European scientists have developed a simple and cheap way to study protein aggregation in Parkinson's disease.

Parkinson's is a progressive disease that affects coordination of movement in sufferers. The condition results from a loss of dopamine-producing nerve cells in the brain. The reason behind the cell death is still unclear, but abnormal build-up of the protein alpha-synuclein (AS) in the brain is known to occur in patients with some neurodegenerative diseases, including Parkinson's. 'Uncovering why this build-up happens is important to increasing our understanding of Parkinson's and identifying targets for new treatments,' said Kieren Breen, director of research and development at the Parkinson's Disease Society of the UK. 

Recently it has been proposed that intermediate forms of AS, as it converts from the soluble native form into insoluble fibrils, are the main pathogenic species. But these are hard to detect directly and the methods normally used to study fibril formation - circular dichroism and fluorescence - are not able to distinguish the early stages of the process. Now, Emil Palecek from the Academy of Sciences of the Czech Republic in Brno, and colleagues from the Czech Republic and Germany, have developed an electrochemical way of monitoring AS aggregation in vitro. 

The intermediates formed as alpha-synuclein aggregates into insoluble fibrils have been proposed to be pathogenic

Palecek's method relies on AS adsorption at a mercury electrode. Proteins are known to catalyse hydrogen evolution at these electrodes and Palecek's team has used a method called constant current chronopotentiometric stripping to study this hydrogen evolution when catalysed by AS. The technique is remarkably sensitive to local and global changes in protein structure, say the researchers, and it can be used to detect proteins at subnanomolar concentrations.

The destabilisation of the native AS into unfolded monomer followed by aggregation into oligomer, protofibril and finally fibril can be monitored using the technique. 'Our electrochemical determinations reveal previously undetected changes in AS preceding the formation of protofilaments and fibrils,' said Palecek. 

The team suggests its technique could allow a better understanding of intermediate formation in AS build-up. Palecek added that the team's results also offer simple methods for investigating various agents' abilities to affect AS aggregation in vitro. Such studies could lead to effective strategies for preventing and/or treating Parkinson's disease, he said.

Freya Mearns