Alpha-synuclein is an abundantly expressed neuronal protein that is at the center of focus in understanding a group of neurodegenerative diseases called synucleinopathies. The common feature of synucleinopathies is the presence of intracellular bodies containing aggregates of alpha-synuclein. Two important synucleinopathies are multiple system atrophy (MSA) and Parkinson’s disease (PD). MSA and PD share common clinical and pathological features, and both cause decreased bodily movement. The human brain is extremely rich in lipids (commonly known as fats), such as cholesterol. Stable maintenance of lipids is increasingly recognized as a crucial factor for normal brain function, and growing evidence shows that altered lipid levels and/or distribution are contributory factors in a number of neurodegenerative diseases.
However, little is known about the role of lipids in the pathological processes of synucleinopathies. Here at the University of Sydney, we have produced compelling evidence showing that lipid levels are significantly altered in disease-affected regions of MSA and PD brains. Our data indicate that dysregulation of lipids in the brain contribute to cell instability and neurodegeneration. Our current studies aim to understand the factors and pathways underlying the lipid changes in synucleinopathies, especially the impact of lipid changes on α-synuclein aggregation process. We are endeavoring to understand the role of a number of lipid genes that have been newly identified. Our group is internationally in a strong position to advance this field because of our access to post-mortem MSA and PD brain tissues. We envisage our research will reveal new molecular targets and pathways that could be exploited to develop potential therapeutic avenues for the treatment of MSA and PD.
Professor Kim’s recent research has been funded by the MSA United International Research Consortium and its US member, Defeat MSA Alliance in 2022. For more information on the Consortium, please visit: www.msaunited.org