@article { , title = {Interfering with the CCL2-glycosaminoglycan axis as a potential approach to modulate neuroinflammation}, abstract = {© 2016 Elsevier Ireland Ltd. 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 (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.}, doi = {10.1016/j.neulet.2016.05.037}, eissn = {1872-7972}, issn = {0304-3940}, journal = {Neuroscience Letters}, pages = {164-173}, publicationstatus = {Published}, publisher = {Elsevier}, url = {https://nottingham-repository.worktribe.com/output/798633}, volume = {626}, keyword = {CCL2 decoy, Glycosaminoglycans, Anti-inflammatory, Multiple sclerosis, Experimental autoimmune encephalomyelitis}, year = {2016}, author = {Gschwandtner, Martha and Piccinini, Anna Maria and Geriza, Tanja and Adage, Tiziana and Kungl, Andreas} }