N-acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation

Sy, Michael; Brandt, Alexander U.; Lee, Sung-Uk; Newton, Barbara L.; Pawling, Judy; Golzar, Autreen; Rahman, Anas M. Abdel; Yu, Zhaoxia; Cooper, Graham; Scheel, Michael; Paul, Friedemann; Dennis, James W.; Demetriou, Michael

doi:10.1074/jbc.ra120.015595

Cited by 32 publications

(38 citation statements)

References 75 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Differentiation of peripheral T cells into pro-inflammatory Th1 and Th17 cells is inhibited by the galectin lattice, which combines with T cell receptor regulation, and determines the risk of autoimmune diseases such as MS (Demetriou et al, 2001;Lee et al, 2007;Grigorian et al, 2011). In addition to immune regulation, the galectin lattice drives myelination by promoting the surface retention of PDGFRα in OPC, a receptor that plays a critical role in oligodendrogenesis (Sy et al, 2020). Mgat5-mediated branching and poly-LacNAc formation depend on GlcNAc availability in cells.…”

Section: Discussionmentioning

confidence: 99%

Galectins and Their Ligand Glycoconjugates in the Central Nervous System Under Physiological and Pathological Conditions

Nio‐Kobayashi

Itabashi

2021

Front. Neuroanat.

View full text Add to dashboard Cite

Galectins are β-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system (CNS) and regulate various physiological and pathological events. This review summarizes the current knowledge of the cellular expression and role of galectins in the CNS, and discusses their functions in neurite outgrowth, myelination, and neural stem/progenitor cell niches, as well as in ischemic/hypoxic/traumatic injuries and neurodegenerative diseases such as multiple sclerosis. Galectins are expressed in both neurons and glial cells. Galectin-1 is mainly expressed in motoneurons, whereas galectin-3-positive neurons are broadly distributed throughout the brain, especially in the hypothalamus, indicating its function in the regulation of homeostasis, stress response, and the endocrine/autonomic system. Astrocytes predominantly contain galectin-1, and galectin-3 and−9 are upregulated along with its activation. Activated, but not resting, microglia contain galectin-3, supporting its phagocytic activity. Galectin-1,−3, and -4 are characteristically expressed during oligodendrocyte differentiation. Galectin-3 from microglia promotes oligodendrocyte differentiation and myelination, while galectin-1 and axonal galectin-4 suppress its differentiation and myelination. Galectin-1- and- 3-positive cells are involved in neural stem cell niche formation in the subventricular zone and hippocampal dentate gyrus, and the migration of newly generated neurons and glial cells to the olfactory bulb or damaged lesions. In neurodegenerative diseases, galectin-1,-8, and -9 have neuroprotective and anti-inflammatory activities. Galectin-3 facilitates pro-inflammatory action; however, it also plays an important role during the recovery period. Several ligand glycoconjugates have been identified so far such as laminin, integrins, neural cell adhesion molecule L1, sulfatide, neuropilin-1/plexinA4 receptor complex, triggering receptor on myeloid cells 2, and T cell immunoglobulin and mucin domain. N-glycan branching on lymphocytes and oligodendroglial progenitors mediated by β1,6-N-acetylglucosaminyltransferase V (Mgat5/GnTV) influences galectin-binding, modulating inflammatory responses and remyelination in neurodegenerative diseases. De-sulfated galactosaminoglycans such as keratan sulfate are potential ligands for galectins, especially galectin-3, regulating neural regeneration. Galectins have multitudinous functions depending on cell type and context as well as post-translational modifications, including oxidization, phosphorylation, S-nitrosylation, and cleavage, but there should be certain rules in the expression patterns of galectins and their ligand glycoconjugates, possibly related to glucose metabolism in cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Galectins and Their Ligand Glycoconjugates in the Central Nervous System Under Physiological and Pathological Conditions

Nio‐Kobayashi

Itabashi

2021

Front. Neuroanat.

View full text Add to dashboard Cite

show abstract

“…Furthermore, NUCB1 was reported as a novel pan-neuronal calcium handling marker, correlated to Alzheimer’s disease [ 45 ]. Unlike those, N-acetyl-D-glucosamine has a neuroprotective role as a regulator of primary myelination and myelin repair and is of importance in demyelinating diseases like multiple sclerosis [ 46 ]. Finally, adenine is, as one of the purines, involved in neuromodulation, neurotransmission, activation of differentiation and neuritogenesis of precursor cells and neurons.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, adenine is, as one of the purines, involved in neuromodulation, neurotransmission, activation of differentiation and neuritogenesis of precursor cells and neurons. Additionally, purines also contribute to immunological response due to astrocytes and microglia activation, initiating the inflammatory reactions [ 46 ]. The diagnostic significance and potential are yet to be examined by further studies.…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Approach to Elucidate Cerebrospinal Fluid Changes in Dogs with Intervertebral Disc Herniation

Horvatić

Gelemanović

Pirkić

et al. 2021

IJMS

View full text Add to dashboard Cite

Herniation of the intervertebral disc (IVDH) is the most common cause of neurological and intervertebral disc degeneration-related diseases. Since the disc starts to degenerate before it can be observed by currently available diagnostic methods, there is an urgent need for novel diagnostic approaches. To identify molecular networks and pathways which may play important roles in intervertebral disc herniation, as well as to reveal the potential features which could be useful for monitoring disease progression and prognosis, multi-omics profiling, including high-resolution liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem mass tag (TMT)-based proteomics was performed. Cerebrospinal fluid of nine dogs with IVDH and six healthy controls were used for the analyses, and an additional five IVDH samples were used for proteomic data validation. Furthermore, multi-omics data were integrated to decipher a complex interaction between individual omics layers, leading to an improved prediction model. Together with metabolic pathways related to amino acids and lipid metabolism and coagulation cascades, our integromics prediction model identified the key features in IVDH, namely the proteins follistatin Like 1 (FSTL1), secretogranin V (SCG5), nucleobindin 1 (NUCB1), calcitonin re-ceptor-stimulating peptide 2 precursor (CRSP2) and the metabolites N-acetyl-D-glucosamine and adenine, involved in neuropathic pain, myelination, and neurotransmission and inflammatory response, respectively. Their clinical application is to be further investigated. The utilization of a novel integrative interdisciplinary approach may provide new opportunities to apply innovative diagnostic and monitoring methods as well as improve treatment strategies and personalized care for patients with degenerative spinal disorders.

show abstract

“…Moreover, proteoglycans such as NG2 are important determinants of OPC migration [ 74 ]. Indeed, it has been reported that N-glycan branching of GlcNAc is important in myelination and myelin repair [ 75 ].…”

Section: Energy Fuels Used By Oligodendrogliamentioning

confidence: 99%

Oligodendroglial Energy Metabolism and (re)Myelination

Tepavčević

2021

Life

View full text Add to dashboard Cite

Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has been evoked as an important contributor to various CNS disorders, including multiple sclerosis (MS). Thus, dysregulation of energy homeostasis in oligodendroglia may be an important contributor to myelin dysfunction and lack of repair observed in the disease. This article will focus on energy metabolism pathways in oligodendroglial cells and highlight differences dependent on the maturation stage of the cell. In addition, it will emphasize that the use of alternative energy sources by oligodendroglia may be required to save glucose for functions that cannot be fulfilled by other metabolites, thus ensuring sufficient energy input for both myelin synthesis and trophic support to the axons. Finally, it will point out that neuropathological findings in a subtype of MS lesions likely reflect defective oligodendroglial energy homeostasis in the disease.

show abstract

N-acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation

Cited by 32 publications

References 75 publications

Galectins and Their Ligand Glycoconjugates in the Central Nervous System Under Physiological and Pathological Conditions

Galectins and Their Ligand Glycoconjugates in the Central Nervous System Under Physiological and Pathological Conditions

Multi-Omics Approach to Elucidate Cerebrospinal Fluid Changes in Dogs with Intervertebral Disc Herniation

Oligodendroglial Energy Metabolism and (re)Myelination

Contact Info

Product

Resources

About