Polysialic Acid in the Immune System

Villanueva-Cabello, Tania M; Gutiérrez-Valenzuela, Lya D.; Salinas-Marín, Roberta; López-Guerrero, Delia Vanesa; Martínez-Duncker, Iván

doi:10.3389/fimmu.2021.823637

Cited by 24 publications

(25 citation statements)

References 230 publications

(243 reference statements)

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“…Moreover, CCL21, unlike CCL19, has a positively charged 32 amino acid C-terminal tail that allows for avid binding to cell surface glycosaminoglycans (GAGs). Additionally, efficient CCL21 signalling requires CCR7 to be polysialylated, a posttranslational modification that releases CCL21 from a tail-regulated auto-inhibitory conformation [ 1 , 15 , 16 , 17 ]. CCR7 signalling bias has been extensively studied in vitro.…”

Section: Introductionmentioning

confidence: 99%

Cellular Electrical Impedance as a Method to Decipher CCR7 Signalling and Biased Agonism

Vanalken

Boon

Doijen

et al. 2022

IJMS

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The human C-C chemokine receptor type 7 (CCR7) has two endogenous ligands, C-C chemokine ligand 19 (CCL19) and CCL21, displaying biased agonism reflected by a pronounced difference in the level of β-arrestin recruitment. Detecting this preferential activation generally requires the use of separate, pathway-specific label-based assays. In this study, we evaluated an alternative methodology to study CCR7 signalling. Cellular electrical impedance (CEI) is a label-free technology which yields a readout that reflects an integrated cellular response to ligand stimulation. CCR7-expressing HEK293 cells were stimulated with CCL19 or CCL21, which induced distinct impedance profiles with an apparent bias during the desensitisation phase of the response. This discrepancy was mainly modulated by differential β-arrestin recruitment, which shaped the impedance profile but did not seem to contribute to it directly. Pathway deconvolution revealed that Gαi-mediated signalling contributed most to the impedance profile, but Gαq- and Gα12/13-mediated pathways were also involved. To corroborate these results, label-based pathway-specific assays were performed. While CCL19 more potently induced β-arrestin2 recruitment and receptor internalisation than CCL21, both chemokines showed a similar level of Gαi protein activation. Altogether, these findings indicate that CEI is a powerful method to analyse receptor signalling and biased agonism.

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Section: Introductionmentioning

confidence: 99%

Cellular Electrical Impedance as a Method to Decipher CCR7 Signalling and Biased Agonism

Vanalken

Boon

Doijen

et al. 2022

IJMS

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“…Prospective longitudinal studies including measurements of polySia in cerebrospinal fluid will be necessary to further validate our findings and to further establish a causal relationship between polySia and SZ/SZA and BD. While evidence suggests cross-talk of polySia 30 , 36 , 49 , possibly via an active transport mechanism 11 , 12 , over the blood-CNS barrier, further studies are necessary to better quantify this cross-talk. We have not seen any significant effect of antipsychotic or antidepressant medication on the polySia serum level, but we are aware that this could be a potential confounder.…”

Section: Discussionmentioning

confidence: 99%

Association of polysialic acid serum levels with schizophrenia spectrum and bipolar disorder-related structural brain changes and hospitalization

Müller-Miny

Thiel

Meinert

et al. 2023

Sci Rep

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Expression of polysialic acid (polySia) in the adult brain is enriched in areas of continuous neurogenesis and plasticity such as the hippocampus. Genome-wide association studies identified variants of glycosylation enzyme-encoding genes, required for the generation of polySia, to be associated with the development of schizophrenia and bipolar disorder. Here, we report that serum levels of polySia are increased in patients with schizophrenia spectrum disorder compared to patients with major depressive disorders or demographically matched healthy controls. Furthermore, elevated polySia serum levels are associated with structural hippocampal gray matter decline in schizophrenia spectrum and bipolar disorder. In patients with schizophrenia spectrum disorder, polySia serum levels correlate with the number, duration of disease-related hospitalizations, early retirement and medical leave as estimators of detrimental long-term disease trajectories. Our data show that polySia serum levels are linked to structural hippocampal brain changes in schizophrenia spectrum and bipolar disorders, and suggest a contribution of polySia to the pathophysiology of these diseases.

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“…Nanoparticles decorated with sialic acid are therefore explored as a means to interfere with cancer progression . Nanoparticles are widely coated with single units of sialic acid or a polymeric version of sialic acid, α-2,8-linked sialic acids (Polysia), but true glycopolymers, where sialic acid is attached to the side chain of a synthetic polymer, has barely been explored. This opens opportunities as the synthesis of glycopolymers based on sialic acid has already been described in the literature, , but it has not yet been linked with cancer treatment.…”

Section: What Carbohydrates Have Been Used For Therapeutic Drug Deliv...mentioning

confidence: 99%

Glycopolymers for Drug Delivery: Opportunities and Challenges

Stenzel

2022

Macromolecules

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Glycopolymers are synthetic polymers with pendant sugars, which hold promise for a range of biomedical applications ranging from tissue engineering to sensing. The known specific interaction of glycopolymers with lectins has inspired researchers to use these polymers to deliver drugs to cells that overexpress lectin receptors. As a result, many glycopolymersbased on mannose, galactose, fructose, or other saccharides−have been used for the targeted delivery of drugs, ranging from traditional anticancer drugs to nucleic acid-derived therapeutics. For drug delivery purposes, glycopolymers are typically processed into nanoparticles that form a matrix to entrap the drug safely, such as micelles, polyplexes, polyion complex micelles, or other nanosized carriers. In vitro and in vivo studies have shown that drugs can indeed be delivered selectively to specific cells by leveraging the selective recognition of surface bound lectins. The key to the interaction between glycopolymers and lectins is the presence of strong intermolecular forces such as hydrogen bonding. The formation of strong hydrogen bonds can, however, also be one of the drawbacks of these materials. Glycopolymers tend to self-aggregate, they interact with drugs in unexpected ways, or they bind proteins in a nonspecific manner. Despite these challenges, nanoparticles based on glycopolymers might offer possibilities that cannot be replicated by other watersoluble polymers. They have already shown that they can effectively deliver drugs in vivo, though more preclinical studies are necessary to enable their broader clinical uptake. Further focus could be directed at an improved understanding of the interface between glycopolymers and the biological surrounding as a key to improve the targeting ability of these nanoparticles in vivo. In this Perspective, I will discuss the aspects to consider when preparing drug delivery carrier using glycopolymers. This will include the interaction of the glyconanoparticles with the drug and the resulting property changes, the types of glycopolymers suitable for drug delivery, the effect of the nanoparticle structure on the affinity to cell surface bound lectins or GLUT transporters and the promising in vivo results that show selective delivery.

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Polysialic Acid in the Immune System

Cited by 24 publications

References 230 publications

Cellular Electrical Impedance as a Method to Decipher CCR7 Signalling and Biased Agonism

Cellular Electrical Impedance as a Method to Decipher CCR7 Signalling and Biased Agonism

Association of polysialic acid serum levels with schizophrenia spectrum and bipolar disorder-related structural brain changes and hospitalization

Glycopolymers for Drug Delivery: Opportunities and Challenges

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