Statistical method for faster prognosis of Alzheimer’s and Parkinson’s diseases

Sep 13 2004

A large number of diseases − including Alzheimer’s disease, Parkinson’s disease, and mad cow disease − are the result of proteins that erroneously assume the wrong shape, causing them to stick to each other.

This phenomenon is perceptible, but up to now it has been difficult to predict. Researchers from the Flanders Interuniversity Institute for Biotechnology (VIB) at the Free University of Brussels (VUB), in collaboration with a German research group, have developed TANGO − a statistical method that can predict the susceptibility of proteins to sticking together. Thus, for the first time, TANGO enables the prediction of risky protein alterations that underlie this group of diseases.

All living creatures, including humans, are made up of cells, and the vital functions within these cells are executed by proteins. The hereditary information for the production of proteins − including, among other things, their structure and length − is contained in our genes. But in order to be able to function properly, a protein must also fold itself correctly into its 3-dimensional structure. Sometimes this goes wrong and the proteins stick together, making them toxic and causing diseases like Alzheimer’s.

Until recently, it was always thought that proteins stick together arbitrarily. But now it has become clear that a universal mechanism lies behind this process. Certain structural characteristics in proteins determine their susceptibility to sticking together. Using this information, Joost Schymkowitz and Frederic Rousseau have developed TANGO, a mathematical algorithm that looks at a large amount of data − including alterations of the protein and environmental factors − to indicate the degree of probability that particular proteins will stick together.

TANGO thus opens possibilities for new diagnostic techniques for diseases that are caused by proteins that stick together erroneously. The VIB researchers also expect that TANGO will enable more efficient production of proteins for medical or industrial applications. The yield of these production processes is often low, because the proteins stick to each other and are therefore difficult to purify. With TANGO, one can determine under what conditions the solubility of the therapeutic proteins is large enough to purify them easily.