Researchers link sugar-studded protein to Alzheimer's diseas
To find out which specific glycoprotein connects with CD33, research team obtained brain tissue from five people who died of Alzheimer's disease and from five people who died from other causes from the Johns Hopkins Alzheimer's Disease Research Center. Among the many thousands of glycoproteins they gathered from the brain tissues, only one connected to CD33.

To identify this mystery glycoprotein, the researchers first needed to separate it from the other brain glycoproteins. Since it was the only one in the brain that attached itself to CD33, they used this feature to "catch" it and separate it. Glycans are made up of various sugar building blocks that influence the molecule's interactions. Such sugars can be identified by their component parts. The researchers used chemical tools to deconstruct the glycan step by step, laying out the identity and order of its building blocks. The researchers identified the glycan portion of the glycoprotein as sialylated keratan sulfate.

Then, the researchers determined the protein component's identity by taking its "fingerprint" using mass spectroscopy, which identifies protein building blocks. By comparing the molecular makeup of the protein with a database of known protein structures, the research team was able to conclude the protein portion of the glycoprotein was receptor tyrosine phosphatase (RPTP) zeta. The researchers named the combined glycoprotein structure RPTP zeta S3L.

The group had previously found the same glycan "signature" on a protein that controls allergic responses in the airway, and that disrupting the glycan dampened allergic responses in mice. They suspect the glycan signature carried on RPTP zeta may have a similar role in deactivating microglia through CD33.

Source: https://www.sciencedirect.com/science/article/pii/S0021925822004008?via=ihub
Like
Comment
Share