Neurobiology of N-glycosylation modification and its roles in neurological disorders

doi:10.16098/j.issn.0529-1356.2024.02.017

Abstract

Abstract:

Neurodevelopment and neuronal function are modulated by multiple factors including environment, genetics and epigenetics. As a post-translational modification, N-glycosylation is catalyzed by glycosyltransferase and involves in diverse biological processes. N-glycosylation is abundant in neuronal system, regulates the development and maturation of synapse, and inflammatory response of glial cells. The dysregulation of N-glycosylation induces neurological disorders including Alzheimer’s disease, congenital disorders of glycosylation, schizophrenia and epilepsy. In the present review, we have summarized the progresses of N-glycosylation in regulating neuronal and astrocytic function, and its roles in neurological disorders and related mechanisms.

Key words: N-glycan, N-glycosylation, Neuron, Glia, Neuronal development, Neurological disorder

CLC Number:

XU Ke-xing WANG Meng-xuan LI Xue-kun. Neurobiology of N-glycosylation modification and its roles in neurological disorders[J]. Acta Anatomica Sinica, 2024, 55(2): 241-246.

References

［1］Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease ［J］. Cell, 2006, 126 (5): 855-867.

［2］Reily C, Stewart TJ, Renfrow MB, et al. Glycosylation in health and disease ［J］. Nat Rev Nephrol, 2019, 15 (6): 346-366.

［3］Schwarz F, Aebi M. Mechanisms and principles of N-linked protein glycosylation ［J］. Curr Opin Struct Biol, 2011, 21 (5): 576-582.

［4］Esmail S, Manolson MF. Advances in understanding N-glycosylation structure, function, and reg ulation in health and disease ［J］. Eur J Cell Biol, 2021, 100 (7-8): 151186.

［5］Ng BG, Freeze HH. Perspectives on Glycosylation and Its Congenital Disorders ［J］. Trends in Genetics, 2018, 34 (6): 466-476.

［6］Paprocka J, Jezela-Stanek A, Tylki-Szymanska A, et al. Congenital Disorders of Glycosylation from a Neurological Perspective ［J］. Brain Sci, 2021, 11 (1): 88.

［7］Freeze HH, Eklund EA, Ng BG, et al. Neurological aspects of human glycosylation disorders ［J］. Annu Rev Neurosci, 2015, 38 105-125.

［8］Klaric TS, Lauc G. The dynamic brain N-glycome ［J］. Glycoconjugate J, 2022, 39 (3): 443-471.

［9］Conroy LR, Hawkinson TR, Young LEA, et al. Emerging roles of N-linked glycosylation in brain physiology and disorders ［J］. Trends Endocrinol Metab J, 2021, 32 (12): 980-993.

［10］Liu H, Xing AF, Liu GZh, et al. Changes of RAGE and LRP-1in the cortex and hippocampus of rats with chronic cerebral hypoperfusion［J］. Acta Anatomica Sinica, 2009, 40(2): 204-210. (in Chinese)

刘宏, 邢安凤, 刘国贞, 等. 晚期糖基化终产物受体和低密度脂蛋白受体相关蛋白在慢性脑血流低灌注大鼠皮层和海马的改变［J］. 解剖学报, 2009, 40 (2): 204-210.

［11］Lee J, Ha S, Kim M, et al. Spatial and temporal diversity of glycome expression in mammalian brain ［J］. Proc Natl Acad Sci USA, 2020, 117 (46): 28743-28753.

［12］Yagi H, Kato K. Functional roles of glycoconjugates in the maintenance of stemness and differentiation process of neural stem cells ［J］. Glycoconj J, 2017, 34 (6): 757-763.

［13］Yale AR, Kim E, Gutierrez B, et al. Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation ［J］. Stem cell Rep, 2023, 18 (6): 1340-1354.

［14］Krocher T, Rockle I, Diederichs U, et al. A crucial role for polysialic acid in developmental interneuron migration and the establishment of interneuron densities in the mouse prefrontal cortex ［J］. Development, 2014, 141 (15): 3022-3032.

［15］Bradberry MM, Peters-Clarke TM, Shishkova E, et al. N-glycoproteomics of brain synapses and synaptic vesicles ［J］. Cell Rep, 2023, 42 (4): 112368.

［16］Scott H, Panin VM. N-glycosylation in regulation of the nervous system ［J］. Adv Neurobiol, 2014, 9: 367-394.

［17］Stout KA, Dunn AR, Hoffman C, et al. The synaptic vesicle glycoprotein 2: structure, function, and disease relevance ［J］. ACS Chem Neurosci, 2019, 10 (9): 3927-3938.

［18］Govind AP, Jeyifous O, Russell TA, et al. Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome ［J］. Elife, 2021, 10: e68910.

［19］Issa FA, Hall MK, Hatchett CJ, et al. Compromised N-glycosylation processing of Kv3.1b correlates with perturbed motor neuron structure and locomotor activity ［J］. Biology(Basel), 2021, 10 (6): 486.

［20］Park DH, Park S, Song JM, et al. N-linked glycosylation of the mGlu7 receptor regulates the forward trafficking and transsynaptic interaction with Elfn1 ［J］. FASEB J, 2020, 34 (11): 14977-14996.

［21］Kandel MB, Yamamoto S, Midorikawa R, et al. N-glycosylation of the AMPA-type glutamate receptor regulates cell surface expression and tetramer formation affecting channel function ［J］. J Neurochem, 2018, 147 (6): 730-747.

［22］Inaba H, Kai D, Kida S. N-glycosylation in the hippocampus is required for the consolidation and reconsolidation of contextual fear memory ［J］. Neurobiol Learn Mem, 2016, 135: 57-65.

［23］Chen X, Dang X, Song J, et al. N-glycosylation of Siglec-15 decreases its lysosome-dependent degradation and promotes its transportation to the cell membrane ［J］. Biochem Biophys Res Commum, 2020, 533 (1): 77-82.

［24］Rebelo AL, Gubinelli F, Roost P, et al. Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain ［J］. J Neuroinflammation, 2021, 18 (1): 116.

［25］Zhang Q, Ma C, Chin LS, et al. Integrative glycoproteomics reveals protein N-glycosylation aberrations and glycoproteomic network alterations in Alzheimer’s disease ［J］. Sci Adv, 2020, 6 (40): eabc5802.

［26］Boix CP, Lopez-Font I, Cuchillo-Ibaez I, et al. Amyloid precursor protein glycosylation is altered in the brain of patients with Alzheimer’s disease ［J］. Alzheimers Res Ther, 2020, 12 (1): 96.

［27］Wang W, Gopal S, Pocock R, et al. Glycan mimetics from natural products: new therapeutic opportunities for neurodegenerative disease ［J］. Molecules, 2019, 24 (24): 4604.

［28］Tsatsanis A, Dickens S, Kwok JCF, et al. Post translational modulation of beta-amyloid precursor protein trafficking to the cell surface alters neuronal iron homeostasis ［J］. Neurochem Res, 2019, 44 (6): 1367-1374.

［29］Wang X, Zhou X, Li G, et al. Modifications and trafficking of APP in the pathogenesis of alzheimer’s disease ［J］. Front Mol Neurosci, 2017, 10: 294.

［30］Losev Y, Frenkel-Pinter M, Abu-Hussien M, et al. Differential effects of putative N-glycosylation sites in human Tau on Alzheimer’s disease-related neurodegeneration ［J］. Cell Mol Life Sci, 2021, 78 (5): 2231-2245.

［31］Chan B, Clasquin M, Smolen GA, et al. A mouse model of a human congenital disorder of glycosylation caused by loss of PMM2 ［J］. Hum Mol Genet, 2016, 25 (11): 2182-2193.

［32］Tucholski J, Simmons MS, Pinner AL, et al. N-linked glycosylation of cortical N-methyl-D-aspartate and kainate receptor subunits in schizophrenia ［J］. Neuroreport, 2013, 24 (12): 688-691.

［33］Tucholski J, Simmons MS, Pinner AL, et al. Abnormal N-linked glycosylation of cortical AMPA receptor subunits in schizophrenia ［J］. Schizophrenia Res, 2013, 146 (1-3): 177-183.

［34］Mueller TM, Remedies CE, Haroutunian V, et al. Abnormal subcellular localization of GABAA receptor subunits in schizophrenia brain ［J］. Transl Psychiatry, 2015, 5 (8): e612.

［35］Ezeji JC, Sarikonda DK, Hopperton A, et al. Parabacteroides distasonis: intriguing aerotolerant gut anaerobe with emerging antimicrobial resistance and pathogenic and probiotic roles in human health ［J］. Gut Microbes, 2021, 13 (1): 1922241.

［36］Kang JQ. Epileptic mechanisms shared by alzheimer’s disease: viewed via the unique lens of genetic epilepsy ［J］. Int J Mol Sci, 2021, 22 (13): 7133.

［37］Witters P, Tahata S, Barone R, et al. Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG ［J］. Genet Med, 2020, 22 (6): 1102-1107.

［38］Sim NS, Seo Y, Lim JS, et al. Brain somatic mutations in SLC35A2 cause intractable epilepsy with aberrant N-glycosylation ［J］. Neurol Genet, 2018, 4 (6): e294.

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