Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation
Multiple Sclerosis, a chronic inflammatory demyelinating disease of the central nervous system, involves an increased expression of monocyte chemotactic protein 1 MCP1-/CCL2. For exerting its chemotactic effects, chemokine binding to glycosaminoglycans (GAGs) is required and therefore this interacti...
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Elsevier
2016
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| Online Access: | https://eprints.nottingham.ac.uk/46751/ |
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| author | Gschwandtner, Martha Piccinini, Anna Maria Geriza, Tanja Adage, Tiziana Kungl, Andreas |
| author_facet | Gschwandtner, Martha Piccinini, Anna Maria Geriza, Tanja Adage, Tiziana Kungl, Andreas |
| author_sort | Gschwandtner, Martha |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Multiple Sclerosis, a chronic inflammatory demyelinating disease of the central nervous system, involves an increased expression of monocyte chemotactic protein 1 MCP1-/CCL2. For exerting its chemotactic effects, chemokine binding to glycosaminoglycans (GAGs) is required and therefore this interaction represents a potential target for therapeutic intervention. We have designed an anti inflammatory decoy variant, Met-CCL2 (Y13AS21K Q23R), embodying increased affinity for GAGs as well as knocked out GPCR activation properties. This non-signalling dominant-negative mutant is shown here to be able to displace wild type CCL2 from GAGs by which it is supposed to interfere with the chemokine-related inflammatory response. In vivo, the anti-inflammatory properties were successfully demonstrated in a murine model of zymosan-induced peritonitis as well as in an experimental autoimmune encephalomyelitis, a model relevant for multiple sclerosis, where the compound lead to significantly reduced clinical scores due to reduction of cellular infiltrates and demyelination in spinal cord and cerebellum. These findings indicate a promising potential for future therapeutic development. |
| first_indexed | 2025-11-14T20:03:09Z |
| format | Article |
| id | nottingham-46751 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:03:09Z |
| publishDate | 2016 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-467512020-05-04T17:59:12Z https://eprints.nottingham.ac.uk/46751/ Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation Gschwandtner, Martha Piccinini, Anna Maria Geriza, Tanja Adage, Tiziana Kungl, Andreas Multiple Sclerosis, a chronic inflammatory demyelinating disease of the central nervous system, involves an increased expression of monocyte chemotactic protein 1 MCP1-/CCL2. For exerting its chemotactic effects, chemokine binding to glycosaminoglycans (GAGs) is required and therefore this interaction represents a potential target for therapeutic intervention. We have designed an anti inflammatory decoy variant, Met-CCL2 (Y13AS21K Q23R), embodying increased affinity for GAGs as well as knocked out GPCR activation properties. This non-signalling dominant-negative mutant is shown here to be able to displace wild type CCL2 from GAGs by which it is supposed to interfere with the chemokine-related inflammatory response. In vivo, the anti-inflammatory properties were successfully demonstrated in a murine model of zymosan-induced peritonitis as well as in an experimental autoimmune encephalomyelitis, a model relevant for multiple sclerosis, where the compound lead to significantly reduced clinical scores due to reduction of cellular infiltrates and demyelination in spinal cord and cerebellum. These findings indicate a promising potential for future therapeutic development. Elsevier 2016-07-28 Article PeerReviewed Gschwandtner, Martha, Piccinini, Anna Maria, Geriza, Tanja, Adage, Tiziana and Kungl, Andreas (2016) Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation. Neuroscience Letters, 626 . pp. 164-173. ISSN 1872-7972 CCL2 decoy Glycosaminoglycans Anti-inflammatory Multiple sclerosis Experimental autoimmune encephalomyelitis http://www.sciencedirect.com/science/article/pii/S0304394016303494 doi:10.1016/j.neulet.2016.05.037 doi:10.1016/j.neulet.2016.05.037 |
| spellingShingle | CCL2 decoy Glycosaminoglycans Anti-inflammatory Multiple sclerosis Experimental autoimmune encephalomyelitis Gschwandtner, Martha Piccinini, Anna Maria Geriza, Tanja Adage, Tiziana Kungl, Andreas Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation |
| title | Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation |
| title_full | Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation |
| title_fullStr | Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation |
| title_full_unstemmed | Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation |
| title_short | Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation |
| title_sort | interfering with the ccl2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation |
| topic | CCL2 decoy Glycosaminoglycans Anti-inflammatory Multiple sclerosis Experimental autoimmune encephalomyelitis |
| url | https://eprints.nottingham.ac.uk/46751/ https://eprints.nottingham.ac.uk/46751/ https://eprints.nottingham.ac.uk/46751/ |