Glycosylation as regulator of human B-cell leukaemias in bone marrow DOI Creative Commons
Nora Heisterkamp

Frontiers in Hematology, Год журнала: 2023, Номер 2

Опубликована: Ноя. 16, 2023

Leukemic B-cells are lodged in the bone marrow [BM], a complex organ composed of many cell types and extracellular matrix. Determining how reciprocal interactions between these components regulated is critical to our understanding factors that allow leukemia cells survive, multiply withstand treatment. All surrounded by glycocalyx, glycan-rich layer high complexity, which regulates such cell-cell cell-matrix interactions. However, structure function glycan biomolecules constitute this have not been explored much detail. Gaps difficult fill due technical limitations as well fact composition BM health, disease aging static. This also applies B-lineage malignancies develop or persist B-cell precursor acute lymphoblastic Multiple Myeloma, effects their In contrast, proteomes transcriptomes different human studied more extensively. A combination technologies now increasingly allows correlations be made expression glycosyltransferases structures lines, could extrapolated RNAseq data from primary cells. Glycopeptide analysis will invaluable providing details specific occupancy on glycoproteins, even if only snapshot time. Functional studies CD19, CD138/SDC1 BCMA/TNFRSF17 already demonstrated importance glycosylation. Additional using approaches likely find other instances malignant homeostasis glycosylation, lead identification new targets treat malignancies.

Язык: Английский

An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry DOI Creative Commons
Elizabeth N. Wallace,

Connor A. West,

Colin T. McDowell

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 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.

Язык: Английский

Процитировано

37

Biosensor-based methods for exosome detection with applications to disease diagnosis DOI

Weikang Ge,

Zheying Mu,

Shiao Yang

и другие.

Biosensors and Bioelectronics, Год журнала: 2025, Номер unknown, С. 117362 - 117362

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1

The Role of IgLON Cell Adhesion Molecules in Neurodegenerative Diseases DOI Open Access
Marco Salluzzo,

Clara Vianello,

Sandra Abdullatef

и другие.

Genes, Год журнала: 2023, Номер 14(10), С. 1886 - 1886

Опубликована: Сен. 28, 2023

In the brain, cell adhesion molecules (CAMs) are critical for neurite outgrowth, axonal fasciculation, neuronal survival and migration, synapse formation maintenance. Among CAMs, IgLON family comprises five members: Opioid Binding Protein/Cell Adhesion Molecule Like (OPCML or OBCAM), Limbic System Associated Membrane Protein (LSAMP), neurotrimin (NTM), Neuronal Growth Regulator 1 (NEGR1), IgLON5. IgLONs exhibit three N-terminal C2 immunoglobulin domains; several glycosylation sites; a glycosylphosphatidylinositol anchoring to membrane. Interactions as homo- heterodimers in cis trans, well binding other molecules, appear their functions. Shedding by metalloproteases generates soluble factors interacting with cellular receptors activating signal transduction. The aim of this review was analyse available data implicating role neuropsychiatric disorders. Starting from identification pathological antibodies against IgLON5 an autoimmune neurodegenerative disease poorly understood mechanism action, accumulating evidence links disorders, albeit still undefined mechanisms which will require future thorough investigations.

Язык: Английский

Процитировано

13

Blood N-glycomics reveals individuals at risk for cognitive decline and Alzheimer’s disease DOI Creative Commons
Robin Ziyue Zhou, Stefan Gaunitz, Bjørn‐Eivind Kirsebom

и другие.

EBioMedicine, Год журнала: 2025, Номер 113, С. 105598 - 105598

Опубликована: Фев. 20, 2025

Язык: Английский

Процитировано

0

Morphological and Molecular Characteristics of Perineuronal Nets in the Human Prefrontal Cortex—A Possible Link to Microcircuitry Specialization DOI Creative Commons
Ivan Banovac,

Matija Vid Prkačin,

Ivona Kirchbaum

и другие.

Molecular Neurobiology, Год журнала: 2024, Номер unknown

Опубликована: Июль 3, 2024

Perineuronal nets (PNNs) are a type of extracellular matrix (ECM) that play significant role in synaptic activity and plasticity interneurons health disease. We researched PNNs' regional laminar representation molecular composition using immunohistochemistry transcriptome analysis Brodmann areas (BA) 9, 14r, 24 25 human postmortem brains aged 13-82 years. The numbers VCAN- NCAN-expressing PNNs, relative to the total number neurons, were highest cortical layers I VI while WFA-binding (WFA

Язык: Английский

Процитировано

3

Distinct spatial N‐glycan profiles reveal glioblastoma‐specific signatures DOI

Aaron O. Angerstein,

Lyndsay E.A. Young, Thatchawan Thanasupawat

и другие.

The Journal of Pathology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 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.

Язык: Английский

Процитировано

0

A personalized metabolic modelling approach through integrated analysis of RNA-Seq-based genomic variants and gene expression levels in Alzheimer’s disease DOI Creative Commons
Dilara Uzuner, Atılay İlgün, Fatma Betül Bozkurt

и другие.

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Март 27, 2025

Generating condition-specific metabolic models by mapping gene expression data to genome-scale (GEMs) is a routine approach elucidate disease mechanisms from perspective. On the other hand, integrating variants that perturb enzyme functionality same RNA-seq may enhance GEM accuracy, offering insights into genome-wide pathology. Our study pioneers extraction of both transcriptomic and genomic reconstruct personalized models. We map genes with significantly higher load pathogenic in Alzheimer's (AD) onto human together data. Comparative analysis resulting patient control shows enhanced accuracy detecting AD-associated pathways compared case where only mapped on GEM. Besides, several otherwise would-be missed are annotated AD considering effect variants. The authors used iMAT algorithm associated Disease (GEMs).

Язык: Английский

Процитировано

0

Integration of RNAseq transcriptomics and N-glycomics reveal biosynthetic pathways and predict structure-specific N-glycan expression DOI Creative Commons
Michael Russelle Alvarez,

Xavier A. Holmes,

Armin Oloumi

и другие.

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

glycoPATH integrates RNAseq transcriptomic and LC-MS/MS glycomic data, providing a platform to identify genes implicated in diseases involving N -glycan biosynthesis enabling the development of targeted therapeutics for these pathways.

Язык: Английский

Процитировано

0

Sweet Aging: Glycocalyx and Galectins in CNS Aging and Neurodegenerative Disorders DOI Open Access

Mohd Yaqub Mir,

Ádám Légrádi

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(10), С. 4699 - 4699

Опубликована: Май 14, 2025

Aging and aging-related neurodegenerative disorders, such as Alzheimer's disease, are characterized by chronic inflammation that progressively damages nervous tissue within the central system (CNS). In addition to cytokines, lectin-like carbohydrate recognition molecules play a critical role in modifying cellular communication during inflammation. Among these, galectins-particularly anti-inflammatory galectin-1 pro-inflammatory galectin-3-stand out due their immunological functions specificity for N-acetyllactosamine structures. Almost every cell type CNS can express recognize galectins, influencing various essential functions. N-acetyllactosamines, ligand structures recognized found beneath sialylated termini protein-linked oligosaccharides. During aging, oligosaccharide become shorter, exposing N-acetyllactosamines on protein surfaces, which enhances availability binding sites galectins. Genomic studies indicate number of galectin-1- galectin-3-expressing microglial cells increases with age- or age-related disease (Alzheimer's disease), reflecting an aging-associated rise galectin concentrations CNS. This increase parallels free N-acetyllactosamine-like ligands, suggesting galectin-N-acetyllactosamine interactions gain prominence more significant disorders. Understanding these molecular implications offers potential avenues targeted therapeutic strategies combating neurodegeneration.

Язык: Английский

Процитировано

0

Augmented doubly robust post-imputation inference for proteomic data DOI

Haeun Moon,

Jin‐Hong Du, Jing Lei

и другие.

The Annals of Applied Statistics, Год журнала: 2025, Номер 19(2)

Опубликована: Май 28, 2025

Язык: Английский

Процитировано

0