The consequences of structural and functional modification of tyrosine hydroxylase

The major focus of this thesis is an analysis of the localisation and protein binding of the human tyrosine hydroxylase isoforms. The human TH isoforms were identified over 30 years ago. Despite that, there are still many questions as to the roles the different isoforms play and why humans have retained all four isoforms. The work in this thesis aims to increase our understanding of the roles of the human TH isoforms and in particular isoforms that are only found in humans. This work focused on a comparison between TH isoform 1 which is found in all mammals and TH isoform 4 which is only found in humans. A second focus of the thesis is an analysis of possible post-translational modifications of TH that occur in an animal model of Parkinson’s disease. In this section the focus is on an inflammatory model of Parkinson’s disease and the aim was to understand the mechanism of the unusual activation of TH seen in this model that is not due to TH phosphorylation. The three specific aims of the thesis are set out below, together with chapter in which the work is reported.