Monday, January 9, 2012

Protein folding can help us treat many diseases

Proteins are needed for basically all processes during life, and they are created by specialized cellular machinery. Their basic structure composes of a string of amino acids, that are folded into a shape that gives the protein its function. Scientists from Northwestern University have studied how a cell makes proteins fold, and claim their newfound knowledge may help us treat a massive amount of nasty diseases, such as the neurodegenerative diseases Alzheimer's disease, Parkinson's disease and ALS. But also cancer, diabetes type II and cystic fibrosis.

Worms and cells
The scientists basically performed two kinds of studies. One of them focused on the study of genes, while the other one revolved around molecules. The gene study was performed in a small worm called C. elegans, which is often used in genetic research. In addition, the scientists set up a culture of human cells, in which they studied over a million molecular compounds. All of this was done to discover genes and molecules that protect proteins from folding incorrectly, or otherwise damage the cell. Many diseases, such as the aforementioned ones, have an underlying pathology of incorrectly folding proteins, which highlights the relevance of the studies.

About 19,000 genes were tested in C. elegans, and the researchers found that about nine genes had an effect of making proteins 'healthier'. More specifically, they had an effect on various proteins, among them the ones that are impaired in a long list of diseases. The next step is to uncover how these genes interact with each other. This may help us to create a strategy of keeping proteins in good shape to prevent numerous diseases, by adapting the activity of said genes.

From the total of one million studied compounds, the scientists from Northwestern University discovered seven classes of compounds, distinguished by their chemical structure, that are able to function as chaperones for proteins. By protecting proteins, they improve their capability of folding into the correct shape, which prevents the cell from getting damaged. An example is protection against heat, which can disrupt protein structure irreversibly, thus destroying its functional capabilities. Some of the chaperones were found to be highly effective, which makes them interesting as a therapeutic target. When these molecules were administered during animal studies, they seemed to be able to cure diseases. Oddly enough, the scientists did not expand on this.

Protein folding
Even a small deviation in how a protein folds can have dire consequences. When proteins do not fold correctly, you can get something called a prion. Prion diseases are well-known: 'mad cow disease', Creutzfeldt-Jakob disease and Alzheimer's are examples. Prions are proteins that are able to form dangerous aggregates. Additionally, they are able to turn healthy proteins into prions, which gives them an infection-like character.

Both studies combined provide a set of interesting information about a fundamental process in biology. The correct folding of proteins is of the utmost importance, and this set of new information helps us to identify pathways and compounds involved with it. Because so many diseases are, in one way or another, related to the folding of proteins, we may be able to greatly expand our treatment options for a wide variety of diseases, which is what makes the studies by Northwestern University of great interest.

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