eprintid: 10064465
rev_number: 33
eprint_status: archive
userid: 608
dir: disk0/10/06/44/65
datestamp: 2019-01-30 14:36:28
lastmod: 2023-03-01 07:10:11
status_changed: 2019-01-30 14:36:28
type: thesis
metadata_visibility: show
creators_name: Al Shahrani, Mesfer M.
title: Mitochondrial Function, Oxidative Stress and Parkinson's Disease
ispublished: unpub
divisions: UCL
note: Copyright © The Author 2018.  Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/).  Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms.  Access may initially be restricted at the author’s request. - Third party copyright material has been removed from this e-thesis.
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.
date: 2018-12-28
date_type: published
oa_status: green
full_text_type: other
thesis_class: doctoral_embargoed
thesis_award: Ph.D
language: eng
thesis_view: UCL_Thesis
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1613963
lyricists_name: Al Shahrani, Mesfer
lyricists_id: MMAAL87
actors_name: Al Shahrani, Mesfer
actors_id: MMAAL87
actors_role: owner
full_text_status: public
pages: 390
event_title: UCL
institution: UCL (University College London)
department: UCL GOS Institute of Child Health
thesis_type: Doctoral
citation:        Al Shahrani, Mesfer M.;      (2018)    Mitochondrial Function, Oxidative Stress and Parkinson's Disease.                   Doctoral thesis  (Ph.D), UCL (University College London).     Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10064465/1/Al%20Shahrani_10064465_thesis_redacted.pdf