Chemical biology news from across RSC Publishing.
Solving the insoluble problem for Parkinson's
20 November 2007
European scientists have developed a simple and cheap way to study protein aggregation in Parkinson's disease.
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.
Link to journal article
Changes in interfacial properties of -synuclein preceding its aggregation
Emil Paleek, Veronika Ostatná, Michal Masaík, Carlos W. Bertoncini and Thomas M. Jovin, Analyst, 2008, 133, 76
Parkinson's Disease Society
Parkinson's Disease Society
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