Researchers have used computational models to understand what drives the accumulation of alpha-synuclein protein, a key culprit in the development of Parkinson's disease.
"A growing body of evidence has established a connection between intrinsically disordered proteins and liquid-liquid phase separation, or LLPS, the phenomenon you see if you mix oil and water," says lead author Abdul Wasim, a PhD student at the Tata Institute of Fundamental Research, Hyderabad, India."This is of interest because LLPS is itself known to form subcellular compartments that can lead to incurable diseases.
Using this model, the authors simulated the collective interaction of many alpha-synuclein chains within droplets under different conditions. First, by studying the protein chains mixed only with water, they found that around 60% of the protein chains remained free and did not show a strong and spontaneous tendency to aggregate together.
A characteristic of LLPS is that the protein molecules within droplets adopt an extended shape and all orient themselves in a consistent direction. So, the team next set out to see if this was true within their simulations.
"Together, these results suggest that both crowder molecules and salt enhance the aggregation of alpha-synuclein, while also stabilising the resulting aggregates," says Wasim."Irrespective of the factors causing the aggregation, the interactions that drive the formation of droplets remain the same."