Beyond glycosylation: sialic acid precursors act as signaling molecules and are involved in cellular control of differentiation of PC12 cells

Sialic acids represent a family of 9-carbon acidic amino sugars expressed mainly as terminal monosaccharides on most mammalian glycoconjugates. Sialic acids play an outstanding role during cellular processes, such as development and regeneration, as they are involved in a variety of molecular interactions. Sialic acids are synthesized in the cytosol starting from UDP-N-acetylglucosamine by the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine-kinase (GNE), which is the key enzyme in the biosynthesis of sialic acid that catalyzes the generation of N-acetylmannosamine, which in turn is an intermediate of the sialic acid pathway that represents the natural molecular precursor of all sialic acids. Of increasing interest are the influence of the sialic acid precursor N-acetylmannosamine (or related N-acylmannosamines), GNE, and sialic acids themselves on cellular processes such as proliferation, gene expression, or cell differentiation. Here, we present recent data and review indications that N-acylmannosamines (the direct precursors of all sialic acids) may act as signaling molecules, and that the key enzyme of the sialic acid metabolism is directly involved in the regulation of cell proliferation and cell differentiation.