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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Clinical and biochemical footprints of congenital disorders of glycosylation: Proposed nosology

Molecular Genetics and Metabolism, Journal Year: 2024, Volume and Issue: 142(1), P. 108476 - 108476

Published: April 10, 2024

We have identified 200 congenital disorders of glycosylation (CDG) caused by 189 different gene defects and proposed a classification system for CDG based on the mode action. This includes 8 categories: 1. Disorders monosaccharide synthesis interconversion, 2. nucleotide sugar transport, 3. N-linked protein glycosylation, 4. O-linked 5. lipid 6. vesicular trafficking, 7. multiple pathways 8. glycoprotein/glycan degradation. Additionally, using information from IEMbase, we described clinical involvement 19 organs systems, as well essential laboratory investigations each type CDG. Neurological, dysmorphic, skeletal, ocular manifestations were most prevalent, occurring in 81%, 56%, 53%, 46% CDG, respectively. was followed digestive, cardiovascular, dermatological, endocrine, hematological symptoms (17-34%). Immunological, genitourinary, respiratory, psychiatric, renal less frequently reported (8-12%), with hair dental abnormalities present only 4-7% The provided this study, including our may be beneficial healthcare providers caring individuals metabolic conditions associated

Language: Английский

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Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 13, 2023

Abstract Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application high-dimensionality reduction/spatial clustering and histopathological annotation matrix datasets to assess tissue metabolic heterogeneity in human lung diseases. Using features identified from this pipeline, hypothesize that channeling between glycogen N-linked glycans critical process favoring pulmonary fibrosis progression. To test hypothesis, induced two different mouse models with lysosomal utilization deficiency. Both displayed blunted glycan levels nearly 90% reduction endpoint when compared WT animals. Collectively, provide conclusive evidence required In summary, study provides roadmap leverage metabolomics understand foundational biology

Language: Английский

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Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Abstract BACKGROUND Synaptic and extrasynaptic distribution of N‐methyl‐D‐aspartate receptors (NMDARs) has not been addressed in the brain from Alzheimer´s disease (AD) subjects, despite their contribution to neurodegeneration. METHODS We have developed a protocol isolate synaptic membranes controls AD frontal cortex. characterized NMDAR subunits GluN2B, GluN2A, GluN1, GluN3A, as well post‐translational modifications, such phosphorylation glycosylation. RESULTS Lower levels GluN2B GluN2A were found fractions, while GluN1 significantly higher; GluN3A remained unaffected AD. also identified different glycoforms membranes. Tyr1472 was lower fractions. DISCUSSION Reduction subunits, particularly for is likely contribute transmission failure Additionally, increment could favor activation excitotoxicity Highlights New human Low High Specific GluN2A. at

Language: Английский

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The dynamic brain N-glycome

Glycoconjugate Journal, Journal Year: 2022, Volume and Issue: 39(3), P. 443 - 471

Published: March 25, 2022

Language: Английский

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Recommendations for reproducibility of cerebrospinal fluid extracellular vesicle studies

Journal of Extracellular Vesicles, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 29, 2023

Cerebrospinal fluid (CSF) is a clear, transparent derived from blood plasma that protects the brain and spinal cord against mechanical shock, provides buoyancy, clears metabolic waste transports extracellular components to remote sites in brain. Given its contact with cord, CSF most informative biofluid for studies of central nervous system (CNS). In addition other components, contains vesicles (EVs) carry bioactive cargoes (e.g., lipids, nucleic acids, proteins), can have biological functions within beyond CNS. Thus, EVs likely serve as both mediators contributors communication Accordingly, their potential biomarkers CNS diseases has stimulated much excitement attention EV research. However, on present unique challenges relative biofluids, including invasive nature collection, limited volumes low numbers compared plasma. Here, objectives International Society Extracellular Vesicles Task Force are promote reproducibility by providing current reporting best practices, recommendations guidelines, studies. To accomplish this, we created distributed world-wide survey ISEV members assess methods considered 'best practices' EVs, then performed detailed literature review publications was used curate resources. Based responses curated information publications, herein guidelines seven domains: (i) Collection, Processing, Storage; (ii) Separation/Concentration; (iii) Size Number Measurements; (iv) Protein Studies; (v) RNA (vi) Omics Studies (vii) Functional Studies.

Language: Английский

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N-Glycosylation as a Modulator of Protein Conformation and Assembly in Disease

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 282 - 282

Published: Feb. 27, 2024

Glycosylation, a prevalent post-translational modification, plays pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital infections, and inflammation. This review delves into the interplay between protein conformation, with specific focus on profound impact N-glycans selection distinct conformations characterized interactomes—namely, assemblies—under normal pathological conditions across various diseases. We begin examining spike SARS virus, illustrating how regulate infectivity pathogenic agents. Subsequently, we utilize prion chaperone glucose-regulated 94 as examples, exploring instances where N-glycosylation transforms physiological structures disease-associated forms. Unraveling these connections provides valuable insights potential therapeutic avenues deeper comprehension molecular intricacies that underlie disease conditions. exploration glycosylation’s influence conformation effectively bridges gap glycome disease, offering comprehensive perspective implications targeting conformational mutants their pathologic assemblies The goal unravel nuances modifications, shedding light they contribute assembly, disease.

Language: Английский

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Protein glycosylation and glycoinformatics for novel biomarker discovery in neurodegenerative diseases

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 89, P. 101991 - 101991

Published: June 21, 2023

Glycosylation is a common post-translational modification of brain proteins including cell surface adhesion molecules, synaptic proteins, receptors and channels, as well intracellular with implications in development functions. Using advanced state-of-the-art glycomics glycoproteomics technologies conjunction glycoinformatics resources, characteristic glycosylation profiles tissues are increasingly reported the literature growing evidence shows deregulation central nervous system disorders, aging associated neurodegenerative diseases. Glycan signatures tissue also frequently described cerebrospinal fluid due to its enrichment brain-derived molecules. A detailed structural analysis glycans collected publications healthy conditions was undertaken data compiled create browsable dedicated set GlyConnect database glycoproteins (https://glyconnect.expasy.org/brain). The shared molecular composition enhances likelihood novel glycobiomarker discovery for neurodegeneration, which may aid unveiling disease mechanisms, therefore, providing therapeutic targets diagnostic progression monitoring tools.

Language: Английский

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The multifaceted roles of the brain glycogen

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: 168(5), P. 728 - 743

Published: Aug. 9, 2023

Abstract Glycogen is a biologically essential macromolecule that directly involved in multiple human diseases. While its primary role carbohydrate storage and energy metabolism the liver muscle well characterized, recent research has highlighted critical metabolic non‐metabolic roles for glycogen brain. In this review, emerging of homeostasis healthy diseased brain are discussed with focus on advancing our understanding Innovative technologies have led to novel insights into functions detailed. Key how cellular localization impacts neuronal glial function discussed. Perturbed observed disorders brain, including where it serves as disease driver category neurological diseases (n‐GSDs). n‐GSDs include Lafora (LD), adult polyglucosan body (APBD), Cori disease, Glucose transporter type 1 deficiency syndrome (G1D), GSD0b, late‐onset Pompe (PD). They neurogenetic characterized by aberrant which results devastating systemic symptoms. most severe cases, rapid neurodegeneration coupled dementia death soon after diagnosis. Finally, we discuss current treatment strategies currently being developed potential be great benefit patients n‐GSD. Taken together, biological resulted renaissance dramatically advanced both biology disease. Future studies needed expand multifaceted effectively apply these image

Language: Английский

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