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The dynamic brain N-glycome

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Abstract

The attachment of carbohydrates to other macromolecules, such as proteins or lipids, is an important regulatory mechanism termed glycosylation. One subtype of protein glycosylation is asparagine-linked glycosylation (N-glycosylation) which plays a key role in the development and normal functioning of the vertebrate brain. To better understand the role of N-glycans in neurobiology, it’s imperative we analyse not only the functional roles of individual structures, but also the collective impact of large-scale changes in the brain N-glycome. The systematic study of the brain N-glycome is still in its infancy and data are relatively scarce. Nevertheless, the prevailing view has been that the neuroglycome is inherently restricted with limited capacity for variation. The development of improved methods for N-glycomics analysis of brain tissue has facilitated comprehensive characterisation of the complete brain N-glycome under various experimental conditions on a larger scale. Consequently, accumulating data suggest that it’s more dynamic than previously recognised and that, within a general framework, it has a given capacity to change in response to both intrinsic and extrinsic stimuli. Here, we provide an overview of the many factors that can alter the brain N-glycome, including neurodevelopment, ageing, diet, stress, neuroinflammation, injury, and disease. Given this emerging evidence, we propose that the neuroglycome has a hitherto underappreciated plasticity and we discuss the therapeutic implications of this regarding the possible reversal of pathological changes via interventions. We also briefly review the merits and limitations of N-glycomics as an analytical method before reflecting on some of the outstanding questions in the field.

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The authors did not receive support from any organization for the submitted work.

GL is the founder and owner of Genos Ltd, a private research organization that specializes in high-throughput glycomic analysis and has several patents in this field. TK is an employee of Genos Ltd.

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  1. Genos Glycoscience Research Laboratory, Zagreb, Croatia

    Thomas S. Klarić & Gordan Lauc

  2. Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia

    Gordan Lauc

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TK conceived the idea for the article, performed the literature search, and wrote the manuscript. GL critically revised the work. All authors approved the final version to be published.

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GL is the founder and owner of Genos Ltd, a private research organization that specializes in high-throughput glycomic analysis and has several patents in this field. TK is an employee of Genos Ltd.

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GL is the founder and owner of Genos Ltd, a private research organization that specializes in highthroughput glycomic analysis and has several patents in this field. TK is an employee of Genos Ltd.

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Klarić, T.S., Lauc, G. The dynamic brain N-glycome. Glycoconj J 39, 443–471 (2022). https://doi.org/10.1007/s10719-022-10055-x

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