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 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...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2016
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| _version_ | 1797063569449156608 |
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| author | Gschwandtner, M Piccinini, A Gerlza, T Adage, T Kungl, A |
| author_facet | Gschwandtner, M Piccinini, A Gerlza, T Adage, T Kungl, A |
| author_sort | Gschwandtner, M |
| collection | OXFORD |
| description | Multiple Sclerosis, a chronic inflammatory demyelinating disease of the central nervous system, involves 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 (Y13A S21K 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 | 2024-03-06T21:01:47Z |
| format | Journal article |
| id | oxford-uuid:3b1e2019-f98b-4b84-8ab7-ffbb95e6b43f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:01:47Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:3b1e2019-f98b-4b84-8ab7-ffbb95e6b43f2022-03-26T14:05:42ZInterfering with the CCL2-glycosaminoglycan axis as a potential approach to modulate neuroinflammationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3b1e2019-f98b-4b84-8ab7-ffbb95e6b43fEnglishSymplectic Elements at OxfordElsevier2016Gschwandtner, MPiccinini, AGerlza, TAdage, TKungl, AMultiple Sclerosis, a chronic inflammatory demyelinating disease of the central nervous system, involves 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 (Y13A S21K 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. |
| spellingShingle | Gschwandtner, M Piccinini, A Gerlza, T Adage, T Kungl, A 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 |
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