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dc.contributor.authorJokubaitis, VG
dc.contributor.authorGresle, MM
dc.contributor.authorKemper, DA
dc.contributor.authorDoherty, W
dc.contributor.authorPerreau, VM
dc.contributor.authorCipriani, TL
dc.contributor.authorJonas, A
dc.contributor.authorShaw, G
dc.contributor.authorKuhlmann, T
dc.contributor.authorKilpatrick, TJ
dc.contributor.authorButzkueven, H
dc.date.available2015-02-10T01:06:03Z
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.available2013-06-18
dc.date.issued2013-01-01
dc.identifierpii: 2051-5960-1-32
dc.identifier.citationJokubaitis, V. G., Gresle, M. M., Kemper, D. A., Doherty, W., Perreau, V. M., Cipriani, T. L., Jonas, A., Shaw, G., Kuhlmann, T., Kilpatrick, T. J. & Butzkueven, H. (2013). Endogenously regulated Dab2 worsens inflammatory injury in experimental autoimmune encephalomyelitis. ACTA NEUROPATHOLOGICA COMMUNICATIONS, 1 (1), https://doi.org/10.1186/2051-5960-1-32.
dc.identifier.issn2051-5960
dc.identifier.urihttp://hdl.handle.net/11343/45229
dc.description.abstractBACKGROUND: Neuroinflammation regulates both disease pathogenesis and repair in multiple sclerosis. In early multiple sclerosis lesion development, neuroinflammation causes demyelination and axonal injury, the likely final common determinant of disability. Here we report the identification of a novel neuroinflammatory mediator, Disabled-2 (Dab2). Dab2 is an intracellular adaptor protein with previously unknown function in the central nervous system. RESULTS: We report that Dab2 is up-regulated in lesional macrophages/microglia in the spinal cord in murine experimental autoimmune encephalomyelitis, a model of multiple sclerosis. We demonstrate that dab2 expression is positively correlated with experimental autoimmune encephalomyelitis disease severity during the acute disease phase. Furthermore, dab2-deficient mice have a less severe experimental autoimmune encephalomyelitis disease course and suffer less neuroinflammation and less axonal injury than their wild-type littermates. We demonstrate that dab2 expression is strongly associated with the expression of inducible nitric oxide synthase. We further demonstrate that Dab2 is expressed at the protein level by macrophages in early acute human multiple sclerosis lesions and that this correlates with axonal injury. CONCLUSIONS: Together, these results suggest that endogenous Dab2 exacerbates central nervous system inflammation, potentially acting to up-regulate reactive oxygen species expression in macrophages and microglia, and that it is of potential pathogenic relevance in Multiple Sclerosis.
dc.languageEnglish
dc.publisherBIOMED CENTRAL LTD
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleEndogenously regulated Dab2 worsens inflammatory injury in experimental autoimmune encephalomyelitis
dc.typeJournal Article
dc.identifier.doi10.1186/2051-5960-1-32
melbourne.affiliation.departmentFlorey Department of Neuroscience and Mental Health
melbourne.affiliation.departmentMedicine, Dentistry & Health Sciences
melbourne.affiliation.departmentCentre for Neuroscience
melbourne.affiliation.departmentMedicine (RMH)
melbourne.source.titleActa Neuropathologica Communications
melbourne.source.volume1
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid584579
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893401
melbourne.contributor.authorJokubaitis, Vilija
melbourne.contributor.authorGresle, Melissa
melbourne.contributor.authorKEMPER, DENNIS
melbourne.contributor.authorDOHERTY, WILLIAM
melbourne.contributor.authorPerreau, Victoria
melbourne.contributor.authorKilpatrick, Trevor
melbourne.contributor.authorButzkueven, Helmut
melbourne.contributor.authorCIPRIANI, TANIA
melbourne.contributor.authorJONAS, ANNA
dc.identifier.eissn2051-5960
melbourne.accessrightsOpen Access


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