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Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond

Mammalian neuraminidases (NEUs), also known as sialidases, are enzymes that cleave off the terminal neuraminic, or sialic, acid resides from the carbohydrate moieties of glycolipids and glycoproteins. A rapidly growing body of literature indicates that in addition to their metabolic functions, NEUs...

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Autores principales: Lillehoj, Erik P., Luzina, Irina G., Atamas, Sergei P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035539/
https://www.ncbi.nlm.nih.gov/pubmed/35479093
http://dx.doi.org/10.3389/fimmu.2022.883079
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author Lillehoj, Erik P.
Luzina, Irina G.
Atamas, Sergei P.
author_facet Lillehoj, Erik P.
Luzina, Irina G.
Atamas, Sergei P.
author_sort Lillehoj, Erik P.
collection PubMed
description Mammalian neuraminidases (NEUs), also known as sialidases, are enzymes that cleave off the terminal neuraminic, or sialic, acid resides from the carbohydrate moieties of glycolipids and glycoproteins. A rapidly growing body of literature indicates that in addition to their metabolic functions, NEUs also regulate the activity of their glycoprotein targets. The simple post-translational modification of NEU protein targets—removal of the highly electronegative sialic acid—affects protein folding, alters protein interactions with their ligands, and exposes or covers proteolytic sites. Through such effects, NEUs regulate the downstream processes in which their glycoprotein targets participate. A major target of desialylation by NEUs are mucins (MUCs), and such post-translational modification contributes to regulation of disease processes. In this review, we focus on the regulatory roles of NEU-modified MUCs as coordinators of disease pathogenesis in fibrotic, inflammatory, infectious, and autoimmune diseases. Special attention is placed on the most abundant and best studied NEU1, and its recently discovered important target, mucin-1 (MUC1). The role of the NEU1 - MUC1 axis in disease pathogenesis is discussed, along with regulatory contributions from other MUCs and other pathophysiologically important NEU targets.
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spelling pubmed-90355392022-04-26 Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond Lillehoj, Erik P. Luzina, Irina G. Atamas, Sergei P. Front Immunol Immunology Mammalian neuraminidases (NEUs), also known as sialidases, are enzymes that cleave off the terminal neuraminic, or sialic, acid resides from the carbohydrate moieties of glycolipids and glycoproteins. A rapidly growing body of literature indicates that in addition to their metabolic functions, NEUs also regulate the activity of their glycoprotein targets. The simple post-translational modification of NEU protein targets—removal of the highly electronegative sialic acid—affects protein folding, alters protein interactions with their ligands, and exposes or covers proteolytic sites. Through such effects, NEUs regulate the downstream processes in which their glycoprotein targets participate. A major target of desialylation by NEUs are mucins (MUCs), and such post-translational modification contributes to regulation of disease processes. In this review, we focus on the regulatory roles of NEU-modified MUCs as coordinators of disease pathogenesis in fibrotic, inflammatory, infectious, and autoimmune diseases. Special attention is placed on the most abundant and best studied NEU1, and its recently discovered important target, mucin-1 (MUC1). The role of the NEU1 - MUC1 axis in disease pathogenesis is discussed, along with regulatory contributions from other MUCs and other pathophysiologically important NEU targets. Frontiers Media S.A. 2022-04-11 /pmc/articles/PMC9035539/ /pubmed/35479093 http://dx.doi.org/10.3389/fimmu.2022.883079 Text en Copyright © 2022 Lillehoj, Luzina and Atamas https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lillehoj, Erik P.
Luzina, Irina G.
Atamas, Sergei P.
Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond
title Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond
title_full Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond
title_fullStr Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond
title_full_unstemmed Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond
title_short Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond
title_sort mammalian neuraminidases in immune-mediated diseases: mucins and beyond
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035539/
https://www.ncbi.nlm.nih.gov/pubmed/35479093
http://dx.doi.org/10.3389/fimmu.2022.883079
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