Global view of human protein glycosylation pathways and functions

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 21(12), P. 729 - 749

Published: Oct. 21, 2020

Language: Английский

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Small RNAs are modified with N-glycans and displayed on the surface of living cells

Cell, Journal Year: 2021, Volume and Issue: 184(12), P. 3109 - 3124.e22

Published: May 17, 2021

Language: Английский

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Carbohydrate-Based Macromolecular Biomaterials

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(18), P. 10950 - 11029

Published: Aug. 2, 2021

Carbohydrates are the most abundant and one of important biomacromolecules in Nature. Except for energy-related compounds, carbohydrates can be roughly divided into two categories: as matter information. As matter, abundantly present extracellular matrix animals cell walls various plants, bacteria, fungi, etc., serving scaffolds. Some commonly found polysaccharides featured biocompatible materials with controllable rigidity functionality, forming polymeric biomaterials which widely used drug delivery, tissue engineering, etc. information, usually referred to glycans from glycoproteins, glycolipids, proteoglycans, bind proteins or other carbohydrates, thereby meditating cell–cell cell–matrix interactions. These could simplified synthetic glycopolymers, afforded through polymerization, multistep synthesis, a semisynthetic strategy. The information role demonstrated not only targeting reagents but also immune antigens adjuvants. latter included this review they always macromolecular formulation. In review, we intend provide relatively comprehensive summary carbohydrate-based since 2010 while emphasizing fundamental understanding guide rational design biomaterials. Carbohydrate-based macromolecules on basis their resources chemical structures will discussed, including naturally occurring polysaccharides, derived glycopolymers/glycodendrimers, supramolecular glycolipids/glycoproteins. Multiscale structure–function relationships several major application areas, delivery systems, immunology, detailed. We hope valuable development build bridge between promote new biomaterial near future.

Language: Английский

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Sialoglycans and Siglecs Can Shape the Tumor Immune Microenvironment

Trends in Immunology, Journal Year: 2020, Volume and Issue: 41(4), P. 274 - 285

Published: March 2, 2020

Language: Английский

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The role of innate immune genes in Alzheimer's disease

Current Opinion in Neurology, Journal Year: 2021, Volume and Issue: 34(2), P. 228 - 236

Published: Feb. 3, 2021

Purpose of review The aim this study was to provide an update on the role innate immune system and neuroinflammation in pathogenesis Alzheimer's disease, with emphasis microglial receptors CD33 TREM2. Recent findings Genome-wide association studies (GWAS) have identified many disease risk genes related response microglia including phagocytic TREM2 . GWAS pathway analyses emphasize crucial disease. Disease-associated been characterized by TREM2-dependent upregulation lipid metabolism genes. Impaired phagocytosis results amyloid beta (Aβ) accumulation leading that is primary cause neurodegeneration. modulate emerged as therapeutic targets Progress has made inhibit gene therapy, small molecules or immunotherapy, increase activity immunotherapy. Finally, mAbs against entered clinical trials may reduce brain. Summary Targeting via inhibition and/or activation important implications for neurodegeneration be addition monoclonal anti-Aβ antibody treatments remove plaques without reducing neuroinflammation.

Language: Английский

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Probing the binding specificities of human Siglecs by cell-based glycan arrays

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(17)

Published: April 23, 2021

Significance Siglecs are immunomodulatory receptors that recognize sialic acid–carrying glycans with important functions in immunity. However, many of their natural ligands poorly defined. We generated a cell-based glycan array comprised library isogenic human cells displaying the greater complexity acids on diverse structures and glycoconjugates context cell surface. applied this to reveal fine binding specificities for sialoglycans, informed underlying required glycosyltransferase genes, provided evidence selective by presentation distinct protein sequences. Insight into will advance understanding biological benefit therapeutic targeting autoimmunity, inflammation, cancer, Alzheimer’s disease.

Language: Английский

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Targeting cancer glycosylation repolarizes tumor-associated macrophages allowing effective immune checkpoint blockade

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(669)

Published: Nov. 2, 2022

Immune checkpoint blockade (ICB) has substantially improved the prognosis of patients with cancer, but majority experiences limited benefit, supporting need for new therapeutic approaches. Up-regulation sialic acid–containing glycans, termed hypersialylation, is a common feature cancer-associated glycosylation, driving disease progression and immune escape through engagement Siglec receptors on tumor-infiltrating cells. Here, we show that tumor sialylation correlates distinct states reduced survival in human cancers. The targeted removal ligands microenvironment, using an antibody-sialidase conjugate, enhanced antitumor immunity halted several murine models. Using single-cell RNA sequencing, revealed desialylation repolarized tumor-associated macrophages (TAMs). We also identified Siglec-E as main receptor hypersialylation TAMs. Last, found genetic desialylation, well loss Siglec-E, efficacy ICB. Thus, represents immunotherapeutic approach to reshape macrophage phenotypes augment adaptive response.

Language: Английский

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Tumor microenvironment signaling and therapeutics in cancer progression

Cancer Communications, Journal Year: 2023, Volume and Issue: 43(5), P. 525 - 561

Published: April 2, 2023

Abstract Tumor development and metastasis are facilitated by the complex interactions between cancer cells their microenvironment, which comprises stromal extracellular matrix (ECM) components, among other factors. Stromal can adopt new phenotypes to promote tumor cell invasion. A deep understanding of signaling pathways involved in cell‐to‐cell cell‐to‐ECM is needed design effective intervention strategies that might interrupt these interactions. In this review, we describe microenvironment (TME) components associated therapeutics. We discuss clinical advances prevalent newly discovered TME, immune checkpoints immunosuppressive chemokines, currently used inhibitors targeting pathways. These include both intrinsic non‐autonomous TME: protein kinase C (PKC) signaling, Notch, transforming growth factor (TGF‐β) Endoplasmic Reticulum (ER) stress response, lactate Metabolic reprogramming, cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) Siglec also recent Programmed Cell Death Protein 1 (PD‐1), Cytotoxic T‐Lymphocyte Associated 4 (CTLA4), T‐cell immunoglobulin mucin‐3 (TIM‐3) Lymphocyte Activating Gene 3 (LAG3) checkpoint along with C‐C chemokine receptor (CCR4)‐ class chemokines 22 (CCL22)/ 17 (CCL17), type 2 (CCR2)‐ (C‐C motif) ligand (CCL2), 5 (CCR5)‐ (CCL3) axis TME. addition, review provides a holistic TME as three‐dimensional microfluidic models believed recapitulate original characteristics patient hence may be platform study mechanisms screen for various anti‐cancer therapies. further systemic influences gut microbiota reprogramming treatment response. Overall, comprehensive analysis diverse most critical highlighting newest preclinical studies underlying biology. highlight importance technologies microfluidics lab‐on‐chip research present an overview extrinsic factors, such inhabitant human microbiome, have potential modulate biology drug responses.

Language: Английский

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Glycoconjugates: Synthesis, Functional Studies, and Therapeutic Developments

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(20), P. 15603 - 15671

Published: Sept. 29, 2022

Glycoconjugates are major constituents of mammalian cells that formed via covalent conjugation carbohydrates to other biomolecules like proteins and lipids often expressed on the cell surfaces. Among three classes glycoconjugates, proteoglycans glycoproteins contain glycans linked protein backbone amino acid residues such as Asn for N-linked Ser/Thr O-linked glycans. In glycolipids, a lipid component glycerol, polyisoprenyl pyrophosphate, fatty ester, or sphingolipid. Recently, glycoconjugates have become better structurally defined biosynthetically understood, especially those associated with human diseases, accessible new drug, diagnostic, therapeutic developments. This review describes status advances in biological study applications natural synthetic including proteoglycans, glycoproteins, glycolipids. The scope, limitations, novel methodologies synthesis clinical development vaccines, glyco-remodeled antibodies, glycan-based adjuvants, glycan-specific receptor-mediated drug delivery platforms, etc., their future prospectus discussed.

Language: Английский

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Global functions of O‐glycosylation: promises and challenges in O‐glycobiology

FEBS Journal, Journal Year: 2021, Volume and Issue: 288(24), P. 7183 - 7212

Published: Aug. 4, 2021

Mucin type O‐glycosylation is one of the most diverse types glycosylation, playing essential roles in tissue development and homeostasis. In complex organisms, O‐GalNAc glycans comprise a substantial proportion glycocalyx, with defined functions hemostatic, gastrointestinal, respiratory systems. Furthermore, are important players host–microbe interactions, changes O‐glycan composition associated certain diseases metabolic conditions, which some instances can be used for diagnosis or therapeutic intervention. Breakthroughs O‐glycobiology have gone hand new technologies, such as advancements mass spectrometry, well facilitation genetic engineering mammalian cell lines. High‐throughput O‐glycoproteomics enabled us to draw comprehensive map O‐glycosylation, mining this information has supported definition confirmation related site‐specific O‐glycans. This includes protection from proteolytic cleavage, modulation binding affinity receptor function. Yet, there still much discover, among next challenges will define context‐dependent O‐glycans different stages cellular differentiation, metabolism, host–microbiome disease. review, we present achievements promises glycobiology driven by technological advances analytical methods, engineering, systems biology.

Language: Английский

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