Polysialic Acid in Development
and Disease Processes

Polysialic acid (PSA) is an essential carbohydrate component of cell membranes during brain development and also in cancer formation. It is a linear homopolymer of acetylneuraminic acid -- in other words, a long, unbranched chain of repeating sugar molecules.

PSA attaches to another molecule, usually a neural cell adhesion molecule called NCAM, which is located in the cell membrane of many neural progenitor cells (young nerve cells and neural stem cells) in the central nervous system.

The function of PSA: PSA is generated by enzymes called (poly)sialyltransferases that add neuraminic acid (sugar monomers) to the end of a growing PSA chain. PSA can have up to 200 sugar monomers! So we can imagine, for the purpose of illustration, that a round cell has hundreds of NCAM molecules on its surface, and attached to each of these anchors is a long, wiggly string of PSA, like hair covering the cell.

This way, it's easy to understand that cells with PSA-NCAM will have a harder time interacting with other cells covered with PSA-NCAM. So, among other functions, PSA inhibits the interaction of cells with each other because of the long spikes of PSA holding them apart.

This property has major implications for how expression of PSA on the surface of a cell affects its behavior. Given the fact that cells can rapidly turn the expression of PSA 'ON' or 'OFF', polysialic acid can serve as a versatile regulator of a cell's activities. More on this below...

History of early research on PSA: A search of the scientific literature reveals over 600 articles on PSA, and rapidly counting. Like most areas of scientific research, work on PSA has been full of surprises and fascinating discoveries. To summarize all of this work is beyond the scope of this brief review, but we will try to pick the most interesting highlights.

PSA was first identified in 1979 as surface polymers on the coating of the E. coli bacterium. In the early 1980's, researchers studying bacteria that cause meningitis (inflammation of the membranes surrounding the brain) noticed similarities between molecules on the bacteria and molecules in the brain itself. And, true enough, further experiments revealed the existence of enzymes that synthesize polysialic acid and attach it to NCAM.

The Role of PSA in Brain Development and Regeneration
Because of the versatility of PSA expression on cells, this molecule plays a significant role in many different processes in development. Importantly, very recent research (Glaser et al. Stem Cells, 12/07) indicates that among migrating neural progenitor cells, those expressing high levels of PSA have an enhanced ability to respond to guidance cues in the brain tissue. (To be continued....)

The Role of PSA in Cancer Formation
In cancer, mutations in genes encoding for sialyltransferases that synthesize PSA can contribute to mis-expression of PSA on the surface of cells. As we have seen above in neural development, changes in PSA expression alter a cell's ability to interact with other cells. In cancer that metastasizes and spreads, a lack of cell adhesion and increased mobility is at the heart of cell spreading to other areas. (To be continued...)

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