|Institution:||University of New South Wales|
|Keywords:||Parkinson's disease; ABCA5|
|Full text PDF:||http://handle.unsw.edu.au/1959.4/53075|
Parkinson‟s disease (PD) is one of the most common neurological movement disorders in humans. Its pathological hallmark is the deposition of intracellular aggregates of the neuronal protein α-synuclein. Increasing evidence indicates that α-synuclein binds and interacts with lipids, which are transported in the central nervous system (CNS) by a group of proteins called ATP-Binding Cassette subfamily A (ABCA) transporters. A genome-wide association study reported that ABCA5 is associated with PD. However, very little is known about the function of ABCA5 in the brain or PD. The aim of this project is to investigate the potential function of ABCA5 in the brain and in the disease process of PD. This was achieved by analyzing changes in ABCA5 expression in samples of human post-mortem PD brain compared with age- and gender- matched disease-free controls, and by assessing PD relevant molecular changes in in vitro models transiently expressing ABCA5. In the anterior cingulate cortex, ABCA5 gene expression, but not the expression of other ABCA transporters, was significantly reduced in PD compared to controls. The levels of α-synuclein expression were also significantly decreased in the same region as ABCA5. Moreover, SK-N-SH neuronal cells transiently transfected with ABCA5 demonstrated significantly up-regulated α- synuclein mRNA expression with no increase in α-synuclein protein levels. Transiently expressed ABCA5 was also shown to stimulate the efflux of cholesterol from neurons to discs made from apolipoproteinE. Upregulation of ABCA5 gene expression could be stimulated by peroxisome proliferator-activated receptor (PPAR) in a time- and dose-dependent manner. These findings suggest that ABCA5 may be involved in regulation of lipid homeostasis in the pathological process of PD.