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

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".

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.

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Source-Medindia