Year: 2015
Type: dissertation
Abstract: This dissertation involves a genetic and functional investigation of parkin and its role in Parkinson's disease (PD).As such, it examines the contribution of parkin mutations to PD in South African patients, highlights novel parkin-interacting proteins and evaluates cellular function in a parkindeficient cell model.Furthermore, it explores the therapeutic compound vitamin K2 as a possible PD treatment modality.This dissertation is divided into four chapters:Chapter one provides an overview of what is currently known about PD, with a particular emphasis on the genetics and pathobiology of this disease.As this dissertation will be specifically focusing on the role of parkin in PD, a review of the literature on parkin is provided.Previous studies on the therapeutic potential of vitamin K2 for PD will also be highlighted.Lastly, the overall aims and objectives of this study will be outlined.Chapter two details the methodological approaches used in this dissertation, and is organized into three parts.The first part describes a molecular genetic screen of parkin for pathogenic mutations, the second part entails experimental procedures used to identify and characterize parkin-interacting proteins, and the third part provides methods employed in the functional evaluation of cellular health in a model of parkin deficiency.Chapter three relays the results obtained from the present study.It includes the findings on the frequency of parkin mutations South African PD patients, the identification and verification of four parkin interactors, interesting cellular phenotypes observed in a parkin-deficient cell model and describes the effect of treatment with vitamin K2 on several parameters of cellular health.Chapter four provides a discussion of the important findings of this dissertation, and highlights the possible relevance of these findings to PD research.It furthermore advises on proposed future work that may expand our current understanding of parkin and its role in PD.
Author: William Haylett
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2265710356