New Method Promises to Quickly Identify Abnormal Proteins Involved in Alzheimer’s

Researchers developed a new method for capturing proteins implicated in several diseases, including Alzheimer’s. The technique promises to accelerate the identification of altered proteins underlying disease progression (biomarkers).

This knowledge may later translate into new targeted therapeutics.

The study, “A mutant O-GlcNAcase enriches Drosophila developmental regulators,” was published in the journal Nature Chemical Biology.

The mechanisms of disease are often shared through a variety of different syndromes from neurodegenerative disease such as Alzheimer’s, to cancers, metabolic syndromes (type 2 diabetes), and cardiovascular diseases.

Modifications in sugars that compose certain proteins is one such mechanism that is deregulated. The correct identification of these altered proteins is a stepping stone toward our understanding of their role in disease development.

Now, researchers at the University of Bradford in the U.K. and the University of Dundee in Scotland developed a new methodology where altered proteins — those exhibiting a specific modification — are easily trapped. The alteration in question is the addition of a sugar, which then affects the function of the protein. While protein modifications are a normal and necessary process for their correct processing and function, sometimes this procedure goes awry, which may cause detrimental effects to the cell’s functioning and well-being.

Previous methods for identifying and capturing these proteins were inefficient, as the sugar modification was often detached from the protein. Expensive equipment and laborious techniques were necessary for the procedure and for the validation of the findings.

The new method is much more simple and does not required expensive and specialized lab equipment, permitting scientists to more rapidly identify the modified proteins. This will allow the researchers to investigate the proteins’ role in the development of several diseases. In fact, identifying the aberrant proteins will prompt the development of innovative, targeted therapeutics for several diseases.

In the new method, researchers grow a protein with an engineered tail which then specifically grabs the sugar-modified protein. This can then be applied to scenarios of complex protein mixtures, such as those that occur in tissues. Here, with the modified tail, researchers can pull out all proteins that bear the sugar modification and proceed to their isolation from the non-transformed proteins.

“This methodology represents a major step forward. We are now in a position where we can easily trap the proteins we need to target,” Dr. Ritchie Williamson of the University of Bradford, one of the authors of the study, said in a press release.

“If we can do this we can then identify the proteins, which we think may be involved in the disease process. We also have the potential to find biomarkers, especially in younger people, and to probe different diseases,” he said.