N-Acetyl Neuraminic Acid or as it is also called, Sialic Acid is a key sugar in brain development especially fetal brains. The sugar is also very anti-inflammatory. Sialic acid arrives at the cells in the form of N-Acetylmannosamine or ManNAc. So, sources of mannose are also sources of sialic acid. ManNAc is the precursor for N-Acetyl Neuraminic Acid (Neu₅Ac). There are a lot of different variations within this family of sugars. This sugar affects the viscosity (thickness and fluidity) of mucous membranes in respiratory, reproductive, and intestinal tracts. It protects against colonization/infection bacteria in respiratory epithelial cells.

Researchers with the Glycomis Center at the University of New Hampshire (UNH) investigated this sugar. Led by immunologist Jeffrey Ravetch of Rockefeller University and reported in the 13 May 2008 edition of the journal, Science, they identified a specific carbohydrate structure conferring anti-inflammatory activity to a glycoprotein antibody. Ravetch stated, “The work revolves around immunoglobulin G (IgG), the most abundant antibody in blood plasma. Intravenous immunoglobulin (IVIG) has trace amounts of this very active material which effectively relieves inflammatory effects of lupus, rheumatoid arthritis, asthma, and other autoimmune diseases…All the Sialic Acid on IVIG was converted to the active linkage that confers anti-inflammatory properties.” Researchers reported that when given to arthritic mice, the engineered IgG was 30 times more effective than the IVIG! It is far more effective than standard of care and much less expensive. But it wasn’t a drug so the research never went anywhere.

The UNH Glycomics Center headed by director and research professor, Vernon Reinhold, was responsible for analyzing the exact structure of Sialic Acid. The center developed tools and protocols using multidimensional mass spectrometry to determine the structure and functional relationships of carbohydrates. Reinhold noted that protein and most chains of molecules in the body are linear. They are relatively easy to sequence. However, the sugars are bush-shaped and tree-like which make them much more challenging!

Besides the work on IgG, the UNH Glycomics Center is working to demystify the carbohydrate connections in cancer contributing to metastatic growth. They were investigating glycans in avian flu where Sialic residues on airway surface tissues serve as doorways for viral entry. In that same 2008 report, Reinhold stated, “Carbohydrates are the glue that pulls things together, the cell surface matrix in which cells communicate and they provide the connections for signal transduction…It’s only been within the last decade that we’ve realized that such structures are critical for all kinds of biological function.  This structure-functional relationship will have a huge impact on our health in respect to immune regulation.”

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