Monday, December 10, 2018

NII Researchers show how to change glycosylation non-invasively in mice brain

NII Researchers show how to change glycosylation non-invasively in mice brain

What are glycoproteins? Proteins that carry carbohydrates covalently attached to side chains of amino acids of proteins.

What is glycosylation? The process by which carbohydrates are attached to proteins, catalyzed by numerous enzymes in cells. These enzymes are known as glycosyl transferases.

Why change glycosylation in living animals? In order to understand the functions of glycosylation we need tools by which one could modulate the levels of glycosylation. Such tools would enable understanding of fundamental roles played by glycosylation in development and disease including central nervous system (CNS) disorders.

How to change or tag glycosylation in living animals? One could achieve this by using synthetic monosaccharides that could fool the natural biosynthetic pathways and metabolism and identifying their incorporation using unique chemical reactions known as bio-orthogonal ligation.

What is so important about changing glycosylation in the brain? In 2004, it was shown that glycosylation of peripheral organs such as heart, kidney, and liver in animals could be modified – However, no modification could be achieved in the brain due to the blood-brain barrier (BBB). In Dec 2016, researchers at NII published a strategy to deliver synthetic monosaccharides to the brain by piggybacking them on neuroactive molecules, such as vitamins and drugs, which are known to cross the BBB via carrier-mediated transport. Using this carbohydrate-neuroactive hybrid
(CNH) strategy, for the first time, NII researchers showed that it is possible to alter glycosylation of glycoproteins in brains of mammals. This might facilitate efforts to glean the intricate and complex processes of brain in normal development including learning and memory as well as in CNS disorders, CNS diseases, and auto-immune diseases.

Where could I learn more about the scientific details of the research?

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