Neural glycomics: the sweet side of nervous system functions

Abstract

The success of investigations on the structure and function of the genome (genomics) has been paralleled by an equally awesome progress in the analysis of protein structure and function (proteomics). We propose that the investigation of carbohydrate structures that go beyond a cell’s metabolism is a rapidly developing frontier in our expanding knowledge on the structure and function of carbohydrates (glycomics). No other functional system appears to be suited as well as the nervous system to study the functions of glycans, which had been originally characterized outside the nervous system. In this review, we describe the multiple studies on the functions of LewisX, the human natural killer cell antigen-1 (HNK-1), as well as oligomannosidic and sialic (neuraminic) acids. We attempt to show the sophistication of these structures in ontogenetic development, synaptic function and plasticity, and recovery from trauma, with a view on neurodegeneration and possibilities to ameliorate deterioration. In view of clinical applications, we emphasize the need for glycomimetic small organic compounds which surpass the usefulness of natural glycans in that they are metabolically more stable, more parsimonious to synthesize or isolate, and more advantageous for therapy, since many of them pass the blood brain barrier and are drug-approved for treatments other than those in the nervous system, thus allowing a more ready access for application in neurological diseases. We describe the isolation of such mimetic compounds using not only Western NIH, but also traditional Chinese medical libraries. With this review, we hope to deepen the interests in this exciting field.

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Funding

This work was supported by a grant from the National Health and Medical Research Council (APP1129869 to V.S.). The Li Kashing Foundation is gratefully acknowledged for support (LD030302 to M.S.).

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Correspondence to Vladimir Sytnyk.

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Sytnyk, V., Leshchyns’ka, I. & Schachner, M. Neural glycomics: the sweet side of nervous system functions. Cell. Mol. Life Sci. 78, 93–116 (2021). https://doi.org/10.1007/s00018-020-03578-9

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Keywords

  • Glycans
  • Neurons
  • Brain
  • Regeneration
  • Synaptic plasticity
  • Glycomimetics