Glycosylation and behavioral symptoms in neurological disorders

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: May 8, 2023

Abstract Glycosylation, the addition of glycans or carbohydrates to proteins, lipids, other glycans, is a complex post-translational modification that plays crucial role in cellular function. It estimated at least half all mammalian proteins undergo glycosylation, underscoring its importance functioning cells. This reflected fact significant portion human genome, around 2%, devoted encoding enzymes involved glycosylation. Changes glycosylation have been linked various neurological disorders, including Alzheimer’s disease, Parkinson’s autism spectrum disorder, and schizophrenia. Despite widespread occurrence, central nervous system remains largely unknown, particularly with regard impact on behavioral abnormalities brain diseases. review focuses examining three types glycosylation: N-glycosylation, O-glycosylation, O-GlcNAcylation, manifestation symptoms neurodevelopmental, neurodegenerative, neuropsychiatric disorders.

Language: Английский

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An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 4, 2024

Abstract N- glycosylation is an abundant post-translational modification of most cell-surface proteins. glycans play a crucial role in cellular functions like protein folding, localization, cell–cell signaling, and immune detection. As different tissue types display glycan profiles, changes compositions occur tissue-specific ways with development disease, cancer. However, no comparative atlas resource exists for documenting glycome alterations across various human types, particularly comparing normal cancerous tissues. In order to study broad range N -glycomes, -glycan targeted MALDI imaging mass spectrometry was applied custom formalin-fixed paraffin-embedded microarrays. These encompassed fifteen including bladder, breast, cervix, colon, esophagus, gastric, kidney, liver, lung, pancreas, prostate, sarcoma, skin, thyroid, uterus. Each array contained both tumor cores from the same pathology block, selected by pathologist, allowing more in-depth comparisons differences between types. Using established MALDI-IMS workflows existing databases, present each core were spatially profiled peak intensity data compiled analyses. Further structural information determined fucosylation using endoglycosidase F3, differentiation sialic acid linkages through stabilization chemistry. Glycan compared oligomannose levels, branching complexity, presence bisecting acetylglucosamine, fucosylation, sialylation. Collectively, our research identified that significantly increased and/or decreased relative abundance cancer type. This offers valuable on wide scale tissues, serving as reference future studies potential diagnostic applications MALDI-IMS.

Language: Английский

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Transcriptomic and glycomic analyses highlight pathway-specific glycosylation alterations unique to Alzheimer’s disease

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: May 15, 2023

Glycosylation has been found to be altered in the brains of individuals with Alzheimer's disease (AD). However, it is unknown which specific glycosylation-related pathways are AD dementia. Using publicly available RNA-seq datasets covering seven brain regions and including 1724 samples, we identified genes ubiquitously changed AD. Several differentially expressed glycosyltransferases by were confirmed qPCR a different set human medial temporal cortex (MTC) samples (n = 20 vs. controls). N-glycan-related changes predicted expression these mass spectrometry (MS)-based N-glycan analysis MTC 9 6 About 80% at least one region participants (adjusted p-values < 0.05). Upregulation MGAT1 B4GALT1 involved complex N-linked glycan formation galactosylation, respectively, reflected increased concentrations corresponding N-glycans. Isozyme-specific observed polypeptide N-acetylgalactosaminyltransferase (GALNT) family alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (ST6GALNAC) enzymes. glycolipid-specific (UGT8, PIGM) upregulated. The critical transcription factors regulating N-glycosylation elongation include STAT1 HSF5. miRNA has-miR-1-3p has-miR-16-5p, respectively. Our findings provide an overview glycosylation affected potential regulators glycosyltransferase that deserve further validation suggest occurring dementia highly pathway-specific unique

Language: Английский

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Structure and evolution of neuronal wiring receptors and ligands

Developmental Dynamics, Journal Year: 2022, Volume and Issue: 252(1), P. 27 - 60

Published: June 21, 2022

One of the fundamental properties a neuronal circuit is map its connections. The cellular and developmental processes that allow for growth axons dendrites, selection synaptic targets, formation functional synapses use surface receptors their interactions with other receptors, secreted ligands, matrix molecules. Spatiotemporal regulation expression these cues allows specificity in pathways wire stereotyped circuits. families molecules controlling axon guidance synapse are generally conserved across animals, some important exceptions, which have consequences connectivity. Here, we summarize distribution such multiple taxa, focus on model organisms, evolutionary led to multitude molecules, diversification or loss receptors.

Language: Английский

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Human-specific features and developmental dynamics of the brain N-glycome

Science Advances, Journal Year: 2023, Volume and Issue: 9(49)

Published: Dec. 6, 2023

Comparative "omics" studies have revealed unique aspects of human neurobiology, yet an evolutionary perspective the brain N-glycome is lacking. We performed multiregional characterization rat, macaque, chimpanzee, and N-glycomes using chromatography mass spectrometry then integrated these data with complementary glycotranscriptomic data. found that, in primates, has diverged more rapidly than underlying transcriptomic framework, providing a means for generating additional interspecies diversity. Our suggest that evolution hominids been characterized by overall increase complexity coupled shift toward increased usage α(2-6)-linked N-acetylneuraminic acid. Moreover, differences cell type expression pattern key glycogenes were identified, including some human-specific differences, which may underpin this divergence. Last, comparing prenatal adult N-glycomes, we uncovered region-specific neurodevelopmental pathways lead to distinct spatial N-glycosylation profiles mature brain.

Language: Английский

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New Avenues for Human Blood Plasma Biomarker Discovery via Improved In-Depth Analysis of the Low-Abundant N–glycoproteome

Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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N-glycosylation of ACTRIIB enhances protein stability leading to rapid cell proliferation and strong resistance to docetaxel in nasopharyngeal carcinoma

Brazilian Journal of Medical and Biological Research, Journal Year: 2025, Volume and Issue: 58

Published: Jan. 1, 2025

Nasopharyngeal carcinoma (NPC) is a malignant tumor predominantly influenced by Epstein-Barr virus infection and genetic factors. The transforming growth factor-beta (TGF-β) superfamily implicated in various cellular processes, including tumorigenesis. This study aimed to detect the role of one TGF-β member activin receptor type IIB (ACTRIIB) NPC. analyzed NPC datasets, GSE12452, GSE102349, GSE53819. ACTRIIB expression N-glycosylation levels were assessed western blot, real-time PCR, immunofluorescence, immunohistochemistry cells tissues. As indicated was significantly upregulated tissues, up-regulation associated with poor prognosis. confirmed primarily at forty-second amino acid, an asparagine. promoted localization cell membrane prevented degradation protein lysosomes, through which activated downstream Smard1/2 promote proliferation invasion. Inhibition or knockdown resulted reduced invasion increased sensitivity docetaxel. In conclusion, critical post-translational modification that enhanced stability induced localization, facilitates functions could potentially serve as therapeutic strategy improve efficacy chemotherapy

Language: Английский

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Distinct spatial N‐glycan profiles reveal glioblastoma‐specific signatures

The Journal of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Abstract This study explored the complex interactions between glycosylation patterns, tumour biology, and therapeutic responses to temozolomide (TMZ) in human malignant glioma, specifically CNS WHO grade 3 oligodendroglioma (ODG) glioblastoma (GB). Using spatial imaging of N‐glycans formalin‐fixed paraffin‐embedded (FFPE) tissue sections via MALDI‐MSI, we analysed N‐glycome primary recurrent GB tissues orthotopic xenografts patient‐derived brain tumour‐initiating cells (BTIC) sensitive or resistant TMZ. We identified unique N‐glycosylation profiles, with nontumor (NTB) ODG showing higher levels bisecting tri‐antennary structures, while exhibited more tetra‐antennary sialylated N‐glycans. Distinctive sialylation patterns were observed, specific α2,6 α2,3 isomeric linkages significantly altered GB. Moreover, comparative analysis revealed elevated high mannose fucosylated bi‐ tissues. Next, TMZ‐sensitive TMZ‐resistant patient initiating (BTIC), potential N‐glycan markers for TMZ treatment response resistance. Finally, found expression genes involved biosynthesis highlighting crucial role glioma therapy lays foundation developing glycosylation‐based diagnostic biomarkers targeted therapies, potentially improving clinical outcomes patients. © 2025 The Pathological Society Great Britain Ireland.

Language: Английский

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Heterogeneities of Site-Specific N-Glycosylation in the Hippocampus of Depression-like Behavior Models in Mice Induced by Acute Stress and Chronic Stress

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

It is well established that acute and chronic stress contributes to the onset progression of depression, but underlying mechanisms have not been elucidated. Here an integrated N-glycoproteomic proteomic analysis was performed investigate heterogeneities glycoprotein site-specific glycosylation between hippocampi control, stress-affected (AS), mild (CMS) mice. 1063 unique intact N-glycopeptides, 116 N-glycan compositions, 512 sites were identified. CMS AS had significant effects on glycosylation. reduced multiantenna (N8H8 N6H5F1S1) more strongly, while (N5H3F1) strongly. inhibited high-mannose synthesis with high polymerization (N2H9 N2H8), low (N2H6, H2H5). Furthermore, 26 39 glycosylation-related genes (GRGs) identified in groups, separately. Functional enrichment for GRGs groups exhibited up-regulated functions leading edge membrane cell adhesion molecule binding; meanwhile, down-regulated cAMP signaling pathways. Finally, tSNE based ScRNA-seq revealed core highly expressed astrocytes. All these findings improve our understanding stress-related providing valuable data resources depression pathogenesis exploration novel therapeutic target discovery.

Language: Английский

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O-GalNAc glycans are enriched in neuronal tracts and regulate nodes of Ranvier

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(9)

Published: Feb. 25, 2025

Protein O-glycosylation is a critical modification in the brain, as genetic variants pathway are associated with common and severe neuropsychiatric phenotypes. However, little known about most abundant O-glycans mammalian which N-acetylgalactosamine (O-GalNAc) linked. Here, we determined spatial localization, protein carriers, cellular function of O-GalNAc glycans mouse brain. We observed striking enrichment neuronal tracts, specifically at nodes Ranvier, specialized structures involved signal propagation Glycoproteomic analysis revealed that more than half identified were present on chondroitin sulfate proteoglycans termed lecticans, display both domain regional heterogeneity. Inhibition synthesis neurons reduced binding Siglec-4, regulator neurite growth, shortened length Ranvier. This work establishes brain will inform future studies their role development disease.

Language: Английский

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