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The Role of Glycosaminoglycans in Human Diseases
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The Role of Glycosaminoglycans in Human Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 9283

Special Issue Editor

Dr. Darko Kero

E-Mail Website
Guest Editor
Graduate Study of Dental Medicine, School of Medicine, University of Split, Šoltanska 2, HR-21000 Split, Croatia
Interests: glycosaminoglycans; syndecans; ECM; periodontitis; immunofluorescence; statistical modeling

Special Issue Information

Dear Colleagues,

Glycosaminoglycans are one of the most important components of the extracellular matrix. As modulators of cell signaling, glycosaminoglycans are involved in the regulation of several processes that are important for the development and homeostasis of bone tissues, including proliferation, differentiation, adhesion, and migration of cells. The role of glycosaminoglycans in the above processes depends on their biochemical structure and the way these molecules are incorporated into the extracellular matrix as free polysaccharide chains or covalently bound in complexes with corresponding protein carriers (proteoglycans, glycoproteins). Accordingly, the structure and overall expression of glycosaminoglycans are tissue-specific and subject to dynamic changes during pathological events in the tissue (inflammation, infection, healing, regeneration). Exploiting different aspects of glycosaminoglycan biology holds great promise for the treatment of various human diseases.

We are pleased to publish original scientific papers or reviews that address the role of glycosaminoglycans, enzymes for glycosaminoglycan biosynthesis, modification, and degradation, and cell surface receptors for glycosaminoglycans in the pathogenesis of human diseases including inflammatory diseases, infectious diseases and cancer. Scientific papers dealing with the development of novel synthetic derivatives or therapeutics based on glycosaminoglycans and related factors for the treatment of experimental models (cell cultures, animal preparations, humans) with biomolecular experiments are also welcome. Purely clinical studies on the topic will not be suitable for this Special Issue.

The Article Processing Charge for publication in this open access journal is CHF 2900 (Swiss Francs) but the authors of papers submitted by the deadline will enjoy a favorable discount.

I cordially invite you to submit a paper to this Special Issue titled: “The Role of Glycosaminoglycans in Human Diseases”. Please, feel free to forward this invitation to your team members or colleagues who may also be interested in the topic.

Dr. Darko Kero
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glycosaminoglycans
  • inflammation
  • infectious disease
  • cancer

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Published Papers (4 papers)

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Research

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15 pages, 7743 KiB  
Article
CANT1 Is Involved in Collagen Fibrogenesis in Tendons by Regulating the Synthesis of Dermatan/Chondroitin Sulfate Attached to the Decorin Core Protein
by Rina Yamashita, Saki Tsutsui, Shuji Mizumoto, Takafumi Watanabe, Noritaka Yamamoto, Kenta Nakano, Shuhei Yamada, Tadashi Okamura and Tatsuya Furuichi
Int. J. Mol. Sci. 2025, 26(6), 2463; https://doi.org/10.3390/ijms26062463 - 10 Mar 2025
Viewed by 550
Abstract
Tendons are connective tissues that join muscles and bones and are rich in glycosaminoglycans (GAGs). Decorin is a proteoglycan with one dermatan sulfate (DS) or chondroitin sulfate (CS) chain (a type of GAG) attached to its core protein and is involved in regulating [...] Read more.
Tendons are connective tissues that join muscles and bones and are rich in glycosaminoglycans (GAGs). Decorin is a proteoglycan with one dermatan sulfate (DS) or chondroitin sulfate (CS) chain (a type of GAG) attached to its core protein and is involved in regulating the assembly of collagen fibrils in the tendon extracellular matrix (ECM). Calcium-activated nucleotidase 1 (CANT1), a nucleotidase that hydrolyzes uridine diphosphate into uridine monophosphate and phosphate, plays an important role in GAG synthesis in cartilage. In the present study, we performed detailed histological and biochemical analyses of the tendons from Cant1 knockout (Cant1−/−) mice. No abnormalities were observed in the tendons on postnatal day 1 (P1); however, remarkable hypoplasia was observed on P30 and P180. The collagen fibrils were more angular and larger in the Cant1−/− tendons than in the control (Ctrl) tendons. In the Cant1−/− tendons, the DS/CS content was significantly reduced, and the DC/CS chains attached to the decorin core protein became shorter than those in the Ctrl tendons. No abnormalities were observed in the proliferation and differentiation of tendon fibroblasts (tenocytes) in the Cant1−/− mice. These results strongly suggest that CANT1 dysfunction causes defective DS/CS synthesis, followed by impairment of decorin function, which regulates collagen fibrogenesis in the tendon ECM. Multiple joint dislocations are a clinical feature of Desbuquois dysplasia type 1 caused by human CANT1 mutations. The multiple joint dislocations associated with this genetic disorder may be attributed to tendon fragility resulting from CANT1 dysfunction. Full article
(This article belongs to the Special Issue The Role of Glycosaminoglycans in Human Diseases)
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23 pages, 10151 KiB  
Article
Vascular Heparan Sulfate and Amyloid-β in Alzheimer’s Disease Patients
by Ilayda Ozsan McMillan, Marla Gearing and Lianchun Wang
Int. J. Mol. Sci. 2024, 25(7), 3964; https://doi.org/10.3390/ijms25073964 - 2 Apr 2024
Cited by 2 | Viewed by 1836
Abstract
Alzheimer’s disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of extracellular amyloid-β peptides (Aβ) within the cerebral parenchyma and vasculature, which is known as cerebral amyloid angiopathy (CAA). This study utilized confocal imaging to investigate heparan sulfate (HS) expression within [...] Read more.
Alzheimer’s disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of extracellular amyloid-β peptides (Aβ) within the cerebral parenchyma and vasculature, which is known as cerebral amyloid angiopathy (CAA). This study utilized confocal imaging to investigate heparan sulfate (HS) expression within the cerebrovasculature and its associations with Aβ, gender, and ApoE4 genotype in AD. Our investigation revealed elevated levels of HS in the cerebrovasculature of AD patients with severe CAA. Additionally, these patients exhibited higher HS colocalization with Aβ in the cerebrovasculature, including both endothelial and vascular smooth muscle cell compartments. Intriguingly, a reversal in the polarized expression of HS within the cerebrovasculature was detected in AD patients with severe CAA. Furthermore, male patients exhibited lower levels of both parenchymal and cerebrovascular HS. Additionally, ApoE4 carriers displayed heightened cerebrovascular Aβ expression and a tendency of elevated cerebrovascular HS levels in AD patients with severe CAA. Overall, these findings reveal potential intricate interplay between HS, Aβ, ApoE, and vascular pathology in AD, thereby underscoring the potential roles of cerebrovascular HS in CAA development and AD pathology. Further study of the underlying mechanisms may present novel therapeutic avenues for AD treatment. Full article
(This article belongs to the Special Issue The Role of Glycosaminoglycans in Human Diseases)
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Review

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48 pages, 4744 KiB  
Review
Glycosaminoglycans, Instructive Biomolecules That Regulate Cellular Activity and Synaptic Neuronal Control of Specific Tissue Functional Properties
by James Melrose
Int. J. Mol. Sci. 2025, 26(6), 2554; https://doi.org/10.3390/ijms26062554 - 12 Mar 2025
Viewed by 756
Abstract
Glycosaminoglycans (GAGs) are a diverse family of ancient biomolecules that evolved over millennia as key components in the glycocalyx that surrounds all cells. GAGs have molecular recognition and cell instructive properties when attached to cell surface and extracellular matrix (ECM) proteoglycans (PGs), which [...] Read more.
Glycosaminoglycans (GAGs) are a diverse family of ancient biomolecules that evolved over millennia as key components in the glycocalyx that surrounds all cells. GAGs have molecular recognition and cell instructive properties when attached to cell surface and extracellular matrix (ECM) proteoglycans (PGs), which act as effector molecules that regulate cellular behavior. The perception of mechanical cues which arise from perturbations in the ECM microenvironment allow the cell to undertake appropriate biosynthetic responses to maintain ECM composition and tissue function. ECM PGs substituted with GAGs provide structural support to weight-bearing tissues and an ability to withstand shear forces in some tissue contexts. This review outlines the structural complexity of GAGs and the diverse functional properties they convey to cellular and ECM PGs. PGs have important roles in cartilaginous weight-bearing tissues and fibrocartilages subject to tension and high shear forces and also have important roles in vascular and neural tissues. Specific PGs have roles in synaptic stabilization and convey specificity and plasticity in the regulation of neurophysiological responses in the CNS/PNS that control tissue function. A better understanding of GAG instructional roles over cellular behavior may be insightful for the development of GAG-based biotherapeutics designed to treat tissue dysfunction in disease processes and in novel tissue repair strategies following trauma. GAGs have a significant level of sophistication over the control of cellular behavior in many tissue contexts, which needs to be fully deciphered in order to achieve a useful therapeutic product. GAG biotherapeutics offers exciting opportunities in the modern glycomics arena. Full article
(This article belongs to the Special Issue The Role of Glycosaminoglycans in Human Diseases)
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41 pages, 2245 KiB  
Review
The Glycosaminoglycan Side Chains and Modular Core Proteins of Heparan Sulphate Proteoglycans and the Varied Ways They Provide Tissue Protection by Regulating Physiological Processes and Cellular Behaviour
by Brooke L. Farrugia and James Melrose
Int. J. Mol. Sci. 2023, 24(18), 14101; https://doi.org/10.3390/ijms241814101 - 14 Sep 2023
Cited by 14 | Viewed by 4514
Abstract
This review examines the roles of HS–proteoglycans (HS–PGs) in general, and, in particular, perlecan and syndecan as representative examples and their interactive ligands, which regulate physiological processes and cellular behavior in health and disease. HS–PGs are essential for the functional properties of tissues [...] Read more.
This review examines the roles of HS–proteoglycans (HS–PGs) in general, and, in particular, perlecan and syndecan as representative examples and their interactive ligands, which regulate physiological processes and cellular behavior in health and disease. HS–PGs are essential for the functional properties of tissues both in development and in the extracellular matrix (ECM) remodeling that occurs in response to trauma or disease. HS–PGs interact with a biodiverse range of chemokines, chemokine receptors, protease inhibitors, and growth factors in immune regulation, inflammation, ECM stabilization, and tissue protection. Some cell regulatory proteoglycan receptors are dually modified hybrid HS/CS proteoglycans (betaglycan, CD47). Neurexins provide synaptic stabilization, plasticity, and specificity of interaction, promoting neurotransduction, neurogenesis, and differentiation. Ternary complexes of glypican-1 and Robbo–Slit neuroregulatory proteins direct axonogenesis and neural network formation. Specific neurexin–neuroligin complexes stabilize synaptic interactions and neural activity. Disruption in these interactions leads to neurological deficits in disorders of functional cognitive decline. Interactions with HS–PGs also promote or inhibit tumor development. Thus, HS–PGs have complex and diverse regulatory roles in the physiological processes that regulate cellular behavior and the functional properties of normal and pathological tissues. Specialized HS–PGs, such as the neurexins, pikachurin, and Eyes-shut, provide synaptic stabilization and specificity of neural transduction and also stabilize the axenome primary cilium of phototoreceptors and ribbon synapse interactions with bipolar neurons of retinal neural networks, which are essential in ocular vision. Pikachurin and Eyes–Shut interactions with an α-dystroglycan stabilize the photoreceptor synapse. Novel regulatory roles for HS–PGs controlling cell behavior and tissue function are expected to continue to be uncovered in this fascinating class of proteoglycan. Full article
(This article belongs to the Special Issue The Role of Glycosaminoglycans in Human Diseases)
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