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The Journal of Neuroscience, October 15, 2002, 22(20):8869-8875

Biochemical Engineering of Cell Surface Sialic Acids Stimulates Axonal Growth

Bettina Büttner^{1, *}, Christoph Kannicht^{2, *}, Carolin Schmidt¹, Klemens Löster², Werner Reutter¹, Hye-Youn Lee¹, Sabine Nöhring¹, and Rüdiger Horstkorte¹

¹ Institut für Molekularbiologie und Biochemie, Fachbereich Humanmedizin, Freie Universität Berlin, D-14195 Berlin-Dahlem, Germany, and ² Octapharma Pharmaceutica, A-1100 Vienna, Austria (Department-Unit for Molecular Biochemistry, D-14195 Berlin-Dahlem, Germany)

Sialylation is essential for development and regeneration in mammals. Using N-propanoylmannosamine, a novel precursor of sialic acid, we were able to incorporate unnatural sialic acids with a prolonged N-acyl side chain (e.g., N-propanoylneuraminic acid) into cell surface glycoconjugates. Here we report that this biochemical engineering of sialic acid leads to a stimulation of neuronal cells. Both PC12 cells and cerebellar neurons showed a significant increase in neurite outgrowth after treatment with this novel sialic acid precursor. Furthermore, also the reestablishment of the perforant pathway was stimulated in brain slices. In addition, we surprisingly identified several cytosolic proteins with regulatory functions, which are differentially expressed after treatment with N-propanoylmannosamine. Because sialic acid is the only monosaccharide that is activated in the nucleus, we hypothesize that transcription could be modulated by the unnatural CMP-N-propanoylneuraminic acid and that sialic acid activation might be a general tool to regulate cellular functions, such as neurite outgrowth.

Key words: N-propanoylmannosamine; neurite outgrowth; regeneration; sialylation; 2D-gel electrophoresis; MALDI-TOF MS

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^* B.B. and C.K. contributed equally to this work.

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22208869-07$05.00/0

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