondrial Dysfunction and the Role of PGC-1a in Genetic Parkinson’s Disease|
|Authors:||Ha, Ainhi Duy|
|Publisher:||University of Sydney.|
Kolling Institute of Medical Research.
Northern Clinical School.
|Abstract:||There is increasing evidence to suggest that mitochondrial dysfunction plays a key role in the patho-physiology of Parkinson’s Disease (PD). The transcriptional coactivator PGC-1alpha is considered to be a master regulator of mitochondrial biogenesis, with several of its transcription targets involved in the transcriptional expression of mitochondrial respiratory proteins. This project aimed to characterize the mitochondrial phenotype in three autosomal recessive PD genes, PINK1 (PARK6), parkin (PARK2), and ATP13A2 (PARK9), as well as the autosomal dominant gene LRRK2 (PARK8), in a patient-derived neural cell model. The role of PGC-1alpha was also examined in relation to the mitochondrial dysfunction. Disease-specific alterations in mitochondrial phenotype were demonstrated in human olfactory neurospheres (hONs) harbouring different PD gene mutations. PGC-1alpha did not appear to play a significant role in the mitochondrial dysfunction in the genetic PD hONs. Overexpression of PGC-1alpha did not significantly improve the mitochondrial phenotype in these cells. Characterisation of the mitochondrial phenotype in the individual PD mutants allows further understanding of the molecular mechanisms underlying the disease process in each of the mutations, with the potential to facilitate the development of disease-specific neuroprotective therapies.|
|Access Level:||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.|
|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|HA Ainhi - Final thesis.pdf||10.14 MB||Adobe PDF|
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