Advancement in treatment for Alzheimer’s disease and cancer could be on the horizon thanks to a novel investigation of the meprin β enzyme.
Researchers from Johannes Gutenberg University Mainz (JGU) in Germany and the Institute of Molecular Biology of Barcelona in Spain manufactured a computer model to visualise the relationship between how the blood plasma protein fetuin-B binds to the enzyme meprin β – which could potentially aid in the development of treatment for Alzheimer’s disease and cancer.
The function of meprin β
Meprin β is an enzyme responsible for releasing proteins from cell membranes; crucially, it has jurisdiction over many of the human body’s principal physiological functions, meaning that the dysregulation of this process can be the causation of Alzheimer’s and cancer.
Fetuin-B (a liver-derived plasma protein) regulates meprin β by tethering to the enzyme when required, mitigating the release of other proteins.
Investigating the relationship of meprin β and fetuin-B
To analyse the association between meprin β and fetuin-B, the team at JGU generated them in insect cells – observing their reaction in a test tube. Utilising the enzyme kinetics and biophysical analyses methods, they discovered that the reaction resulted in an exceptionally stable, high-molecular-mass complex.
In Barcelona, the partnering research team successfully crystallised the complex, firing x-rays at the protein crystals to determine its three-dimensional structure. This method of x-ray crystallography allowed for the atomic structure of crystals to be calculated from the diffraction of the rays, which was then transferred into a computer model.
Walter Stöcker, Professor at Johannes Gutenberg University, said: “Thanks to the model, we can now see exactly how meprin β and fetuin-B bind together. 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.”
Meprin β is already understood to be influential in forming so-called beta-amyloid plaques – a well known characteristic feature of Alzheimer’s disease. Furthermore, those suffering from the disease demonstrate reasonably low amounts of fetuin-B in their blood, which may cause a lack of regulation of meprin β.
Stöcker added: “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.”