THE HEALTH | JULY-AUGUST , 2022

BRAIN BITES

BY DR WAEL MY MOHAMED

Consuming the proper proportion of both ( together with protein ) in your daily diet is necessary . The most significant issue is the processing of both fat and sugar .

Is refined sugar your ally or adversary ?

Researchers at Johns Hopkins Medicine determined that a specific sugar molecule may play a crucial role in the development of Alzheimer ’ s disease through a “ reverse engineering ” study utilising brain tissue from five Alzheimer ’ s patients who died . According to the researchers , if more study validates the discovery , the molecule known as a glycan might serve as a new target for early diagnostic testing , therapies , and perhaps even prevention of Alzheimer ’ s disease . The research was published online in the Journal of Biological Chemistry on April 20 , 2022 .

In the United States , Alzheimer ’ s disease is the most prevalent form of dementia . This degenerative condition affects an estimated 5.8 million Americans and is characterised by the death of nerve cells in the brain owing to the accumulation of amyloid and tau .

The brain ’ s immune cells , termed microglia , are responsible for eliminating disease-causing types of amyloid and tau . Alzheimer ’ s disease is more likely to arise when sanitation is subpar . This is induced in some individuals by an excess of the CD33 receptor on microglia cells .

Receptors are not autonomously active . Something must interact with them to prevent microglia from removing these hazardous proteins from the brain .

According to previous studies , these “ connection ” molecules for CD33 are unique sugars . These molecules , known to scientists as glycans , are transported throughout the cell by specialised proteins that assist them in locating their respective receptors . The combination of protein and glycan is known as glycoprotein . To determine which specific glycoprotein interacts with CD33 , researchers from the Johns Hopkins Alzheimer ’ s Disease Research Centre acquired brain tissue from five Alzheimer ’ s disease patients and five individuals who died of other

reasons . Only one of the hundreds of glycoproteins extracted from brain tissue was associated with CD33 .

Before the researchers could identify this unknown glycoprotein , they had to isolate it from the other brain glycoproteins . Since it was the only virus in the brain to connect to CD33 , this property was exploited to “ capture ” and isolate it .

Mass spectroscopy to detect protein-building pieces

Glycans are diverse sugar building blocks that alter the molecule ’ s interactions . These sugars can be distinguished by their constituents .

The researchers employed chemical instruments to dismantle the glycan to identify and arrange its constituent building pieces . The researchers identified the glycan part of the glycoprotein as sialylated keratan sulfate . The researchers then identified the protein component by employing mass spectroscopy , which detects protein building pieces , to get its “ fingerprint .”

By comparing the protein ’ s molecular structure to a database of known protein structures , the research team determined that the glycoprotein ’ s protein component was receptor tyrosine phosphatase ( RPTP ) zeta . The combined glycoprotein structure has

Dr Wael MY Mohamed is with the Department of Basic Medical Science , Kulliyyah of Medicine , International Islamic University Malaysia ( IIUM ).

Glycans are diverse sugar building blocks that alter the molecule ’ s interactions . These sugars can be distinguished by their constituents . ”

been designated RPTP zeta S3L by the researchers .

The same glycan “ signature ” was previously identified on a protein that regulates allergy reactions in the airway , and disruption of the glycan reduced allergic responses in mice . Researchers believe the glycan signature conveyed by RPTP zeta may have a similar effect in microglia deactivation via CD33 .

Additional investigations revealed that the brain tissue of the five Alzheimer ’ s disease patients contained more than twice as much RPTP zeta S3L as that of the healthy donors .

This suggests that this glycoprotein may interact with a more significant number of CD33 receptors than in a healthy brain , restricting the brain ’ s capacity to remove toxic proteins . Simply put , identifying this unique glycoprotein is a step toward discovering novel therapeutic targets and potential early diagnostics for Alzheimer ’ s disease .

Next , the researchers want to investigate the structure of RPTP zeta S3L to identify how the glycoprotein ’ s associated glycans confer its capacity to bind with CD33 .

As I did , make food work for you rather than against you by drinking your coffee without sugar . — The Health