Shake It Up recently announced funding for a new research project investigating quantitative mapping of aSyn soluble and insoluble PTMs in selected brain regions and cell types as a function of disease progression and in familial synucleinopathies, led by Professor Glenda Halliday, PhD, at University of Sydney.
We spoke with Professor Halliday to learn more about this project and what it means for people living with Parkinson’s now, and in the future.
Can you explain for people outside the scientific community, what does “aSyn soluble and insoluble PTMs” mean?
Alpha-synuclein, or aSyn, is a normal protein found in the brain. It has different functions depending on how it’s modified chemically by enzymes (known as posttranslational modifications or PTMs). These PTMs change how aSyn interacts with other proteins and lipids in the brain. Importantly PTMs occur in high abundance in the insoluble pathological aggregates of aSyn present in people with Parkinson’s. We don’t know the role of these modifications in regulating how these insoluble pathological aggregates form, their toxicity, or how they spread in the brain during disease progression, so our research should give insight into their role and point to enzymes whose activity may be able to be modified.
Can you give a brief explanation of this recently funded research project for our community?
The project will first develop protocols for isolating and handling aSyn species from human brain tissues while preserving their biochemical diversity (PTMs) and assess all the PTMs on aSyn. The project will then study where these different types of aSyn are found in intact tissues in multiple brain regions and different cell types (neurons, astrocytes, and oligodendrocytes) at different stages of disease progression. Overall the project will build a picture of what chemical steps are necessary for aSyn to become pathological and where in the brain these steps occur.
How will this project help your research team understand more about Parkinson’s disease progression?
The research project will focus on a single aspect of the biochemical progression of Parkinson’s in the brain. The project will determine how and where the different aSyn PTMs develop to cause pathology in Parkinson’s, and then map how they progress through the brain.
What is the expected impact of this research project for people living with Parkinson’s?
The immediate impact for people with Parkinson’s is greater knowledge about the disease. In particular, it will give us a better understanding of what chemical modifications are most important for turning normal brain protein into something pathological. Knowing more about the biochemistry of aSyn is likely to assist with diagnostic biomarkers and understanding what enzymes may be involved could lead to potential future therapies.
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