ArticleActa neuropathologica communications2013
Endogenously regulated Dab2 worsens inflammatory injury in experimental autoimmune encephalomyelitis.
Article in Acta neuropathologica communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 35 citations in OpenAlex.
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- Pediatric glioma immune profiling identifies TIM3 as a therapeutic target in BRAF fusion pilocytic astrocytoma.The Journal of clinical investigation · 2024Article
- Adaptor molecules mediate negative regulation of macrophage inflammatory pathways: a closer look.Frontiers in immunology · 2024Review
- Immune checkpoint blockade induces distinct alterations in the microenvironments of primary and metastatic brain tumors.The Journal of clinical investigation · 2023Article
- Disabled-2 (International journal of molecular sciences · 2022Review
- Chromosome-level genome and population genomics reveal evolutionary characteristics and conservation status of Chinese indigenous geese.Communications biology · 2022Article
- Matrine treatment reduces retinal ganglion cell apoptosis in experimental optic neuritis.Scientific reports · 2021Article
- BMSCs differentiated into neurons, astrocytes and oligodendrocytes alleviated the inflammation and demyelination of EAE mice models.PloS one · 2021Article
- Daphnetin Ameliorates Experimental Autoimmune Encephalomyelitis Through Regulating Heme Oxygenase-1.Neurochemical research · 2020Article
- Emerging Roles of Disabled Homolog 2 (DAB2) in Immune Regulation.Frontiers in immunology · 2020Review
- Matrine Treatment Blocks NogoA-Induced Neural Inhibitory Signaling Pathway in Ongoing Experimental Autoimmune Encephalomyelitis.Molecular neurobiology · 2017Article
- Tanshinone IIA attenuates experimental autoimmune encephalomyelitis in rats.Molecular medicine reports · 2016Article
- Disabled homolog 2 controls macrophage phenotypic polarization and adipose tissue inflammation.The Journal of clinical investigation · 2016Article
- Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice.Frontiers in cell and developmental biology · 2016Review
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeuroinflammation 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.
resultsWe 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.
conclusionsTogether, 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.
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