Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acheron, a Lupus antigen ortholog, was identified as a novel death-associated transcript from the intersegmental muscles of the moth Manduca sexta. Acheron is phylogenetically-conserved and represents a new sub-family of Lupus antigen proteins. Acheron is expressed predominantly in neurons and muscle in vertebrates, and regulates several developmental events including myogenesis, neurogenesis and possibly metastasis. Using Acheron as bait, we performed a yeast two-hybrid screen with a mouse embryo cDNA library and identified CASK-C, a novel CASK/Lin-2 isoform, as an Acheron binding partner. Acheron and CASK-C bind via the C-terminus of Acheron and the CaMKII-like domain of CASK-C. Co-immunoprecipitation assays verify this interaction and demonstrate that Acheron also forms a complex with all members of the Id (inhibitor of differentiation) proteins. Taken together, these data suggest a mechanism by which Acheron may regulate development and pathology.
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PMID:Acheron, an novel LA antigen family member, binds to CASK and forms a complex with Id transcription factors. 3053 60

Treatment of autoimmune diseases is still largely based on the use of systemically acting immunosuppressive drugs, which invariably cause severe side effects. Calcium/calmodulin-dependent protein kinase IV is involved in the suppression of IL-2 and the production of IL-17. Its pharmacologic or genetic inhibition limits autoimmune disease in mice. In this study, we demonstrate that KN93, a small-molecule inhibitor of calcium/calmodulin-dependent protein kinase IV, targeted to CD4(+) T cells via a nanolipogel delivery system, markedly reduced experimental autoimmune encephalomyelitis and was 10-fold more potent than the free systemically delivered drug in the lupus mouse models. The targeted delivery of KN93 did not deplete T cells but effectively blocked Th17 cell differentiation and expansion as measured in the spinal cords and kidneys of mice developing experimental autoimmune encephalomyelitis or lupus, respectively. These results highlight the promise of cell-targeted inhibition of molecules involved in the pathogenesis of autoimmunity as a means of advancing the treatment of autoimmune diseases.
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PMID:Cutting Edge: Nanogel-Based Delivery of an Inhibitor of CaMK4 to CD4+ T Cells Suppresses Experimental Autoimmune Encephalomyelitis and Lupus-like Disease in Mice. 2656 50

Calcium/calmodulin-dependent protein kinase IV (CaMK4) is a multifunctional serine/threonine kinase that regulates gene expression by activating transcription factors in a wide range of immune cells including T cells and antigen-presenting cells. The function of CaMK4 is suggested to be abnormal mainly in systemic lupus erythematosus (SLE), which is characterized by autoantibody production, immune complex formation, and immune dysregulation. Although accumulating evidence indicates that CaMK4 plays important roles in the immune responses, the precise molecular mechanisms underlying the development of autoimmune diseases and inflammatory disorders have not been established. In this review, we briefly summarize the role of CaMK4 in immune responses. We also discuss T-cell signaling pathways that control interleukin (IL)-17 production in patients with lupus nephritis and in glomerulonephritis in lupus-prone mice. A better understanding of the signaling and gene regulation of CaMK4 will lead to the identification of novel therapeutic targets in Th17 driven-autoimmune diseases.
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PMID:The role of CaMK4 in immune responses. 2925 71