Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.771828
Title: Mitochondrial function, oxidative stress and Parkinson's disease
Author: Al Shahrani, Mesfer M.
ISNI:       0000 0004 7659 9777
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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Abstract:
The loss of the activity of mitochondrial respiratory chain (MRC) complexes, particularly complex I, has been implicated in Parkinson's disease (PD) pathogenesis. However, it is still uncertain whether altered MRC activity is an early event in the pathophysiology of PD, or a late consequence of cellular stress. Therefore, this thesis contributes differently from other studies as to the ongoing investigations about MRC activity in PD post-mortem brain based on pathological severity. This study demonstrates that loss of complex I activity occurs in regions with both moderate and mild pathology in PD brain. Furthermore, multiple complex defects were noted in the moderate pathology region. However, the activity of complex II which is entirely encoded by nuclear DNA appeared to be preserved. The exact mechanism of multiple complex defects remain elusive. However, the possibility arises that impairment of complex I results in secondary damage to the other complexes. Here, neuroblastoma cells were employed to study the effect of pharmacologically induced MRC complex I deficiency upon the activity of the other complexes. In this model, rotenone-treated (100 nM; 24-48 hours) SH-SY5Y cells induced an inhibition of complex I. At 24 hours no effect was observed on the other complexes. However at 48 hours, multiple complex defects were noted, but the activity of complex II appeared to be preserved. Additionally, bioenergetics and glutathione status were compromised. By utilizing this model, the effectiveness of antioxidants in alleviating the progression of complex I deficiency on other complexes were also evaluated. Furthermore, the use of the Oxygraph-2K® instrument together with a step-wise protocol was developed to assess the integrated mitochondrial function in cultured SH-SY5Y cells. Additionally, the focus of attention was also to validate the fibroblast growth factor-21 ELISA assay. Based on the results, this assay appears to be a useful as a biomarker for mitochondrial dysfunction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.771828  DOI: Not available
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