Researchers link sugar-studded protein to Alzheimer’s disease

Journal of Biological Chemistry (2022). DOI: 10.1016 / j.jbc.2022.101960 “width =” 358 “height =” 530 “/>

The single glycoform of RPTPζ carries CD33 and Siglec-8 ligands. Yes, the exact proportions of human embryonic stem cells total protein extracted from four donors (numbers) were dissolved on the basis of agarose-acrylamide gels and polished to PVDF. The scaffolds (upper panels) were checked twice with CD33-Fc (red) and anti-RPTPζ (green) and repeated staining (lower panels) with Siglec-8-Fc (red) and anti-RPTPζ ( pound). B, the human aggregate is removed (not shown) and the purification is similar to that of Figure 3. The sampling samples from the binding were resolved on the basis of agarose-acrylamide gels, brushes to PVDF, and two titles. with Siglec-8-Fc (red) and anti-RPTPζ (green) or with CD33-Fc (red) and anti-RPTPζ (green) as shown. Methods: (1) immunization; (2) prefabricated on IgG beads; (3) run through (not tied) Siglec-8-Fc beads; (4-7) a little salt to wash; and (8-10) high salt elutions. Gel-labels contain traces of normal molecular weight that can only be seen in green images. IgG, immunoglobulin G; PVDF, polyvinylidene fluoride; RPTPζ, tyrosine phosphatase zeta receptor protein; Siglec, sialic acid-type lectin immunoglobulin. Credit: Journal of Biology (2022). DOI: 10.1016 / j.jbc.2022.101960

In a reverse engineering study using brain tissue from five people who died of Alzheimer’s disease, researchers Johns Hopkins said they found that specific diabetes mellitus could play a significant role in the development of Alzheimer’s disease. . If further research confirms the findings, the molecule, also known as glycan, could be a new target for early clinical trials, treatment and possibly Alzheimer’s disease, the researchers said.

The survey was published online April 20 in Journal of Biology.

Alzheimer’s disease is the most common form of dementia in the United States. It affects an estimated 5.8 million Americans, with no progress being made at the moment nerve cells in the brain they die because of the accumulation of harmful chemicals called amyloid and tau.

Cleansing the amyloid and tau forms that cause infections is a brain function antibiotics, called microglia. Previous research has found that when cleansing is impaired, Alzheimer’s disease can occur. In some people, this is caused by a proliferation of a receptor on microglia, called CD33.

“Recipients do not work on their own. Something needs to work with them to block microglia from clearing these toxic chemicals in the brain,” said Ronald Schnaar, Ph.D., Professor John Jacob Abel Professor of Pharmacology at Jami University Johns Hopkins, a medical doctor and laboratory director who led the study.

Previous research by researchers has shown that for CD33, these connectors are unique sugars. Known to glycans, these bacteria surround the cell with specialized proteins that help them find the right receptors. Protein –glycan combination is called a glycoprotein.

In an effort to find out which specific glycoprotein is associated with CD33, the Schnaar research team found brain tumors in five people who died of Alzheimer’s disease and five people who died of other causes from the Johns Hopkins Alzheimer’s Center. Of the thousands of glycoproteins collected from tissues, only one is associated with CD33.

To unravel this glycoprotein secret, researchers first needed to separate it from other brain glycoproteins. Since it is the only part of the brain that attaches itself to the CD33, they use this feature to “capture” it and share it.

Glycans contain a variety of building blocks of sugar that have an effect on bacterial interactions. Such sugars can be detected by their components. The researchers used chemical materials to break down the glycan step by step, laying out the origin and structure of its building blocks. The researchers identified the glycan component of glycoprotein as sialylated keratan sulfate.

Afterwards, the researchers identified the exact component of the protein by taking a “fingerprint” using spectroscopy, which detects protein blocks. By comparing the protein molecule of a protein with a description of known protein molecules, the research team was able to decompose the protein component of glycoprotein’s receptor tyrosine phosphatase (RPTP) zeta.

The researchers named the system glycoprotein RPTP zeta S3L.

The group previously received the same “signature” glycan on a protein which regulates the immune response in the airway, and the breakdown of glycan suppresses the immune response in mice.

“We suspect glycan exposure to RPTP zate may play a similar role in killing microglia through CD33,” said Anabel Gonzalez-Gil Alvarenga, Ph.D., a graduate student in the Schnaar Laboratory and the first author of the study.

Further experiments show that brain tissue out of five people who died with Alzheimer’s disease had more than twice as much RPTP zeta S3L than non-contributors. This suggests that this glycoprotein may bind to more CD33 receptors than the healthy brain, limiting it. brainability to purify harmful chemicals.

“The discovery of this unique glycoprotein provides a step towards the discovery of new drugs and the potential for early detection of the disease,” Gonzalez-Gil said.

Subsequently, the researchers planned to further study the RPTP Z3 S3L system to determine how the attached glycans gave the glycoprotein its unique ability to interact with CD33.

How protein in your brain can protect against Alzheimer’s disease

Learn more:
Anabel Gonzalez-Gil et al, Sialoglycan ligand for CD33, Siglec inhibitory microglial factor in Alzheimer’s disease, Journal of Biology (2022). DOI: 10.1016 / j.jbc.2022.101960

hintResearchers have linked diabetes mellitus to Alzheimer’s disease (2022, May 27) and recovered on May 27, 2022 from protein-alzheimer-disease.html

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Researchers link sugar-studded protein to Alzheimer’s disease Source link Researchers link sugar-studded protein to Alzheimer’s disease

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