How Inhibition of Enzyme Leads to the Development of Alzheimer's Analyzed

Researchers have discovered how the blood plasma protein fetuin-B binds to the enzyme meprin β and used a computer model to visualize their findings for understanding more about the Alzheimer's disease.

Meprin β releases proteins from cell membranes, controlling important physiological functions in the human body. But, a dysregulation of this process can trigger the development of Alzheimer's and cancer.

Meprin β is regulated by fetuin-B binding to the enzyme when required, thereby preventing the release of other proteins, as per the findings in the journal "Proceedings of the National Academy of Sciences".

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‘A drug that binds to the enzyme meprin β and inhibits it in same wat like fetuin-could be a new way of treating Alzheimer's.’
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Research team produced meprin β and fetuin-B in insect cells and then allowed them to react with one other in a test tube. Using enzyme kinetics and biophysical analyses, the researchers determined that this reaction resulted in an exceptionally stable, high-molecular-mass complex.

Their colleagues managed to crystallize the complex and determine its three-dimensional structure using X-ray crystallography. This involved X-rays being fired at the protein crystals, which allowed the atomic structure of the crystals to be calculated from the diffraction of the X-rays. A computer model of the structure was then generated.

"Thanks to the model, we can now see exactly how meprin β and fetuin-B bind together," said Professor Walter Stöcker, who conducted the research at JGU together with Dr. Hagen Körschgen and Nele von Wiegen.

"This research represents an excellent starting point for gaining a better understanding of diseases such as Alzheimer's and for developing the drugs to combat them."

Moreover, people with Alzheimer's disease have relatively little fetuin-B in their blood, which in turn may lead to a lack of regulation of meprin β. "If it is possible to develop a drug that binds to the enzyme and inhibits it in a similar way to fetuin-B, this could be a new way of treating Alzheimer's," concluded Stöcker.

Source-Medindia